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Sample records for achelis foundation bodman

  1. AChE for DNA degradation.

    PubMed

    Sánchez-Osuna, María; Yuste, Victor J

    2015-06-01

    DNA hydrolysis is a biochemical process often associated with different forms of cell death, including apoptosis. In a recent paper published in Cell Discovery, Du et al. report that synaptic acetylcholinesterase (AChE-S) shows an unexpected enzymatic activity as DNase switched on after cytotoxic insults. PMID:25930710

  2. Foundations

    NASA Astrophysics Data System (ADS)

    Harteveld, Casper

    A building will more likely collapse if it does not have any proper foundations. Similarly, the design philosophy of Triadic Game Design (TGD) needs to reside on solid building blocks, otherwise the concept will collapse as well. In this level I will elaborate on these building blocks. First I will explain what the general idea of TGD is. It is a design philosophy, for sure, but one which stresses that an “optimum” needs to be found in a design space constituted by three different worlds: Reality, Meaning, and Play. Additionally, these worlds need to be considered simultaneously and be treated equally. The latter requires balancing the worlds which may result in different tensions, within and between two or three of the worlds. I continue by discussing each of the worlds and showing their perspective on the field of games with a meaningful purpose. From this, we clearly see that it is feasible to think of each world and that the idea makes sense. I substantiate this further by relating the notion of player and similar approaches to this framework. This level is quite a tough pill to swallow yet essential for finishing the other levels. Do not cheat or simply skip this level, but just take a big cup of coffee or tea and start reading it.

  3. AChE inhibition: one dominant factor for swimming behavior changes of Daphnia magna under DDVP exposure.

    PubMed

    Ren, Zongming; Zhang, Xu; Wang, Xiaoguang; Qi, Pingping; Zhang, Biao; Zeng, Yang; Fu, Rongshu; Miao, Mingsheng

    2015-02-01

    As a key enzyme that hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses of both vertebrates and invertebrates, acetylcholinesterase (AChE) is strongly inhibited by organophosphates. AChE inhibition may induce the decrease of swimming ability. According to previous research, swimming behavior of different aquatic organisms could be affected by different chemicals, and there is a shortage of research on direct correlation analysis between swimming behavior and biochemical indicators. Therefore, swimming behavior and whole-body AChE activity of Daphnia magna under dichlorvos (DDVP) exposure were identified in order to clarify the relationship between behavioral responses and AChE inhibition in this study. In the beginning, AChE activity was similar in all treatments with the control. During all exposures, the tendency of AChE activity inhibition was the same as the behavioral responses of D. magna. The AChE activity of individuals without movement would decrease to about zero in several minutes. The correlation analysis between swimming behavior of D. magna and AChE activity showed that the stepwise behavioral response was mainly decided by AChE activity. All of these results suggested that the toxicity characteristics of DDVP as an inhibitor of AChE on the swimming behavior of organisms were the same, and the AChE activity inhibition could induce loss of the nerve conduction ability, causing hyperactivity, loss of coordination, convulsions, paralysis and other kinds of behavioral changes, which was illustrated by the stepwise behavioral responses under different environmental stresses.

  4. Effect of pharmaceuticals exposure on acetylcholinesterase (AchE) activity and on the expression of AchE gene in the monogonont rotifer, Brachionus koreanus.

    PubMed

    Rhee, Jae-Sung; Kim, Bo-Mi; Jeong, Chang-Bum; Park, Heum Gi; Leung, Kenneth Mei Yee; Lee, Young-Mi; Lee, Jae-Seong

    2013-11-01

    Pharmaceuticals are widely used in human and veterinary medicine. However, they are emerging as a significant contaminant in aquatic environments through wastewater. Due to the persistent and accumulated properties of pharmaceuticals via the food web, their potential harmful effects on aquatic animals are a great concern. In this study, we investigated the effects of six pharmaceuticals: acetaminophen, ATP; atenolol, ATN; carbamazepine, CBZ; oxytetracycline, OTC; sulfamethoxazole, SMX; and trimethoprim, TMP on acetylcholinesterase (AChE; EC 3.1.1.7) activity and its transcript expression with chlorpyrifos (as a positive control) in the monogonont rotifer, Brachionus koreanus. ATP, CBZ, and TMP exposure also remarkably inhibited Bk-AChE activity at 100 μg/L (24 h) and 1000 μg/L (12 h and 24 h). ATP, CBZ, and TMP exposure showed a significant decrease in the Bk-AChE mRNA level in a concentration-dependent manner. However, in the case of OTC and SMX, a slight decrease in Bk-AChE mRNA expression was found but only at the highest concentration. The time-course experiments showed that ATP positively induced Bk-AChE mRNA 12 h after exposure at both 100 and 1000 μg/L, while the Bk-AChE mRNA expression was significantly downregulated over 6 to 24 h after exposure to 1000 μg/L of CBZ, OTC, SMX, and TMP. Our findings suggest that Bk-AChE would be a useful biomarker for risk assessment of pharmaceutical compounds as an early signal of their toxicity in aquatic environments. Particularly, ATP, CBZ, and TMP may have a toxic cholinergic effect on rotifer B. koreanus by inhibiting AChE activity. PMID:24028855

  5. Circannual rhythms of acetylcholinesterase (AChE) activity in the freshwater fish Cnesterodon decemmaculatus.

    PubMed

    Menéndez-Helman, Renata J; Ferreyroa, Gisele V; dos Santos Afonso, Maria; Salibián, Alfredo

    2015-01-01

    The use of biomarkers as a tool to assess responses of organisms exposed to pollutants in toxicity bioassays, as well as in aquatic environmental risk assessment protocols, requires the understanding of the natural fluctuation of the particular biomarker. The aim of this study was to characterize the intrinsic variations of acetylcholinesterase (AChE) activity in tissues of a native freshwater teleost fish to be used as biomarker in toxicity tests, taking into account both seasonal influence and fish size. Specific AChE activity was measured by the method of Ellman et al. (1961) in homogenates of fish anterior section finding a seasonal variability. The highest activity was observed in summer, decreasing significantly below 40% in winter. The annual AChE activity cycle in the anterior section was fitted to a sinusoidal function with a period of 11.2 months. Moreover, an inverse relationship between enzymatic activity and the animal size was established. The results showed that both the fish length and seasonal variability affect AChE activity. AChE activity in fish posterior section showed a similar trend to that in the anterior section, while seasonal variations of the activity in midsection were observed but differences were not statistically significant. In addition, no relationship between AChE and total tissue protein was established in the anterior and posterior sections suggesting that the circannual rhythms observed are AChE-specific responses. Results highlight the importance of considering both the fish size and season variations to reach valid conclusions when AChE activity is employed as neurotoxicity biomarker.

  6. Cholinesterases in development: AChE as a firewall to inhibit cell proliferation and support differentiation.

    PubMed

    Layer, Paul G; Klaczinski, Janine; Salfelder, Anika; Sperling, Laura E; Thangaraj, Gopenath; Tuschl, Corina; Vogel-Höpker, Astrid

    2013-03-25

    Acetylcholinesterase (AChE) is a most remarkable protein, not only because it is one of the fastest enzymes in nature, but also since it appears in many molecular forms and is regulated by elaborate genetic networks. AChE is expressed in many tissues during development and in mature organisms, as well as in healthy and diseased states. In search for alternative, "non-classical" functions of cholinesterases (ChEs), AChE could either work within the frame of classic cholinergic systems, but in non-neural tissues ("non-synaptic function"), or act non-enzymatically. Here, we review briefly some of the major ideas and advances of this field, and report on some recent progress from our own experimental work, e.g. that (i) non-neural ChEs have pronounced, predominantly enzymatic effects on early embryonic (limb) development in chick and mouse, that (ii) retinal R28 cells of the rat overexpressing synaptic AChE present a significantly decreased cell proliferation, and that (iii) in developing chick retina ACh-synthesizing and ACh-degrading cells originate from the same postmitotic precursor cells, which later form two locally opposing cell populations. We suggest that such distinct distributions of ChAT(+) vs. AChE(+) cells in the inner half retina provide graded distributions of ACh, which can direct cell differentiation and network formation. Thus, as corroborated by works from many labs, AChE can be considered a highly co-opting protein, which can combine enzymatic and non-enzymatic functions within one molecule. PMID:23047026

  7. Natural AChE Inhibitors from Plants and their Contribution to Alzheimer’s Disease Therapy

    PubMed Central

    Murray, Ana Paula; Faraoni, María Belén; Castro, María Julia; Alza, Natalia Paola; Cavallaro, Valeria

    2013-01-01

    As acetylcholinesterase (AChE) inhibitors are an important therapeutic strategy in Alzheimer’s disease, efforts are being made in search of new molecules with anti-AChE activity. The fact that naturally-occurring compounds from plants are considered to be a potential source of new inhibitors has led to the discovery of an important number of secondary metabolites and plant extracts with the ability of inhibiting the enzyme AChE, which, according to the cholinergic hypothesis, increases the levels of the neurotransmitter acetylcholine in the brain, thus improving cholinergic functions in patients with Alzheimer’s disease and alleviating the symptoms of this neurological disorder. This review summarizes a total of 128 studies which correspond to the most relevant research work published during 2006-2012 (1st semester) on plant-derived compounds, plant extracts and essential oils found to elicit AChE inhibition. PMID:24381530

  8. Nanoparticles Ease Aching Joints in Mice

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_161188.html Nanoparticles Ease Aching Joints in Mice Treatment might one ... News) -- New research in mice suggests that tiny nanoparticles might one day be a better way to ...

  9. Analysis of AchE and LDH in mollusc, Lamellidens marginalis after exposure to chlorpyrifos.

    PubMed

    Amanullah, B; Stalin, A; Prabu, P; Dhanapal, S

    2010-07-01

    The enzymes Acetylcholinesterase (AchE) and Lactatedehydrogenase (LDH) are used as biological markers in the present study. Enzymes are highly sensitive and used to evaluate the biological effects of organophosphate pesticide chlorpyrifos in freshwater mussel Lamellidens marginalis. The test organisms were exposed to sub-lethal concentration (5 ppm) of chlorpyrifos for 30 days and allowed to recover for seven days. A distinct reduction of the enzyme AchE (34 +/- 3.3 U l(-1)) was found in the treated hepatopancreas. A significant increase in LDH activity in gill, hepatopancreas and muscle was observed. There was a significant recovery in AchE and LDH in the different tissues, after seven days recovery period.. Hence, the changes in the enzymes are found as the best biomarkering tool to evaluate the effect of organophosphate pesticide chlorpyrifos on the aquatic biota.

  10. AChE biosensor based on zinc oxide sol-gel for the detection of pesticides.

    PubMed

    Sinha, Ravi; Ganesana, Mallikarjunarao; Andreescu, Silvana; Stanciu, Lia

    2010-02-28

    Zinc oxide has been used as a matrix for immobilization of acetylcholinesterase (AChE) and detection of the pesticide paraoxon. The immobilized enzyme retained its enzymatic activity up to three months when stored in phosphate buffered saline (pH 7.4) at 4 degrees C. An amperometric biosensor for the detection of paraoxon was designed. The biosensor detected paraoxon in the range 0.035-1.38 ppm and can be used to detect other AChE inhibiting organophosphate pesticides. PMID:20113735

  11. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease.

    PubMed

    Tommonaro, Giuseppina; García-Font, Nuria; Vitale, Rosa Maria; Pejin, Boris; Iodice, Carmine; Cañadas, Sixta; Marco-Contelles, José; Oset-Gasque, María Jesús

    2016-10-21

    Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 ± 0.24 μM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of

  12. Avarol derivatives as competitive AChE inhibitors, non hepatotoxic and neuroprotective agents for Alzheimer's disease.

    PubMed

    Tommonaro, Giuseppina; García-Font, Nuria; Vitale, Rosa Maria; Pejin, Boris; Iodice, Carmine; Cañadas, Sixta; Marco-Contelles, José; Oset-Gasque, María Jesús

    2016-10-21

    Avarol is a marine sesquiterpenoid hydroquinone, previously isolated from the marine sponge Dysidea avara Schmidt (Dictyoceratida), with antiinflammatory, antitumor, antioxidant, antiplatelet, anti-HIV, and antipsoriatic effects. Recent findings indicate that some thio-avarol derivatives exhibit acetylcholinesterase (AChE) inhibitory activity. The multiple pharmacological properties of avarol, thio-avarol and/or their derivatives prompted us to continue the in vitro screening, focusing on their AChE inhibitory and neuroprotective effects. Due to the complex nature of Alzheimer's disease (AD), there is a renewed search for new, non hepatotoxic anticholinesterasic compounds. This paper describes the synthesis and in vitro biological evaluation of avarol-3'-thiosalicylate (TAVA) and thiosalycil-prenyl-hydroquinones (TPHs), as non hepatotoxic anticholinesterasic agents, showing a good neuroprotective effect on the decreased viability of SHSY5Y human neuroblastoma cells induced by oligomycin A/rotenone and okadaic acid. A molecular modeling study was also undertaken on the most promising molecules within the series to elucidate their AChE binding modes and in particular the role played by the carboxylate group in enzyme inhibition. Among them, TPH4, bearing a geranylgeraniol substituent, is the most significant Electrophorus electricus AChE (EeAChE) inhibitor (IC50 = 6.77 ± 0.24 μM), also endowed with a moderate serum horse butyrylcholinesterase (eqBuChE) inhibitory activity, being also the least hepatotoxic and the best neuroprotective compound of the series. Thus, TPHs represents a new family of synthetic compounds, chemically related to the natural compound avarol, which has been discovered for the potential treatment of AD. Findings prove the relevance of TPHs as a new possible generation of competitive AChE inhibitors pointing out the importance of the salycilic substituents on the hydroquinone ring. Since these compounds do not belong to the class of

  13. Altered GPI modification of insect AChE improves tolerance to organophosphate insecticides.

    PubMed

    Kakani, Evdoxia G; Bon, Suzanne; Massoulié, Jean; Mathiopoulos, Kostas D

    2011-03-01

    The olive fruit fly Bactrocera oleae is the most destructive and intractable pest of olives. The management of B. oleae has been based on the use of organophosphate (OP) insecticides, a practice that induced resistance. OP-resistance in the olive fly was previously shown to be associated with two mutations in the acetylcholinesterase (AChE) enzyme that, apparently, hinder the entrance of the OP into the active site. The search for additional mutations in the ace gene that encodes AChE revealed a short deletion of three glutamines (Δ3Q) from a stretch of five glutamines, in the C-terminal peptide that is normally cleaved and substituted by a GPI anchor. We verified that AChEs from B. oleae and other Dipterans are actually GPI-anchored, although this is not predicted by the "big-PI" algorithm. The Δ3Q mutation shortens the unusually long hydrophilic spacer that follows the predicted GPI attachment site and may thus improve the efficiency of GPI anchor addition. We expressed the wild type B. oleae AChE, the natural mutant Δ3Q and a constructed mutant lacking all 5 consecutive glutamines (Δ5Q) in COS cells and compared their kinetic properties. All constructs presented identical K(m) and k(cat) values, in agreement with the fact that the mutations did not affect the catalytic domain of the enzyme. In contrast, the mutants produced higher AChE activity, suggesting that a higher proportion of the precursor protein becomes GPI-anchored. An increase in the number of GPI-anchored molecules in the synaptic cleft may reduce the sensitivity to insecticides.

  14. A selective molecularly imprinted polymer for immobilization of acetylcholinesterase (AChE): an active enzyme targeted and efficient method.

    PubMed

    Demirci, Gökhan; Doğaç, Yasemin İspirli; Teke, Mustafa

    2015-11-01

    In the present study, we immobilized acetylcholinesterase (AChE) enzyme onto acetylcholine removed imprinted polymer and acetylcholine containing polymer. First, the polymers were produced with acetylcholine, substrate of AChE, by dispersion polymerization. Then, the enzyme was immobilized onto the polymers by using two different methods: In the first method (method A), acetylcholine was removed from the polymer, and then AChE was immobilized onto this polymer (acetylcholine removed imprinted polymer). In the second method (method B), AChE was immobilized onto acetylcholine containing polymer by affinity. In method A, enzyme-specific species (binding sites) occurred by removing acetylcholine from the polymer. The immobilized AChE reached 240% relative specific activity comparison with free AChE because the active enzyme molecules bounded onto the polymer. Transmission electron microscopy results were taken before and after immobilization of AChE for the assessment of morphological structure of polymer. Also, the experiments, which include optimum temperature (25-65 °C), optimum pH (3-10), thermal stability (4-70 °C), kinetic parameters, operational stability and reusability, were performed to determine the characteristic of the immobilized AChE.

  15. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver.

    PubMed

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  16. An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch.

    PubMed

    Zhao, Hengqiang; Zhou, Siduo; Zhang, Minmin; Feng, Jinhong; Wang, Shanshan; Wang, Daijie; Geng, Yanling; Wang, Xiao

    2016-02-20

    In this study, an in vitro acetylcholinesterase (AChE) inhibition assay based on microplate reader combined with ultrafiltration high performance liquid chromatography-electrospray quadrupole time of flight mass (UF-HPLC-ESI-Q-TOF/MS) was developed for the rapid screening and identification of acetylcholinesterase inhibitors (AChEI) from roots of Coptis chinensis Franch. Incubation conditions such as enzyme concentration, incubation time, incubation temperature and co-solvent was optimized so as to get better screening results. Five alkaloids including columbamine, jatrorrhizine, coptisine, palmatine and berberine were found with AChE inhibition activity in the 80% ethanol extract of C. chinensis Franch. The screened compounds were identified by HPLC-DAD-ESI-Q-TOF/MS compared with the reference stands and literatures. The screened results were verified by in vitro AChE inhibition assays, palmatine showed the best AChE inhibitory activities with IC50 values of 36.6μM among the five compounds. Results of the present study indicated that the combinative method using in vitro AChE inhibition assay and UF-HPLC-ESI-Q-TOF/MS could be widely applied for rapid screening and identification of AChEI from complex TCM extract.

  17. Epilepsy Foundation

    MedlinePlus

    ... Gastaut Syndrome Infantile Spasms and Tuberous Sclerosis Complex Facebook < > Epilepsy Foundation of America Watch the next George ... consider the Epilepsy Foundation your #UnwaveringAlly on Twitter, Facebook, and Instagram! Epilepsy Foundation of America Star Trek ...

  18. Acetylcholinesterase (AChE) gene modification in transgenic animals: functional consequences of selected exon and regulatory region deletion.

    PubMed

    Camp, Shelley; Zhang, Limin; Marquez, Michael; de la Torre, Brian; Long, Jeffery M; Bucht, Goran; Taylor, Palmer

    2005-12-15

    AChE is an alternatively spliced gene. Exons 2, 3 and 4 are invariantly spliced, and this sequence is responsible for catalytic function. The 3' alternatively spliced exons, 5 and 6, are responsible for AChE disposition in tissue [J. Massoulie, The origin of the molecular diversity and functional anchoring of cholinesterases. Neurosignals 11 (3) (2002) 130-143; Y. Li, S. Camp, P. Taylor, Tissue-specific expression and alternative mRNA processing of the mammalian acetylcholinesterase gene. J. Biol. Chem. 268 (8) (1993) 5790-5797]. The splice to exon 5 produces the GPI anchored form of AChE found in the hematopoietic system, whereas the splice to exon 6 produces a sequence that binds to the structural subunits PRiMA and ColQ, producing AChE expression in brain and muscle. A third alternative RNA species is present that is not spliced at the 3' end; the intron 3' of exon 4 is used as coding sequence and produces the read-through, unanchored form of AChE. In order to further understand the role of alternative splicing in the expression of the AChE gene, we have used homologous recombination in stem cells to produce gene specific deletions in mice. Alternatively and together exon 5 and exon 6 were deleted. A cassette containing the neomycin gene flanked by loxP sites was used to replace the exon(s) of interest. Tissue analysis of mice with exon 5 deleted and the neomycin cassette retained showed very low levels of AChE expression, far less than would have been anticipated. Only the read-through species of the enzyme was produced; clearly the inclusion of the selection cassette disrupted splicing of exon 4 to exon 6. The selection cassette was then deleted in exon 5, exon 6 and exons 5 + 6 deleted mice by breeding to Ella-cre transgenic mice. AChE expression in serum, brain and muscle has been analyzed. Another AChE gene targeted mouse strain involving a region in the first intron, found to be critical for AChE expression in muscle cells [S. Camp, L. Zhang, M. Marquez, B

  19. N Ach at Home and Abroad

    ERIC Educational Resources Information Center

    Allen, Vernon L.

    1971-01-01

    A review of Achievement-Related Motives in Children (Russell Sage Foundation, 1969) Charles P. Smith, Editor, and The Achievement Motive in High School Boys (National Council of Educational Research and Training, 1969) by Prayag Mehto. (CK)

  20. Residues Responsible for the Selectivity of α-Conotoxins for Ac-AChBP or nAChRs

    PubMed Central

    Lin, Bo; Xiang, Shihua; Li, Mengsen

    2016-01-01

    Nicotinic acetylcholine receptors (nAChRs) are targets for developing new drugs to treat severe pain, nicotine addiction, Alzheimer disease, epilepsy, etc. α-Conotoxins are biologically and chemically diverse. With 12–19 residues and two disulfides, they can be specifically selected for different nAChRs. Acetylcholine-binding proteins from Aplysia californica (Ac-AChBP) are homologous to the ligand-binding domains of nAChRs and pharmacologically similar. X-ray structures of the α-conotoxin in complex with Ac-AChBP in addition to computer modeling have helped to determine the binding site of the important residues of α-conotoxin and its affinity for nAChR subtypes. Here, we present the various α-conotoxin residues that are selective for Ac-AChBP or nAChRs by comparing the structures of α-conotoxins in complex with Ac-AChBP and by modeling α-conotoxins in complex with nAChRs. The knowledge of these binding sites will assist in the discovery and design of more potent and selective α-conotoxins as drug leads. PMID:27727162

  1. Anisotropic a-C:H from Compression of Polyacetylene

    NASA Astrophysics Data System (ADS)

    Bernasconi, M.; Parrinello, M.; Chiarotti, G. L.; Focher, P.; Tosatti, E.

    1996-03-01

    We have simulated the transformation of crystalline trans-polyacetylene into a-C:H under pressure by constant pressure ab initio molecular dynamics. Polyacetylene undergoes a gradual saturation of C-C bonds via chain interlinks, ending up at ~50 GPa with a-C:H containing 80% sp3 carbon atoms. The sp2-->sp3 conversion is irreversible and does not reverse by returning to zero pressure. The final a-C:H is a wide gap insulator and, at variance with the conventionally generated a-C:H, is highly anisotropic keeping some memory of the original polyacetylene chain axis.

  2. Modelling interactions between Loop1 of Fasciculin2 (Fas2) and Torpedo californica acetylcholinesterase ( Tc AChE)

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Gu, Jiande; Leszczynski, Jerzy

    2006-11-01

    Four interaction models for the binding of Torpedo californica acetylcholinesterase ( TcAChE) with Loop1 of Fasciculin2 are investigated at the B3LYP/6-311G(d,p) level of theory. The total binding energy of three fragments (P1-P3) which belong to the omega loop Cys67-Cys94 of TcAChE contributes almost 67% of the entire binding, suggesting the domination of this omega loop on the interaction between AChE and Loop1 of Fas2. The energy decomposition illustrates that the interactions mainly consist of electrostatic components. The polar solvent which reduces the binding energies of the studied models implies the significant impact of the solvent on the binding of Fas2 and AChE.

  3. Neurophysiological predictors of long term response to AChE inhibitors in AD patients

    PubMed Central

    Di, L; Oliviero, A; Pilato, F; Saturno, E; Dileone, M; Marra, C; Ghirlanda, S; Ranieri, F; Gainotti, G; Tonali, P

    2005-01-01

    Background: In vivo evaluation of cholinergic circuits of the human brain has recently been introduced using a transcranial magnetic stimulation (TMS) protocol based on coupling peripheral nerve stimulation with motor cortex TMS (short latency afferent inhibition, SAI). SAI is reduced in Alzheimer's disease (AD) and drugs enhancing cholinergic transmission increase SAI. Methods: We evaluated whether SAI testing, together with SAI test-retest, after a single dose of the acetylcholinesterase (AChE) inhibitor rivastigmine, might be useful in predicting the response after 1 year treatment with rivastigmine in 16 AD patients. Results: Fourteen AD patients had pathologically reduced SAI. SAI was increased after administration of a single oral dose of rivastigmine in AD patients with abnormal baseline SAI, but individual responses to rivastigmine varied widely, with SAI change ranging from an increase in inhibition of ∼50% of test size to no change. Baseline SAI and the increase in SAI after a single dose of rivastigmine were correlated with response to long term treatment. A normal SAI in baseline conditions, or an abnormal SAI in baseline conditions that was not greatly increased by a single oral dose of rivastigmine, were invariably associated with poor response to long term treatment, while an abnormal SAI in baseline conditions in conjunction with a large increase in SAI after a single dose of rivastigmine was associated with good response to long term treatment in most of the patients. Conclusions: Evaluation of SAI may be useful for identifying AD patients likely to respond to treatment with AChE inhibitors. PMID:16024879

  4. ABIM Foundation

    MedlinePlus

    ... ON TWITTER ABIM Foundation ABIM Foundation is using Facebook to share helpful information. We welcome comments, ideas, ... the conventions of civil discourse and comply with Facebook Terms of Use. While we encourage fans to ...

  5. Dysautonomia Foundation

    MedlinePlus

    ... More about FD .) Research funded by the Dysautonomia Foundation has led to a number of breakthroughs in ... our FD screening awareness video here .) The Dysautonomia Foundation is a 501c3 nonprofit organization that has established ...

  6. Marfan Foundation

    MedlinePlus

    ... Foundation Brings its 32nd Annual Conference to Rochester, MN, August 4-7, 2016 The Marfan Foundation will hold its 32nd Annual Conference in Rochester, MN, on August 4-7. The conference, organized in ...

  7. Gripped by Gout: Avoiding the Ache and Agony

    MedlinePlus

    ... please review our exit disclaimer . Subscribe Gripped by Gout Avoiding the Ache and Agony Sudden, painful swelling ... toe is often the first warning sign of gout. It can affect other joints as well. Without ...

  8. Acetylcholinesterase (AChE) is an important link in the apoptotic pathway induced by hyperglycemia in Y79 retinoblastoma cell line

    PubMed Central

    Masha'our, R. Shehadeh; Heinrich, R.; Garzozi, H. J.; Perlman, I.

    2012-01-01

    Acetylcholinesterase (AChE) expression was found to be induced in the mammalian CNS, including the retina, by different types of stress leading to cellular apoptosis. Here, we tested possible involvement of AChE in hyperglycemia-induced apoptosis in a retinal cell line. Y79 retinoblastoma cells were incubated in starvation media (1% FBS and 1 mg/ml glucose) for 16–24 h, and then exposed to hyperglycemic environment by raising extracellular glucose concentrations to a final level of 3.5 mg/ml or 6 mg/ml. Similar levels of mannitol were used as control for hyperosmolarity. Cells were harvested at different time intervals for analysis of apoptosis and AChE protein expression. Apoptosis was detected by the cleavage of Poly ADP-ribose polymerase (PARP) using western blot, and by Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end-labeling (TUNEL) assay. AChE protein expression and activity was detected by western blot and by the Karnovsky and Roots method, respectively. MissionTM shRNA for AChE was used to inhibit AChE protein expression. Treating Y79 cells with 3.5 mg/ml of glucose, but not with 3.5 mg/ml mannitol, induced apoptosis which was confirmed by TUNEL assay and by cleavage of PARP. A part of the signaling pathway accompanying the apoptotic process involved up-regulation of the AChE-R variant and an N-extended AChE variant as verified at the mRNA and protein level. Inhibition of AChE protein expression by shRNA protected Y79 cell from entering the apoptotic pathway. Our data suggest that expression of an N-extended AChE variant, most probably an R isoform, is involved in the apoptotic pathway caused by hyperglycemia in Y79 cells. PMID:22685426

  9. Acetylcholinesterase (AChE) is an important link in the apoptotic pathway induced by hyperglycemia in Y79 retinoblastoma cell line.

    PubMed

    Masha'our, R Shehadeh; Heinrich, R; Garzozi, H J; Perlman, I

    2012-01-01

    Acetylcholinesterase (AChE) expression was found to be induced in the mammalian CNS, including the retina, by different types of stress leading to cellular apoptosis. Here, we tested possible involvement of AChE in hyperglycemia-induced apoptosis in a retinal cell line. Y79 retinoblastoma cells were incubated in starvation media (1% FBS and 1 mg/ml glucose) for 16-24 h, and then exposed to hyperglycemic environment by raising extracellular glucose concentrations to a final level of 3.5 mg/ml or 6 mg/ml. Similar levels of mannitol were used as control for hyperosmolarity. Cells were harvested at different time intervals for analysis of apoptosis and AChE protein expression. Apoptosis was detected by the cleavage of Poly ADP-ribose polymerase (PARP) using western blot, and by Terminal deoxynucleotidyl-transferase-mediated dUTP nick-end-labeling (TUNEL) assay. AChE protein expression and activity was detected by western blot and by the Karnovsky and Roots method, respectively. Mission(TM) shRNA for AChE was used to inhibit AChE protein expression. Treating Y79 cells with 3.5 mg/ml of glucose, but not with 3.5 mg/ml mannitol, induced apoptosis which was confirmed by TUNEL assay and by cleavage of PARP. A part of the signaling pathway accompanying the apoptotic process involved up-regulation of the AChE-R variant and an N-extended AChE variant as verified at the mRNA and protein level. Inhibition of AChE protein expression by shRNA protected Y79 cell from entering the apoptotic pathway. Our data suggest that expression of an N-extended AChE variant, most probably an R isoform, is involved in the apoptotic pathway caused by hyperglycemia in Y79 cells. PMID:22685426

  10. Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

    PubMed

    Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

    2015-10-01

    Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

  11. Intensified vmPFC surveillance over PTSS under perturbed microRNA-608/AChE interaction

    PubMed Central

    Lin, T; Simchovitz, A; Shenhar-Tsarfaty, S; Vaisvaser, S; Admon, R; Hanin, G; Hanan, M; Kliper, E; Bar-Haim, Y; Shomron, N; Fernandez, G; Lubin, G; Fruchter, E; Hendler, T; Soreq, H

    2016-01-01

    Trauma causes variable risk of posttraumatic stress symptoms (PTSS) owing to yet-unknown genome–neuronal interactions. Here, we report co-intensified amygdala and ventromedial prefrontal cortex (vmPFC) emotional responses that may overcome PTSS in individuals with the single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene. We have recently shown that in individuals with the minor rs17228616 allele, this SNP interrupts AChE suppression by microRNA (miRNA)-608, leading to cortical elevation of brain AChE and reduced cortisol and the miRNA-608 target GABAergic modulator CDC42, all stress-associated. To examine whether this SNP has effects on PTSS and threat-related brain circuits, we exposed 76 healthy Israel Defense Forces soldiers who experienced chronic military stress to a functional magnetic resonance imaging task of emotional and neutral visual stimuli. Minor allele individuals predictably reacted to emotional stimuli by hyperactivated amygdala, a hallmark of PTSS and a predisposing factor of posttraumatic stress disorder (PTSD). Despite this, minor allele individuals showed no difference in PTSS levels. Mediation analyses indicated that the potentiated amygdala reactivity in minor allele soldiers promoted enhanced vmPFC recruitment that was associated with their limited PTSS. Furthermore, we found interrelated expression levels of several miRNA-608 targets including CD44, CDC42 and interleukin 6 in human amygdala samples (N=7). Our findings suggest that miRNA-608/AChE interaction is involved in the threat circuitry and PTSS and support a model where greater vmPFC regulatory activity compensates for amygdala hyperactivation in minor allele individuals to neutralize their PTSS susceptibility. PMID:27138800

  12. An acetylcholinesterase (AChE) biosensor with enhanced solvent resistance based on chitosan for the detection of pesticides.

    PubMed

    Warner, John; Andreescu, Silvana

    2016-01-01

    Solvent tolerance of immobilized enzymes is important for many biosensing and biotechnological applications. In this paper we report an acetylcholinesterase (AChE) biosensor based on chitosan that exhibits high solvent resistance and enables sensitive detection of pesticides in presence of a high content of organic solvents. The solvent effect was established comparatively for the enzyme immobilized in chitosan and covalently cross-linked with glutaraldehyde. The activity of the immobilized AChE was dependent on the immobilization method and solvent type. The enzyme entrapped in chitosan fully conserved its activity in up to 25% methanol, 15% acetonitrile and 100% cyclohexane while the enzyme cross-linked with glutaraldehyde gradually lost its activity starting at 5% acetonitrile and methanol, and showed variable levels in cyclohexane. The detection limits of the biosensor for paraoxon were: 7.5 nM in 25% methanol, 100 nM in 15% acetonitrile and 2.5 μM in 100% cyclohexane. This study demonstrates that chitosan provides an excellent immobilization environment for AChE biosensors designed to operate in environments containing high amounts of organic solvents. It also highlights the effect of the immobilization material and solvent type on enzyme stability. These findings can enable future selection of the immobilization matrix and solvent type for the development of organic phase enzyme based systems.

  13. An acetylcholinesterase (AChE) biosensor with enhanced solvent resistance based on chitosan for the detection of pesticides.

    PubMed

    Warner, John; Andreescu, Silvana

    2016-01-01

    Solvent tolerance of immobilized enzymes is important for many biosensing and biotechnological applications. In this paper we report an acetylcholinesterase (AChE) biosensor based on chitosan that exhibits high solvent resistance and enables sensitive detection of pesticides in presence of a high content of organic solvents. The solvent effect was established comparatively for the enzyme immobilized in chitosan and covalently cross-linked with glutaraldehyde. The activity of the immobilized AChE was dependent on the immobilization method and solvent type. The enzyme entrapped in chitosan fully conserved its activity in up to 25% methanol, 15% acetonitrile and 100% cyclohexane while the enzyme cross-linked with glutaraldehyde gradually lost its activity starting at 5% acetonitrile and methanol, and showed variable levels in cyclohexane. The detection limits of the biosensor for paraoxon were: 7.5 nM in 25% methanol, 100 nM in 15% acetonitrile and 2.5 μM in 100% cyclohexane. This study demonstrates that chitosan provides an excellent immobilization environment for AChE biosensors designed to operate in environments containing high amounts of organic solvents. It also highlights the effect of the immobilization material and solvent type on enzyme stability. These findings can enable future selection of the immobilization matrix and solvent type for the development of organic phase enzyme based systems. PMID:26695264

  14. Selenofuranoside Ameliorates Memory Loss in Alzheimer-Like Sporadic Dementia: AChE Activity, Oxidative Stress, and Inflammation Involvement.

    PubMed

    Chiapinotto Spiazzi, Cristiano; Bucco Soares, Melina; Pinto Izaguirry, Aryele; Musacchio Vargas, Laura; Zanchi, Mariane Magalhães; Frasson Pavin, Natasha; Ferreira Affeldt, Ricardo; Seibert Lüdtke, Diogo; Prigol, Marina; Santos, Francielli Weber

    2015-01-01

    Alzheimer's disease (AD) is becoming more common due to the increase in life expectancy. This study evaluated the effect of selenofuranoside (Se) in an Alzheimer-like sporadic dementia animal model. Male mice were divided into 4 groups: control, Aβ, Se, and Aβ + Se. Single administration of Aβ peptide (fragments 25-35; 3 nmol/3 μL) or distilled water was administered via intracerebroventricular (i.c.v.) injection. Selenofuranoside (5 mg/kg) or vehicle (canola oil) was administered orally 30 min before Aβ and for 7 subsequent days. Memory was tested through the Morris water maze (MWM) and step-down passive-avoidance (SDPA) tests. Antioxidant defenses along with reactive species (RS) were assessed. Inflammatory cytokines levels and AChE activity were measured. SOD activity was inhibited in the Aβ group whereas RS were increased. AChE activity, GSH, and IL-6 levels were increased in the Aβ group. These changes were reflected in impaired cognition and memory loss, observed in both behavioral tests. Se compound was able to protect against memory loss in mice in both behavioral tests. SOD and AChE activities as well as RS and IL-6 levels were also protected by Se administration. Therefore, Se is promising for further studies.

  15. Screening of POP pollution by AChE and EROD activities in Zebra mussels from the Italian Great Lakes.

    PubMed

    Binelli, A; Ricciardi, Francesco; Riva, Consuelo; Provini, Alfredo

    2005-12-01

    The increase of ethoxyresorufin dealkylation (EROD) and the inhibition of acetylcholinesterase (AChE) as biomarkers have been commonly used in vertebrates for the persistent organic pollutants (POPs) biomonitoring of aquatic environments, but very few studies have been performed for invertebrates. Previous researches demonstrated the interference due to some chemicals on EROD and AChE activities of the freshwater bivalve Zebra mussel (Dreissena polymorpha) in laboratory and field studies, showing its possible use for the screening of POP effects. We investigated the contamination of the Italian sub-alpine great lakes (Maggiore, Lugano, Como, Iseo, Garda) by the biomarker approach on Zebra mussel specimens collected at 17 sampling sites with different morphometric characteristics and anthropization levels. Results showed a homogeneous contamination of AChE inhibitors in Lake Garda, Maggiore, Como and Iseo with values ranging from 0.5 to 3 nmol/min/mg proteins and with an average inhibition of about 66% to controls. The planar compounds pollution, able to activate the EROD activity, seems higher in some sampling stations of Lake Garda, Como and Iseo (2-4 pmol/min/mg proteins) than that measured in Lake Lugano (1.5-3 pmol/min/mg proteins). On the contrary, the enzyme activity in Lake Maggiore showed an interesting opposite effect of AhR-binding compounds and trace metals. Finally, the possible use of Zebra mussel specimens maintained at laboratory conditions as controls against the selection of the less polluted sampling site is discussed.

  16. Toxicological and Biochemical Characterizations of AChE in Phosalone-Susceptible and Resistant Populations of the Common Pistachio Psyllid, Agonoscena pistaciae

    PubMed Central

    Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad

    2014-01-01

    The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity (KM) and hydrolyzing efficiency (Vmax) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively

  17. Toxicological and biochemical characterizations of AChE in phosalone-susceptible and resistant populations of the common pistachio psyllid, Agonoscena pistaciae.

    PubMed

    Alizadeh, Ali; Talebi-Jahromi, Khalil; Hosseininaveh, Vahid; Ghadamyari, Mohammad

    2014-01-01

    The toxicological and biochemical characteristics of acetylcholinesterases (AChE) in nine populations of the common pistachio psyllid, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae), were investigated in Kerman Province, Iran. Nine A. pistaciae populations were collected from pistachio orchards, Pistacia vera L. (Sapindales: Anacardiaceae), located in Rafsanjan, Anar, Bam, Kerman, Shahrbabak, Herat, Sirjan, Pariz, and Paghaleh regions of Kerman province. The previous bioassay results showed these populations were susceptible or resistant to phosalone, and the Rafsanjan population was most resistant, with a resistance ratio of 11.3. The specific activity of AChE in the Rafsanjan population was significantly higher than in the susceptible population (Bam). The affinity (K(M)) and hydrolyzing efficiency (Vmax) of AChE on acetylthiocholine iodide, butyrylthiocholine iodide, and propionylthiocholine odide as artificial substrates were clearly lower in the Bam population than that in the Rafsanjan population. These results indicated that the AChE of the Rafsanjan population had lower affinity to these substrates than that of the susceptible population. The higher Vmax value in the Rafsanjan population compared to the susceptible population suggests a possible over expression of AChE in the Rafsanjan population. The in vitro inhibitory effect of several organophosphates and carbamates on AChE of the Rafsanjan and Bam populations was determined. Based on I50, the results showed that the ratios of AChE insensitivity of the resistant to susceptible populations were 23 and 21.7-fold to monocrotophos and phosphamidon, respectively. Whereas, the insensitivity ratios for Rafsanjan population were 0.86, 0.8, 0.78, 0.46, and 0.43 for carbaryl, eserine, propoxur, m-tolyl methyl carbamate, and carbofuran, respectively, suggesting negatively correlated sensitivity to organophosphate-insensitive AChE. Therefore, AChE from the Rafsanjan population showed negatively

  18. Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

    PubMed

    López-Granero, Caridad; Cardona, Diana; Giménez, Estela; Lozano, Rafael; Barril, José; Aschner, Michael; Sánchez-Santed, Fernando; Cañadas, Fernando

    2014-01-01

    Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15 mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme.

  19. Muscarinic ACh Receptors Contribute to Aversive Olfactory Learning in Drosophila

    PubMed Central

    Silva, Bryon; Molina-Fernández, Claudia; Ugalde, María Beatriz; Tognarelli, Eduardo I.; Angel, Cristian; Campusano, Jorge M.

    2015-01-01

    The most studied form of associative learning in Drosophila consists in pairing an odorant, the conditioned stimulus (CS), with an unconditioned stimulus (US). The timely arrival of the CS and US information to a specific Drosophila brain association region, the mushroom bodies (MB), can induce new olfactory memories. Thus, the MB is considered a coincidence detector. It has been shown that olfactory information is conveyed to the MB through cholinergic inputs that activate acetylcholine (ACh) receptors, while the US is encoded by biogenic amine (BA) systems. In recent years, we have advanced our understanding on the specific neural BA pathways and receptors involved in olfactory learning and memory. However, little information exists on the contribution of cholinergic receptors to this process. Here we evaluate for the first time the proposition that, as in mammals, muscarinic ACh receptors (mAChRs) contribute to memory formation in Drosophila. Our results show that pharmacological and genetic blockade of mAChRs in MB disrupts olfactory aversive memory in larvae. This effect is not explained by an alteration in the ability of animals to respond to odorants or to execute motor programs. These results show that mAChRs in MB contribute to generating olfactory memories in Drosophila. PMID:26380118

  20. Nicotinic ACh receptors as therapeutic targets in CNS disorders.

    PubMed

    Dineley, Kelly T; Pandya, Anshul A; Yakel, Jerrel L

    2015-02-01

    The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability by acting on the cys-loop cation-conducting ligand-gated nicotinic ACh receptor (nAChR) channels. These receptors are widely distributed throughout the central nervous system (CNS), being expressed on neurons and non-neuronal cells, where they participate in a variety of physiological responses such as anxiety, the central processing of pain, food intake, nicotine seeking behavior, and cognitive functions. In the mammalian brain, nine different subunits have been found thus far, which assemble into pentameric complexes with much subunit diversity; however, the α7 and α4β2 subtypes predominate in the CNS. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders. Here we will briefly discuss the functional makeup and expression of the nAChRs in mammalian brain, and their role as targets in neurodegenerative diseases (in particular Alzheimer's disease, AD), neurodevelopmental disorders (in particular autism and schizophrenia), and neuropathic pain.

  1. AChR-specific immunosuppressive therapy of myasthenia gravis.

    PubMed

    Luo, Jie; Lindstrom, Jon

    2015-10-15

    Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG.

  2. Bactericidal activity of ACH-702 against nondividing and biofilm Staphylococci.

    PubMed

    Podos, Steven D; Thanassi, Jane A; Leggio, Melissa; Pucci, Michael J

    2012-07-01

    Many bacterial infections involve slow or nondividing bacterial growth states and localized high cell densities. Antibiotics with demonstrated bactericidal activity rarely remain bactericidal at therapeutic concentrations under these conditions. The isothiazoloquinolone (ITQ) ACH-702 is a potent, bactericidal compound with activity against many antibiotic-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). We evaluated its bactericidal activity under conditions where bacterial cells were not dividing and/or had slowed their growth. Against S. aureus cultures in stationary phase, ACH-702 showed concentration-dependent bactericidal activity and achieved a 3-log-unit reduction in viable cell counts within 6 h of treatment at ≥ 16× MIC values; in comparison, the bactericidal quinolone moxifloxacin and the additional comparator compounds vancomycin, linezolid, and rifampin at 16× to 32× MICs showed little or no bactericidal activity against stationary-phase cells. ACH-702 at 32× MIC retained bactericidal activity against stationary-phase S. aureus across a range of inoculum densities. ACH-702 did not kill cold-arrested cells yet remained bactericidal against cells arrested by protein synthesis inhibitors, suggesting that its bactericidal activity against nondividing cells requires active metabolism but not de novo protein synthesis. ACH-702 also showed a degree of bactericidal activity at 16× MIC against S. epidermidis biofilm cells that was superior to that of moxifloxacin, rifampin, and vancomycin. The bactericidal activity of ACH-702 against stationary-phase staphylococci and biofilms suggests potential clinical utility in infections containing cells in these physiological states. PMID:22547614

  3. Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms

    PubMed Central

    Spieker, Janine; Ackermann, Anica; Salfelder, Anika; Vogel-Höpker, Astrid; Layer, Paul G.

    2016-01-01

    Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS). Here, we first analyzed the expression of acetylcholinesterase (AChE) by IHC and of choline acetyltransferase (ChAT) by ISH in developing embryonic chicken limbs (stages HH17-37). AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB) and Alizarin red (AR) stainings, respectively. Both acetylcholine (ACh)- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein. PMID:27574787

  4. Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms.

    PubMed

    Spieker, Janine; Ackermann, Anica; Salfelder, Anika; Vogel-Höpker, Astrid; Layer, Paul G

    2016-01-01

    Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS). Here, we first analyzed the expression of acetylcholinesterase (AChE) by IHC and of choline acetyltransferase (ChAT) by ISH in developing embryonic chicken limbs (stages HH17-37). AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB) and Alizarin red (AR) stainings, respectively. Both acetylcholine (ACh)- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein. PMID:27574787

  5. Combined 3D-QSAR, molecular docking, and molecular dynamics study of tacrine derivatives as potential acetylcholinesterase (AChE) inhibitors of Alzheimer's disease.

    PubMed

    Zhou, An; Hu, Jianping; Wang, Lirong; Zhong, Guochen; Pan, Jian; Wu, Zeyu; Hui, Ailing

    2015-10-01

    Acetylcholinesterase (AChE) is one of the key targets of drugs for treating Alzheimer's disease (AD). Tacrine is an approved drug with AChE-inhibitory activity. In this paper, 3D-QSAR, molecular docking, and molecular dynamics were carried out in order to study 60 tacrine derivatives and their AChE-inhibitory activities. 3D-QSAR modeling resulted in an optimal CoMFA model with q(2) = 0.552 and r(2) = 0.983 and an optimal CoMSIA model with q(2) = 0.581 and r(2) = 0.989. These QSAR models also showed that the steric and H-bond fields of these compounds are important influences on their activities. The interactions between these inhibitors and AChE were further explored through molecular docking and molecular dynamics simulation. A few key residues (Tyr70, Trp84, Tyr121, Trp279, and Phe330) at the binding site of AChE were identified. The results of this study improve our understanding of the mechanisms of AChE inhibitors and afford valuable information that should aid the design of novel potential AChE inhibitors. Graphical Abstract Superposition of backbone atoms of the lowest-energy structure obtained from MD simulation (magenta) onto those of the structure of the initial molecular docking model (green).

  6. Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo.

    PubMed

    Chen, Heng-Wen; He, Xuan-Hui; Yuan, Rong; Wei, Ben-Jun; Chen, Zhong; Dong, Jun-Xing; Wang, Jie

    2016-04-01

    Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs. The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity. Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var. latiofolia. The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro. Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze. The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry. The results showed IC50 of compound 4 was 0.161 μM in vitro. Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (P<0.01), while the AchE increased (P<0.01). Compared with the model group, Ach and ChAT in the positive control group, the high-dose group and the medium-dose group increased (P<0.01), while the AchE decreased (P<0.01). Compound 4 can improve the learning and memory abilities of APPswe/PSΔE9 double-transgenic mice, and the mechanism may be related to the regulation of the relative enzyme in the cholinergic system. PMID:26976216

  7. Cardanol-derived AChE inhibitors: Towards the development of dual binding derivatives for Alzheimer's disease.

    PubMed

    Lemes, Laís Flávia Nunes; de Andrade Ramos, Giselle; de Oliveira, Andressa Souza; da Silva, Fernanda Motta R; de Castro Couto, Gina; da Silva Boni, Marina; Guimarães, Marcos Jorge R; Souza, Isis Nem O; Bartolini, Manuela; Andrisano, Vincenza; do Nascimento Nogueira, Patrícia Coelho; Silveira, Edilberto Rocha; Brand, Guilherme D; Soukup, Ondřej; Korábečný, Jan; Romeiro, Nelilma C; Castro, Newton G; Bolognesi, Maria Laura; Romeiro, Luiz Antonio Soares

    2016-01-27

    Cardanol is a phenolic lipid component of cashew nut shell liquid (CNSL), obtained as the byproduct of cashew nut food processing. Being a waste product, it has attracted much attention as a precursor for the production of high-value chemicals, including drugs. On the basis of these findings and in connection with our previous studies on cardanol derivatives as acetylcholinesterase (AChE) inhibitors, we designed a novel series of analogues by including a protonable amino moiety belonging to different systems. Properly addressed docking studies suggested that the proposed structural modifications would allow the new molecules to interact with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, thus being able to act as dual binding inhibitors. To disclose whether the new molecules showed the desired profile, they were first tested for their cholinesterase inhibitory activity towards EeAChE and eqBuChE. Compound 26, bearing an N-ethyl-N-(2-methoxybenzyl)amine moiety, showed the highest inhibitory activity against EeAChE, with a promising IC50 of 6.6 μM, and a similar inhibition profile of the human isoform (IC50 = 5.7 μM). As another positive feature, most of the derivatives did not show appreciable toxicity against HT-29 cells, up to a concentration of 100 μM, which indicates drug-conform behavior. Also, compound 26 is capable of crossing the blood-brain barrier (BBB), as predicted by a PAMPA-BBB assay. Collectively, the data suggest that the approach to obtain potential anti-Alzheimer drugs from CNSL is worth of further pursuit and development. PMID:26735910

  8. Complete Genome Sequence of Agrobacterium tumefaciens Ach5.

    PubMed

    Huang, Ya-Yi; Cho, Shu-Ting; Lo, Wen-Sui; Wang, Yi-Chieh; Lai, Erh-Min; Kuo, Chih-Horng

    2015-01-01

    Agrobacterium tumefaciens is a phytopathogenic bacterium that causes crown gall disease. The strain Ach5 was isolated from yarrow (Achillea ptarmica L.) and is the wild-type progenitor of other derived strains widely used for plant transformation. Here, we report the complete genome sequence of this bacterium. PMID:26044425

  9. The Ache: Genocide Continues in Paraguay. IWGIA Document No. 17.

    ERIC Educational Resources Information Center

    Munzel, Mark

    In 1972, the Paraguayan Roman Catholic Church protested against the massacre of Indians in Paraguay. This was followed by further protests from Paraguayan intellectuals. These protests led to the removal of Jesus de Pereira, one of the executors of the official Ache policy. Thus, the critics were appeased. Since the beginning of 1973, new protests…

  10. Photolabeling a Nicotinic Acetylcholine Receptor (nAChR) with an (α4)3(β2)2 nAChR-Selective Positive Allosteric Modulator.

    PubMed

    Hamouda, Ayman K; Deba, Farah; Wang, Ze-Jun; Cohen, Jonathan B

    2016-05-01

    Positive allosteric modulators (PAMs) of nicotinic acetylcholine (ACh) receptors (nAChRs) have potential clinical applications in the treatment of nicotine dependence and many neuropsychiatric conditions associated with decreased brain cholinergic activity, and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI) has been identified as a PAM selective for neuronal nAChRs containing theα4 subunit. In this report, we compare CMPI interactions with low-sensitivity (α4)3(β2)2 and high-sensitivity (α4)2(β2)3 nAChRs, and with muscle-type nAChRs. In addition, we use the intrinsic reactivity of [(3)H]CMPI upon photolysis at 312 nm to identify its binding sites inTorpedonAChRs. Recording fromXenopusoocytes, we found that CMPI potentiated maximally the responses of (α4)3(β2)2nAChR to 10μM ACh (EC10) by 400% and with anEC50of ∼1µM. CMPI produced a left shift of the ACh concentration-response curve without altering ACh efficacy. In contrast, CMPI inhibited (∼35% at 10µM) ACh responses of (α4)2(β2)3nAChRs and fully inhibited human muscle andTorpedonAChRs with IC50values of ∼0.5µM. Upon irradiation at 312 nm, [(3)H]CMPI photoincorporated into eachTorpedo[(α1)2β1γδ] nAChR subunit. Sequencing of peptide fragments isolated from [(3)H]CMPI-photolabeled nAChR subunits established photolabeling of amino acids contributing to the ACh binding sites (αTyr(190),αTyr(198),γTrp(55),γTyr(111),γTyr(117),δTrp(57)) that was fully inhibitable by agonist and lower-efficiency, state-dependent [(3)H]CMPI photolabeling within the ion channel. Our results establish that CMPI is a potent potentiator of nAChRs containing anα4:α4 subunit interface, and that its intrinsic photoreactivy makes it of potential use to identify its binding sites in the (α4)3(β2)2nAChR. PMID:26976945

  11. Functional Analysis and Molecular Docking studies of Medicinal Compounds for AChE and BChE in Alzheimer’s Disease and Type 2 Diabetes Mellitus

    PubMed Central

    Kaladhar, Dowluru SVGK; Yarla, Nagendra Sastry; Anusha, N.

    2013-01-01

    Acetylcholinesterase and Butyrylcholinesterase share unravelling link with components of metabolic syndromes that’s characterised by low levels of HDL cholesterol, obesity, high fast aldohexose levels, hyper-trigliceridaemia and high blood pressure, by regulation of cholinergic transmission and therefore the enzyme activity within a living system. The phosphomotifs associated with amino acid and tyrosine binding motifs in AChE and BChE were known to be common. Phylogenetic tree was constructed to these proteins usinf UPGMA and Maximum Likelihood methods in MEGA software has shown interaction of AChE and BChE with ageing diseases like Alzheimer’s disease and Diabetes. AChE has shown closely related to BChE, retinol dehydrogenase and β-polypeptide. The present studies is also accomplished that AChE, BChE, COLQ, HAND1, APP, NLGN2 and NGF proteins has interactions with diseases such as Alzheimer’s and D2M using Pathwaylinker and STRING. Medicinal compounds like Ortho-7, Dibucaine and HI-6 are predicted as good targets for modeled AChE and BChE proteins based on docking studies. Hence perceptive studies of cholinesterase structure and the biological mechanisms of inhibition are necessary for effective drug development. PMID:23936743

  12. Real Time Ligand-Induced Motion Mappings of AChBP and nAChR Using X-ray Single Molecule Tracking

    PubMed Central

    Sekiguchi, Hiroshi; Suzuki, Yasuhito; Nishino, Yuri; Kobayashi, Suzuko; Shimoyama, Yoshiko; Cai, Weiyan; Nagata, Kenji; Okada, Masato; Ichiyanagi, Kouhei; Ohta, Noboru; Yagi, Naoto; Miyazawa, Atsuo; Kubo, Tai; Sasaki, Yuji C.

    2014-01-01

    We observed the dynamic three-dimensional (3D) single molecule behaviour of acetylcholine-binding protein (AChBP) and nicotinic acetylcholine receptor (nAChR) using a single molecule tracking technique, diffracted X-ray tracking (DXT) with atomic scale and 100 μs time resolution. We found that the combined tilting and twisting motions of the proteins were enhanced upon acetylcholine (ACh) binding. We present the internal motion maps of AChBP and nAChR in the presence of either ACh or α-bungarotoxin (αBtx), with views from two rotational axes. Our findings indicate that specific motion patterns represented as biaxial angular motion maps are associated with channel function in real time and on an atomic scale. PMID:25223459

  13. Kinetic evidence that desensitized nAChR may promote transitions of active nAChR to desensitized states during sustained exposure to agonists in skeletal muscle.

    PubMed

    Manthey, Arthur A

    2006-06-01

    During prolonged exposure of postjunctional nicotinic acetylcholine receptors (nAChR) of skeletal muscle to acetylcholine (ACh), agonist-activated nAChR (nAChRa) gradually fall into a refractory "desensitized" state (nAChRd), which no longer supports the high-conductance channel openings characteristic of the initially active nAChRa. In the present study, the possibility was examined that nAChRd, rather than simply constituting a passive "trap" for nAChRa, may actively promote further conversions of nAChRa to nAChRd in a formally autocatalytic manner. Single-ion whole-cell voltage-clamp currents (Na+ and Li+ in separate trials) were measured using two KCl-filled capillary electrodes (5-10 MOmega) implanted at the postjunctional locus of single frog skeletal muscle fibers (Rana pipiens) equilibrated in 30 mM K+ bath media to eliminate mechanical responses. Various nAChR agonists (carbamylcholine, acetylcholine, suberyldicholine) at different concentrations were delivered focally by positive pressure microjet. It was found that the decline of postmaximal agonist-induced currents under these different conditions (driven by the growth of the subpool of nAChRd) consistently followed an autocatalytic logistic rule modified for population growth of fixed units in a planar array: [Formula: see text] (where y represents the remaining agonist-induced current at time t, A=initial maximum current, and n is a constant). Some further experimental features that might result from a self-promoting growth of nAChRd were also tested, namely, (1) the effect of increased nAChRa and (2) the effect of increased nAChRd. Increase in agonist concentration of the superfusate, by increasing the planar density of active nAChRa at the outset, should enhance the probability of autocatalytic interactions with emerging nAChRd, hence, the rate of decline of agonist-induced current, and this was a consistent finding under all conditions tested. Raising the initial level of desensitized nAChRd by

  14. Acetylcholinesterase (AChE) and heat shock proteins (Hsp70) of gypsy moth (Lymantria dispar L.) larvae in response to long-term fluoranthene exposure.

    PubMed

    Mrdaković, Marija; Ilijin, Larisa; Vlahović, Milena; Matić, Dragana; Gavrilović, Anja; Mrkonja, Aleksandra; Perić-Mataruga, Vesna

    2016-09-01

    Polycyclic aromatic hydrocarbons (PAHs) may affect biochemical and physiological processes in living organisms, thus impairing fitness related traits and influencing their populations. This imposes the need for providing early-warning signals of pollution. Our study aimed to examine changes in the activity of acetylcholinesterase (AChE) and the concentration of heat shock proteins (Hsp70) in homogenates of brain tissues of fifth instar gypsy moth (Lymantria dispar L.) larvae, exposed to the ubiquitous PAH, fluoranthene, supplemented to the rearing diet. Significantly increased activity of AChE in larvae fed on the diets with high fluoranthene concentrations suggests the necessity for elucidation of the role of AChE in these insects when exposed to PAH pollution. Significant induction of Hsp70 in gypsy moth larvae reared on the diets containing low fluoranthene concentrations, indicate that changes in the level of Hsp70 might be useful as an indicator of pollution in this widespread forest species. PMID:27343862

  15. Acetylcholinesterase (AChE) and heat shock proteins (Hsp70) of gypsy moth (Lymantria dispar L.) larvae in response to long-term fluoranthene exposure.

    PubMed

    Mrdaković, Marija; Ilijin, Larisa; Vlahović, Milena; Matić, Dragana; Gavrilović, Anja; Mrkonja, Aleksandra; Perić-Mataruga, Vesna

    2016-09-01

    Polycyclic aromatic hydrocarbons (PAHs) may affect biochemical and physiological processes in living organisms, thus impairing fitness related traits and influencing their populations. This imposes the need for providing early-warning signals of pollution. Our study aimed to examine changes in the activity of acetylcholinesterase (AChE) and the concentration of heat shock proteins (Hsp70) in homogenates of brain tissues of fifth instar gypsy moth (Lymantria dispar L.) larvae, exposed to the ubiquitous PAH, fluoranthene, supplemented to the rearing diet. Significantly increased activity of AChE in larvae fed on the diets with high fluoranthene concentrations suggests the necessity for elucidation of the role of AChE in these insects when exposed to PAH pollution. Significant induction of Hsp70 in gypsy moth larvae reared on the diets containing low fluoranthene concentrations, indicate that changes in the level of Hsp70 might be useful as an indicator of pollution in this widespread forest species.

  16. Target site insensitivity mutations in the AChE enzyme confer resistance to organophosphorous insecticides in Leptinotarsa decemlineata (Say).

    PubMed

    Malekmohammadi, M; Galehdari, H

    2016-01-01

    In the present study, we demonstrated the use and optimization of the tetra-primer ARMS-PCR procedure to detect and analyze the frequency of the R30K and I392T mutations in resistant field populations of CPB. The R30K mutation was detected in 72%, 84%, 52% and 64% of Bahar, Dehpiaz, Aliabad and Yengijeh populations, respectively. Overall frequencies of the I392T mutation were 12%, 8% and 16% of Bahar, Aliabad and Yengijeh populations, respectively. No I392T point mutation was found among samples from Dehpiaz field population. Moreover, only 31% and 2% of samples from the resistant field populations were homozygous for R30K and I392T mutations, respectively. No individual simultaneously had both I392T and S291G/R30K point mutations. The incidence of individuals with both S291G and R30K point mutations in the samples from Bahar, Dehpiaz, Aliabad, and Yengijeh populations were 31.5%, 44.7%, 41.6%, and 27.3% respectively. Genotypes determined by the tetra-primer ARMS-PCR method were consistent with those determined by PCR sequencing. There was no significant correlation between the mutation frequencies and resistance levels in the resistant populations, indicating that other mutations may contribute to this variation. Polymorphism in the partial L. decemlineata cDNA AChE gene Ldace2 of four field populations was identified by direct sequencing of PCR-amplified fragments. Among 45 novel mutations detected in this study, T29P mutation was found across all four field populations that likely contribute to the AChE insensitivity. Site-directed mutagenesis and protein expression experiments are needed for a more complete evaluation. PMID:26778439

  17. The regulation of hippocampal nicotinic acetylcholine receptors (nAChRs) after a protracted treatment with selective or nonselective nAChR agonists.

    PubMed

    Auta, J; Longone, P; Guidotti, A; Costa, E

    1999-01-01

    In rats, 1 mg/kg twice daily for 10 d of nicotine, a nonselective agonist of nicotinic acetylcholine receptors (nAChRs), fails to change alpha4 and beta2 nAChR subunit mRNA but significantly decreased alpha7 nAChR subunit mRNA and protein expression, which is associated with a 35-40% decrease in the number of 125I-alpha-Bgtx binding sites in hippocampus. In addition, this schedule of nicotine treatment produced a 40% increase in the number of high- (K(D) 1 nM), but decreased by 25% the number of low-affinity (K(D) 30 nM) binding sites for 3H-epibatidine in hippocampus. In contrast, repeated treatment with lobeline (2.7 mg/kg twice daily for 10 d), which selectively binds to high-affinity binding nAChRs, fails to change the expression of high- or low-affinity nAChRs. These data suggest that a simultaneous upregulation of high-affinity nAChRs and downregulation of low-affinity nAChRs is elicited by ligands that can bind to both low- and high-affinity nAChRs, but not by selective agonists of high-affinity nAChRs. One might infer that in hippocampus, high- and low-affinity nAChRs may be located in the same cells. When these two receptor types are stimulated simultaneously by nonselective ligands for high- and low-affinity nAChRs, they interact, bringing about an increase in binding site density of the high-affinity nAChRs.

  18. Novel bis-(−)-nor-meptazinol derivatives act as dual binding site AChE inhibitors with metal-complexing property

    SciTech Connect

    Zheng, Wei; Li, Juan; Qiu, Zhuibai; Xia, Zheng; Li, Wei; Yu, Lining; Chen, Hailin; Chen, Jianxing; Chen, Yan; Hu, Zhuqin; Zhou, Wei; Shao, Biyun; Cui, Yongyao; Xie, Qiong; Chen, Hongzhuan

    2012-10-01

    The strategy of dual binding site acetylcholinesterase (AChE) inhibition along with metal chelation may represent a promising direction for multi-targeted interventions in the pathophysiological processes of Alzheimer's disease (AD). In the present study, two derivatives (ZLA and ZLB) of a potent dual binding site AChE inhibitor bis-(−)-nor-meptazinol (bis-MEP) were designed and synthesized by introducing metal chelating pharmacophores into the middle chain of bis-MEP. They could inhibit human AChE activity with IC{sub 50} values of 9.63 μM (for ZLA) and 8.64 μM (for ZLB), and prevent AChE-induced amyloid-β (Aβ) aggregation with IC{sub 50} values of 49.1 μM (for ZLA) and 55.3 μM (for ZLB). In parallel, molecular docking analysis showed that they are capable of interacting with both the catalytic and peripheral anionic sites of AChE. Furthermore, they exhibited abilities to complex metal ions such as Cu(II) and Zn(II), and inhibit Aβ aggregation triggered by these metals. Collectively, these results suggest that ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency, and may be potential leads of value for further study on disease-modifying treatment of AD. -- Highlights: ► Two novel bis-(−)-nor-meptazinol derivatives are designed and synthesized. ► ZLA and ZLB may act as dual binding site AChEIs with metal-chelating potency. ► They are potential leads for disease-modifying treatment of Alzheimer's disease.

  19. Chlorpyrifos and Malathion have opposite effects on behaviors and brain size that are not correlated to changes in AChE activity

    PubMed Central

    Richendrfer, Holly; Creton, Robbert

    2015-01-01

    Organophosphates, a type of neurotoxicant pesticide, are used globally for the treatment of pests on croplands and are therefore found in a large number of conventional foods. These pesticides are harmful and potentially deadly if ingested or inhaled in large quantities by causing a significant reduction in acetylcholinesterase (AChE) activity in the central and peripheral nervous system. However, much less is known about the effects of exposure to small quantities of the pesticides on neural systems and behavior during development. In the current study we used zebrafish larvae in order to determine the effects of two of the most widely used organophosphates, chlorpyrifos and malathion, on zebrafish behavior and AChE activity. Embryos and larvae were exposed to the organophosphates during different time points in development and then tested at 5 days post-fertilization for behavioral, neurodevelopmental and AChE abnormalities. The results of the study indicate that chlorpyrifos and malathion cause opposing behaviors in the larvae such as swim speed (hypoactivity vs. hyperactivity) and rest. Additionally, the pesticides affect only certain behaviors, such as thigmotaxis, during specific time points in development that are unrelated to changes in AChE activity. Larvae treated with malathion but not chlorpyrifos also had significantly smaller forebrain and hindbrain regions compared to controls by 5 days post-fertilization. We conclude that exposure to very low concentrations of organophosphate pesticides during development cause abnormalities in behavior and brain size. PMID:25983063

  20. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward.

    PubMed

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; Nichols, Weston A; Moaddel, Ruin; Xiao, Cheng; Lester, Henry A

    2016-03-01

    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway.

  1. Auxofuran, a Novel Metabolite That Stimulates the Growth of Fly Agaric, Is Produced by the Mycorrhiza Helper Bacterium Streptomyces Strain AcH 505†

    PubMed Central

    Riedlinger, Julia; Schrey, Silvia D.; Tarkka, Mika T.; Hampp, Rüdiger; Kapur, Manmohan; Fiedler, Hans-Peter

    2006-01-01

    The mycorrhiza helper bacterium Streptomyces strain AcH 505 improves mycelial growth of ectomycorrhizal fungi and formation of ectomycorrhizas between Amanita muscaria and spruce but suppresses the growth of plant-pathogenic fungi, suggesting that it produces both fungal growth-stimulating and -suppressing compounds. The dominant fungal-growth-promoting substance produced by strain AcH 505, auxofuran, was isolated, and its effect on the levels of gene expression of A. muscaria was investigated. Auxofuran and its synthetic analogue 7-dehydroxy-auxofuran were most effective at a concentration of 15 μM, and application of these compounds led to increased lipid metabolism-related gene expression. Cocultivation of strain AcH 505 and A. muscaria stimulated auxofuran production by the streptomycete. The antifungal substances produced by strain AcH 505 were identified as the antibiotics WS-5995 B and C. WS-5995 B completely blocked mycelial growth at a concentration of 60 μM and caused a cell stress-related gene expression response in A. muscaria. Characterization of these compounds provides the foundation for molecular analysis of the fungus-bacterium interaction in the ectomycorrhizal symbiosis between fly agaric and spruce. PMID:16672502

  2. Escherichia coli Protein Expression System for Acetylcholine Binding Proteins (AChBPs)

    PubMed Central

    Abraham, Nikita; Paul, Blessy; Ragnarsson, Lotten; Lewis, Richard J.

    2016-01-01

    Nicotinic acetylcholine receptors (nAChR) are ligand gated ion channels, identified as therapeutic targets for a range of human diseases. Drug design for nAChR related disorders is increasingly using structure-based approaches. Many of these structural insights for therapeutic lead development have been obtained from co-crystal structures of nAChR agonists and antagonists with the acetylcholine binding protein (AChBP). AChBP is a water soluble, structural and functional homolog of the extracellular, ligand-binding domain of nAChRs. Currently, AChBPs are recombinantly expressed in eukaryotic expression systems for structural and biophysical studies. Here, we report the establishment of an Escherichia coli (E. coli) expression system that significantly reduces the cost and time of production compared to the existing expression systems. E. coli can efficiently express unglycosylated AChBP for crystallography and makes the expression of isotopically labelled forms feasible for NMR. We used a pHUE vector containing an N-terminal His-tagged ubiquitin fusion protein to facilitate AChBP expression in the soluble fractions, and thus avoid the need to recover protein from inclusion bodies. The purified protein yield obtained from the E. coli expression system is comparable to that obtained from existing AChBP expression systems. E. coli expressed AChBP bound nAChR agonists and antagonists with affinities matching those previously reported. Thus, the E. coli expression system significantly simplifies the expression and purification of functional AChBP for structural and biophysical studies. PMID:27304486

  3. Phe362Tyr in AChE: A Major Factor Responsible for Azamethiphos Resistance in Lepeophtheirus salmonis in Norway

    PubMed Central

    Kaur, Kiranpreet; Jansen, Peder Andreas; Aspehaug, Vidar Teis; Horsberg, Tor Einar

    2016-01-01

    Organophosphates (OP) are one of the major treatments used against the salmon louse (Lepeophtherius salmonis) in Norwegian salmonid aquaculture. The use of OP since the late 1970s has resulted in widespread resistant parasites. Recently, we reported a single mutation (Phe362Tyr) in acetylcholinesterase (AChE) as the major mechanism behind resistance in salmon louse towards OP. The present study was carried out to validate this mechanism at the field level. A total of 6658 salmon louse samples were enrolled from 56 different fish farms across the Norwegian coast, from Vest Agder in the south to Finnmark in the north. All the samples were genotyped using a TaqMan probe assay for the Phe362Tyr mutation. A strong association was observed between areas with frequent use of the OP (azamethiphos) and the Phe362Tyr mutation. This was confirmed at 15 sites where results from independently conducted bioassays and genotyping of parasites correlated well. Furthermore, genotyping of surviving and moribund parasites from six bioassay experiments demonstrated a highly significant negative correlation between the frequency of resistance alleles and the probability of dying when exposed to azamethiphos in a bioassay. Based on these observations, we could strongly conclude that the Phe362Tyr mutation is a major factor responsible for OP resistance in salmon louse on Norwegian fish farms. PMID:26882536

  4. Phe362Tyr in AChE: A Major Factor Responsible for Azamethiphos Resistance in Lepeophtheirus salmonis in Norway.

    PubMed

    Kaur, Kiranpreet; Jansen, Peder Andreas; Aspehaug, Vidar Teis; Horsberg, Tor Einar

    2016-01-01

    Organophosphates (OP) are one of the major treatments used against the salmon louse (Lepeophtherius salmonis) in Norwegian salmonid aquaculture. The use of OP since the late 1970s has resulted in widespread resistant parasites. Recently, we reported a single mutation (Phe362Tyr) in acetylcholinesterase (AChE) as the major mechanism behind resistance in salmon louse towards OP. The present study was carried out to validate this mechanism at the field level. A total of 6658 salmon louse samples were enrolled from 56 different fish farms across the Norwegian coast, from Vest Agder in the south to Finnmark in the north. All the samples were genotyped using a TaqMan probe assay for the Phe362Tyr mutation. A strong association was observed between areas with frequent use of the OP (azamethiphos) and the Phe362Tyr mutation. This was confirmed at 15 sites where results from independently conducted bioassays and genotyping of parasites correlated well. Furthermore, genotyping of surviving and moribund parasites from six bioassay experiments demonstrated a highly significant negative correlation between the frequency of resistance alleles and the probability of dying when exposed to azamethiphos in a bioassay. Based on these observations, we could strongly conclude that the Phe362Tyr mutation is a major factor responsible for OP resistance in salmon louse on Norwegian fish farms. PMID:26882536

  5. BrightFocus Foundation

    MedlinePlus

    ... Alzheimer’s Disease Research Program Macular Degeneration Research Program National Glaucoma Research Program Molecular Neurodegeneration ... Foundation BrightFocus Foundation 22512 Gateway Center Drive Clarksburg, MD ...

  6. Proteus Syndrome Foundation

    MedlinePlus

    ... Criteria & FAQs Medical Research Glossary Donate Cash Donation Life Insurance Gift Matching Gift Stock Gift Sunshine Society Contact Privacy Policy Proteus Syndrome Foundation The Proteus Syndrome Foundation , a ...

  7. α7nAchR/NMDAR coupling affects NMDAR function and object recognition.

    PubMed

    Li, Shupeng; Nai, Qiang; Lipina, Tatiana V; Roder, John C; Liu, Fang

    2013-12-20

    The α7 nicotinic acetylcholine receptor (nAchR) and NMDA glutamate receptor (NMDAR) are both ligand-gated ion channels permeable to Ca2+ and Na+. Previous studies have demonstrated functional modulation of NMDARs by nAchRs, although the molecular mechanism remains largely unknown. We have previously reported that α7nAchR forms a protein complex with the NMDAR through a protein-protein interaction. We also developed an interfering peptide that is able to disrupt the α7nAchR-NMDAR complex and blocks cue-induced reinstatement of nicotine-seeking in rat models of relapse. In the present study, we investigated whether the α7nAchR-NMDAR interaction is responsible for the functional modulation of NMDAR by α7nAchR using both electrophysiological and behavioral tests. We have found that activation of α7nAchR upregulates NMDAR-mediated whole cell currents and LTP of mEPSC in cultured hippocampal neurons, which can be abolished by the interfering peptide that disrupts the α7nAchR-NMDAR interaction. Moreover, administration of the interfering peptide in mice impairs novel object recognition but not Morris water maze performance. Our results suggest that α7nAchR/NMDAR coupling may selectively affect some aspects of learning and memory.

  8. Clinical application of clustered-AChR for the detection of SNMG

    PubMed Central

    Zhao, Guang; Wang, Xiaoqing; Yu, Xiaowen; Zhang, Xiutian; Guan, Yangtai; Jiang, Jianming

    2015-01-01

    Myasthenia gravis (MG) is an autoantibody-mediated disease of the neuromuscular junction (NMJ). However, accumulating evidence has indicated that MG patients whose serum anti-acetylcholine receptor (AChR) antibodies are not detectable (serumnegative MG; SNMG) in routine assays share similar clinical features with anti-AChR antibody-positive MG patients. We hypothesized that SNMG patients would have low-affinity antibodies to AChRs that would not be detectable using traditional methods but that might be detected by binding to AChR on the cell membrane, particularly if they were clustered at the high density observed at the NMJ. We expressed AChR subunits with the clustering protein rapsyn (an AChR-associated protein at the synapse) in human embryonic kidney (HEK) cells, and we tested the binding of the antibodies using immunofluorescence. With this approach, AChR antibodies to rapsyn-clustered AChR could be detected in the sera from 45.83% (11/24) of SNMG patients, as confirmed with fluorescence-activated cell sorting (FACS). This was the first application in China of cell-based AChR antibody detection. More importantly, this sensitive (and specific) approach could significantly increase the diagnosis rate of SNMG. PMID:26068604

  9. Menthol Alone Upregulates Midbrain nAChRs, Alters nAChR Subtype Stoichiometry, Alters Dopamine Neuron Firing Frequency, and Prevents Nicotine Reward

    PubMed Central

    Henderson, Brandon J.; Wall, Teagan R.; Henley, Beverley M.; Kim, Charlene H.; Nichols, Weston A.; Moaddel, Ruin; Xiao, Cheng

    2016-01-01

    Upregulation of β2 subunit-containing (β2*) nicotinic acetylcholine receptors (nAChRs) is implicated in several aspects of nicotine addiction, and menthol cigarette smokers tend to upregulate β2* nAChRs more than nonmenthol cigarette smokers. We investigated the effect of long-term menthol alone on midbrain neurons containing nAChRs. In midbrain dopaminergic (DA) neurons from mice containing fluorescent nAChR subunits, menthol alone increased the number of α4 and α6 nAChR subunits, but this upregulation did not occur in midbrain GABAergic neurons. Thus, chronic menthol produces a cell-type-selective upregulation of α4* nAChRs, complementing that of chronic nicotine alone, which upregulates α4 subunit-containing (α4*) nAChRs in GABAergic but not DA neurons. In mouse brain slices and cultured midbrain neurons, menthol reduced DA neuron firing frequency and altered DA neuron excitability following nAChR activation. Furthermore, menthol exposure before nicotine abolished nicotine reward-related behavior in mice. In neuroblastoma cells transfected with fluorescent nAChR subunits, exposure to 500 nm menthol alone also increased nAChR number and favored the formation of (α4)3(β2)2 nAChRs; this contrasts with the action of nicotine itself, which favors (α4)2(β2)3 nAChRs. Menthol alone also increases the number of α6β2 receptors that exclude the β3 subunit. Thus, menthol stabilizes lower-sensitivity α4* and α6 subunit-containing nAChRs, possibly by acting as a chemical chaperone. The abolition of nicotine reward-related behavior may be mediated through menthol's ability to stabilize lower-sensitivity nAChRs and alter DA neuron excitability. We conclude that menthol is more than a tobacco flavorant: administered alone chronically, it alters midbrain DA neurons of the nicotine reward-related pathway. SIGNIFICANCE STATEMENT Menthol, the most popular flavorant for tobacco products, has been considered simply a benign flavor additive. However, as we show here

  10. Extracts and constituents of Leontopodium alpinum enhance cholinergic transmission: Brain ACh increasing and memory improving properties

    PubMed Central

    Hornick, Ariane; Schwaiger, Stefan; Rollinger, Judith M.; Vo, Nguyen Phung; Prast, Helmut; Stuppner, Hermann

    2012-01-01

    Leontopodium alpinum (‘Edelweiss’) was phytochemically investigated for constituents that might enhance cholinergic neurotransmission. The potency to increase synaptic availability of acetylcholine (ACh) in rat brain served as key property for the bioguided isolation of cholinergically active compounds using different chromatographic techniques. The dichlormethane (DCM) extract of the root, fractions and isolated constituents were injected i.c.v. and the effect on brain ACh was detected via the push–pull technique. The DCM extract enhanced extracellular ACh concentration in rat brain and inhibited acetylcholinesterase (AChE) in vitro. The extracellular level of brain ACh was significantly increased by the isolated sesquiterpenes, isocomene and 14-acetoxyisocomene, while silphiperfolene acetate and silphinene caused a small increasing tendency. Only silphiperfolene acetate showed in vitro AChE inhibitory activity, thus suggesting the other sesquiterpenes to stimulate cholinergic transmission by an alternative mechanism of action. Isocomene was further investigated with behavioural tasks in mice. It restored object recognition in scopolamine-impaired mice and showed nootropic effects in the T-maze alternation task in normal and scopolamine-treated mice. Additionally, this sesquiterpene reduced locomotor activity of untreated mice in the open field task, while the activity induced by scopolamine was abolished. The enhancement of synaptic availability of ACh, the promotion of alternation, and the amelioration of scopolamine-induced deficit are in accordance with a substance that amplifies cholinergic transmission. Whether the mechanism of action is inhibition of AChE or another pro-cholinergic property remains to be elucidated. Taken together, isocomene and related constituents of L. alpinum deserve further interest as potential antidementia agents in brain diseases associated with cholinergic deficits. PMID:18541221

  11. Analysis of free ACh and 5-HT in milk from four different species and their bioactivity on 5-HT(3) and nACh receptors.

    PubMed

    Gallegos-Perez, Jose-Luis; Limon, Agenor; Reyes-Ruiz, Jorge M; Alshanqeeti, Ali S; Aljohi, Mohammad A; Miledi, Ricardo

    2014-07-25

    Milk is one of the most beneficial aliments and is highly recommended in normal conditions; however, in certain disorders, like irritable bowel syndrome, cow milk and dairy products worsen the gastric symptoms and their use is not recommended. Among the most recognized milk-induced gatrointestinal symptoms are abdominal pain, nausea and vomiting, which are processes controlled by cholinergic and serotonergic transmission. Whether the presence of bioavailable ACh and 5-HT in milk may contribute to normal peristalsis, or to the developing of these symptoms, is not known. In this work we attempt to determine whether the content of free ACh and 5-HT is of physiological significance in milk from four different species: cow (bovine), goat, camel and human. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) was used to identify and quantify free ACh and 5-HT in milk, and activation of the serotonergic and cholinergic ionotropic receptors was investigated using electrophysiological experiments. Our principal hypothesis was that milk from these four species had sufficient free ACh and 5-HT to activate their correspondent receptors expressed in a heterologous system. Our results showed a more complex picture, in which free ACh and 5-HT and their ability to activate cholinergic and serotonergic receptors are not correlated. This work is a first step to elucidate whether 5-HT and ACh, at the concentrations present in the milk, can be associated to a direct function in the GI.

  12. Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies.

    PubMed

    Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Martínez-Ramos, Federico; Padilla-Martínez, Itzia Irene; Benítez-Cardoza, Claudia G; Mera-Jiménez, Elvia; Rosales-Hernández, Martha Cecilia

    2014-01-01

    Despite great efforts to develop new therapeutic strategies against Alzheimer's disease (AD), the acetylcholinesterase inhibitors (AChEIs): donepezil, rivastigmine, and galantamine, have been used only as a palliative therapeutic approach. However, the pathogenesis of AD includes several factors such as cholinergic hypothesis, amyloid-β (Aβ) aggregation, and oxidative stress. For this reason, the design of compounds that target the genesis and progression of AD could offer a therapeutic benefit. We have designed a set of compounds (M-1 to M-5) with pharmacophore moieties to inhibit the release, aggregation, or toxicity of Aβ, act as AChEIs and have antioxidant properties. Once the compounds were designed, we analyzed their physicochemical parameters and performed docking studies to determine their affinity values for AChE, β-site amyloid-protein precursor cleaving enzyme 1 (BACE1), and the Aβ monomer. The best ligands, M-1 and M-4, were then synthesized, chemically characterized, and evaluated in vitro. The in vitro studies showed that these compounds inhibit AChE (M-1 Ki = 0.12 and M-4 Ki = 0.17 μM) and BACE1 (M-1 IC50 = 15.1 and M-4 IC50 = 15.4 nM). They also inhibit Aβ oligomerization and exhibit antioxidant activity. In addition, these compounds showed low cytotoxicity in microglial cells. For these reasons, they are promising for future use as drugs in AD mice transgenic models.

  13. Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies.

    PubMed

    Hernández-Rodríguez, Maricarmen; Correa-Basurto, José; Martínez-Ramos, Federico; Padilla-Martínez, Itzia Irene; Benítez-Cardoza, Claudia G; Mera-Jiménez, Elvia; Rosales-Hernández, Martha Cecilia

    2014-01-01

    Despite great efforts to develop new therapeutic strategies against Alzheimer's disease (AD), the acetylcholinesterase inhibitors (AChEIs): donepezil, rivastigmine, and galantamine, have been used only as a palliative therapeutic approach. However, the pathogenesis of AD includes several factors such as cholinergic hypothesis, amyloid-β (Aβ) aggregation, and oxidative stress. For this reason, the design of compounds that target the genesis and progression of AD could offer a therapeutic benefit. We have designed a set of compounds (M-1 to M-5) with pharmacophore moieties to inhibit the release, aggregation, or toxicity of Aβ, act as AChEIs and have antioxidant properties. Once the compounds were designed, we analyzed their physicochemical parameters and performed docking studies to determine their affinity values for AChE, β-site amyloid-protein precursor cleaving enzyme 1 (BACE1), and the Aβ monomer. The best ligands, M-1 and M-4, were then synthesized, chemically characterized, and evaluated in vitro. The in vitro studies showed that these compounds inhibit AChE (M-1 Ki = 0.12 and M-4 Ki = 0.17 μM) and BACE1 (M-1 IC50 = 15.1 and M-4 IC50 = 15.4 nM). They also inhibit Aβ oligomerization and exhibit antioxidant activity. In addition, these compounds showed low cytotoxicity in microglial cells. For these reasons, they are promising for future use as drugs in AD mice transgenic models. PMID:24762947

  14. THE ACHES THAT TAKE YOUR BREATH (AND TEARS) AWAY.

    PubMed

    Becerril, J; Gonzales, H; Saketkoo, L A

    2015-01-01

    An 80-year-old man presented with a complaint of three months of fatigue and aching of his shoulders and hips, as well as pain, swelling, and stiffness in bilateral fingers that was worse in the morning but improved with movement. Associated symptoms included worsening dry mouth and eyes, dysphagia, exertional dyspnea, and right foot drop. Physical exam was significant for edematous and tender bilateral proximal interphalangeal joints, metacarpophalangeal joints and wrists with decreased grip, extension and flexion, as well as bilateral pulmonary crackles. Laboratory analysis revealed Anti-Ro (SSA) and Anti-La (SSB) positivity with elevated erythrocyte sedimentation rate (70mm/hr) and C-reactive peptide (13mg/L). Pulmonary function testing was notable for a forced vital capacity (FVC) of 64% and carbon monoxide diffusing capacity (DLCO) of 44%. High resolution chest computed tomography demonstrated fibrotic changes consistent with nonspecific interstitial pneumonitis. The patient was started on mycophenolate mofetil, hydroxychloroquine, and prednisone for Sjögren's syndrome (SjS). Symptoms improved and repeat FVC revealed a 20 percent improvement, however subsequent tapering of prednisone resulted in worsening dyspnea and increase of FVC to 60 prcent. Prednisone was restarted and rituximab 2g divided in two doses was administered with overall symptom improvement. Symptoms and FVC continued to wax and wane over the following 18 months requiring re-dosing of rituximab with most recent FVC improved to 71 percent and DLCO 41 percent. PMID:27159479

  15. Children's Tumor Foundation

    MedlinePlus

    ... The Children’s Tumor Foundation and Vice President Biden’s National Cancer Moonshot Initiative Oct 26, 2016, Posted in Collaborations , Latest News , Press Release , Science Foundation President Annette Bakker Participates in Key Meetings Dedicated ...

  16. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Cancer Foundation joins the PBTF Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  17. Restless Legs Syndrome Foundation

    MedlinePlus

    ... Syndrome Foundation is a registered 501(c)3 non-profit corporation (Tax ID #56-1784846). Donations are tax- ... Syndrome Foundation is a registered 501(c)3 non-profit corporation (Tax ID #56-1784846). Donations are tax- ...

  18. Oral Cancer Foundation

    MedlinePlus

    ... Famous People Famous historical Arts & Entertainment Sports figures ... The Oral Cancer Foundation The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering ...

  19. Kessler Foundation Research Center

    MedlinePlus

    ... Mindfulness-based Therapy in Children and Adolescents with Brain Injury Dr. Zanca of Kessler Foundation Receives $600,000 ... to Improve Learning among Children and Adolescents with Brain Injury Kessler Foundation Seeks Children and Adolescents for Brain ...

  20. Parkinson's Disease Foundation Newsletter

    MedlinePlus

    ... Newsletters These include monthly e-newsletters and quarterly science-specific e-newsletters. Read the latest issue below or browse the archives. National Parkinson Foundation and the Parkinson’s Disease Foundation Complete Merger to ...

  1. Ni nanoparticle catalyzed growth of MWCNTs on Cu NPs @ a-C:H substrate

    NASA Astrophysics Data System (ADS)

    Ghodselahi, T.; Solaymani, S.; Akbarzadeh Pasha, M.; Vesaghi, M. A.

    2012-11-01

    NiCu NPs @ a-C:H thin films with different Cu content were prepared by co-deposition by RF-sputtering and RF-plasma enhanced chemical vapor deposition (RF-PECVD) from acetylene gas and Cu and Ni targets. The prepared samples were used as catalysts for growing multi-wall carbon nanotubes (MWCNTs) from liquid petroleum gas (LPG) at 825 °C by thermal chemical vapor deposition (TCVD). By addition of Cu NPs @ a-C:H thin layer as substrate for Ni NPs catalyst, the density of the grown CNTs is greatly enhanced in comparison to bare Si substrate. Furthermore the average diameter of the grown CNTs decreases by decreasing of Cu content of Cu NPs @ a-C:H thin layer. However Cu NPs @ a-C:H by itself has no catalytic property in MWCNTs growth. Morphology and electrical and optical properties of Cu NPs @ a-C:H thin layer is affected by Cu content and each of them is effective parameter on growth of MWCNTs based on Ni NPs catalyst. Moreover, adding of a low amount of Ni NPs doesn't vary optical, electrical and morphology properties of Cu NPs @ a-C:H thin layer but it has a profound effect on its catalytic activity. Finally the density and diameter of MWCNTs can be optimized by selection of the Cu NPs @ a-C:H thin layer as substrate of Ni NPs.

  2. mAChRs activation induces epithelial-mesenchymal transition on lung epithelial cells

    PubMed Central

    2014-01-01

    Background Epithelial-mesenchymal transition (EMT) has been proposed as a mechanism in the progression of airway diseases and cancer. Here, we explored the role of acetylcholine (ACh) and the pathway involved in the process of EMT, as well as the effects of mAChRs antagonist. Methods Human lung epithelial cells were stimulated with carbachol, an analogue of ACh, and epithelial and mesenchymal marker proteins were evaluated using western blot and immunofluorescence analyses. Results Decreased E-cadherin expression and increased vimentin and α-SMA expression induced by TGF-β1 in alveolar epithelial cell (A549) were significantly abrogated by the non-selective mAChR antagonist atropine and enhanced by the acetylcholinesterase inhibitor physostigmine. An EMT event also occurred in response to physostigmine alone. Furthermore, ChAT express and ACh release by A549 cells were enhanced by TGF-β1. Interestingly, ACh analogue carbachol also induced EMT in A549 cells as well as in bronchial epithelial cells (16HBE) in a time- and concentration-dependent manner, the induction of carbachol was abrogated by selective antagonist of M1 (pirenzepine) and M3 (4-DAMP) mAChRs, but not by M2 (methoctramine) antagonist. Moreover, carbachol induced TGF-β1 production from A549 cells concomitantly with the EMT process. Carbachol-induced EMT occurred through phosphorylation of Smad2/3 and ERK, which was inhibited by pirenzepine and 4-DAMP. Conclusions Our findings for the first time indicated that mAChR activation, perhaps via M1 and M3 mAChR, induced lung epithelial cells to undergo EMT and provided insights into novel therapeutic strategies for airway diseases in which lung remodeling occurs. PMID:24678619

  3. Remarkably increased resistin levels in anti-AChR antibody-positive myasthenia gravis.

    PubMed

    Zhang, Da-Qi; Wang, Rong; Li, Ting; Li, Xin; Qi, Yuan; Wang, Jing; Yang, Li

    2015-06-15

    Resistin is a pro-inflammatory cytokine involved in the pathogenesis of autoimmune diseases. To investigate serum resistin levels in patients with myasthenia gravis (MG) and determine if there are associations between resistin levels and disease severity, we measured serum resistin levels in 102 patients with anti-acetylcholine receptor antibody-positive MG (AChR-MG). We further analyzed associations between serum resistin levels and clinical variables in patients with MG. Our findings demonstrate that serum resistin levels are elevated in patients with AChR-generalized MG and AChR-MG with thymoma and are correlated with disease severity. Resistin has potential as a useful serum biomarker for inflammation in AChR-MG.

  4. Lymphocyte-derived ACh regulates local innate but not adaptive immunity

    PubMed Central

    Reardon, Colin; Duncan, Gordon S.; Brüstle, Anne; Brenner, Dirk; Tusche, Michael W.; Olofsson, Peder S.; Rosas-Ballina, Mauricio; Tracey, Kevin J.; Mak, Tak W.

    2013-01-01

    Appropriate control of immune responses is a critical determinant of health. Here, we show that choline acetyltransferase (ChAT) is expressed and ACh is produced by B cells and other immune cells that have an impact on innate immunity. ChAT expression occurs in mucosal-associated lymph tissue, subsequent to microbial colonization, and is reduced by antibiotic treatment. MyD88-dependent Toll-like receptor up-regulates ChAT in a transient manner. Unlike the previously described CD4+ T-cell population that is stimulated by norepinephrine to release ACh, ChAT+ B cells release ACh after stimulation with sulfated cholecystokinin but not norepinephrine. ACh-producing B-cells reduce peritoneal neutrophil recruitment during sterile endotoxemia independent of the vagus nerve, without affecting innate immune cell activation. Endothelial cells treated with ACh in vitro reduced endothelial cell adhesion molecule expression in a muscarinic receptor-dependent manner. Despite this ability, ChAT+ B cells were unable to suppress effector T-cell function in vivo. Therefore, ACh produced by lymphocytes has specific functions, with ChAT+ B cells controlling the local recruitment of neutrophils. PMID:23297238

  5. From crystal structure of α-conotoxin GIC in complex with Ac-AChBP to molecular determinants of its high selectivity for α3β2 nAChR

    PubMed Central

    Lin, Bo; Xu, Manyu; Zhu, Xiaopeng; Wu, Yong; Liu, Xi; Zhangsun, Dongting; Hu, Yuanyan; Xiang, Shi-Hua; Kasheverov, Igor E.; Tsetlin, Victor I.; Wang, Xinquan; Luo, Sulan

    2016-01-01

    Acetylcholine binding proteins (AChBPs) are unique spatial homologs of the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), and they reproduce some pharmacological properties of nAChRs. X-ray crystal structures of AСhBP in complex with α-conotoxins provide important insights into the interactions of α-conotoxins with distinct nAChR subtypes. Although considerable efforts have been made to understand why α-conotoxin GIC is strongly selective for α3β2 nAChR, this question has not yet been solved. Here we present the structure of α-conotoxin GIC in complex with Aplysia californica AChBP (Ac-AChBP) at a resolution of 2.1 Å. Based on this co-crystal structure complemented with molecular docking data, we suggest the key residues of GIC in determining its high affinity and selectivity for human α3β2 vs α3β4 nAChRs. These suggestions were checked by radioligand and electrophysiology experiments, which confirmed the functional role of detected contacts for GIC interactions with Ac-AChBP and α3β2 nAChR subtypes. While GIC elements responsible for its high affinity binding with Ac-AChBP and α3β2 nAChR were identified, our study also showed the limitations of computer modelling in extending the data from the X-ray structures of the AChBP complexes to all nAChR subtypes. PMID:26925840

  6. American Macular Degeneration Foundation

    MedlinePlus

    ... to content Contact DONATE Search for: Search Saving sight through research and education American Macular Degeneration Foundation Saving Sight Through Research and Education Menu About Macular Degeneration ...

  7. Foundation Design Handbook

    SciTech Connect

    Carmody, John; Mosiman, Garrett; Handeen, Daniel; Huelman, Patrick; Christian, Jeffery

    2013-10-01

    The purpose of this handbook is to provide information that will enable designers, builders, and homeowners to understand foundation design problems and solutions. The foundation of a house is a somewhat invisible and sometimes ignored component of the building. It is increasingly evident, however, that attention to good foundation design and construction has significant benefits to the homeowner and the builder, and can avoid some serious future problems. Good foundation design and construction practice means not only insulating to save energy, but also providing effective structural design as well as moisture, termite, and radon control techniques where appropriate.

  8. Osteogenesis Imperfecta Foundation

    MedlinePlus

    ... Foundation provides medically verified information to families and healthcare professionals, funds new OI research and promotes public policy that supports people living with osteogenesis imperfecta. Learn ...

  9. Functional Human α7 Nicotinic Acetylcholine Receptor (nAChR) Generated from Escherichia coli.

    PubMed

    Tillman, Tommy S; Alvarez, Frances J D; Reinert, Nathan J; Liu, Chuang; Wang, Dawei; Xu, Yan; Xiao, Kunhong; Zhang, Peijun; Tang, Pei

    2016-08-26

    Human Cys-loop receptors are important therapeutic targets. High-resolution structures are essential for rational drug design, but only a few are available due to difficulties in obtaining sufficient quantities of protein suitable for structural studies. Although expression of proteins in E. coli offers advantages of high yield, low cost, and fast turnover, this approach has not been thoroughly explored for full-length human Cys-loop receptors because of the conventional wisdom that E. coli lacks the specific chaperones and post-translational modifications potentially required for expression of human Cys-loop receptors. Here we report the successful production of full-length wild type human α7nAChR from E. coli Chemically induced chaperones promote high expression levels of well-folded proteins. The choice of detergents, lipids, and ligands during purification determines the final protein quality. The purified α7nAChR not only forms pentamers as imaged by negative-stain electron microscopy, but also retains pharmacological characteristics of native α7nAChR, including binding to bungarotoxin and positive allosteric modulators specific to α7nAChR. Moreover, the purified α7nAChR injected into Xenopus oocytes can be activated by acetylcholine, choline, and nicotine, inhibited by the channel blockers QX-222 and phencyclidine, and potentiated by the α7nAChR specific modulators PNU-120596 and TQS. The successful generation of functional human α7nAChR from E. coli opens a new avenue for producing mammalian Cys-loop receptors to facilitate structure-based rational drug design. PMID:27385587

  10. Foundations for Critical Thinking

    ERIC Educational Resources Information Center

    Bers, Trudy; Chun, Marc; Daly, William T.; Harrington, Christine; Tobolowsky, Barbara F.

    2015-01-01

    "Foundations for Critical Thinking" explores the landscape of critical-thinking skill development and pedagogy through foundational chapters and institutional case studies involving a range of students in diverse settings. By establishing a link between active learning and improved critical thinking, this resource encourages all higher…

  11. Foundation Development Abstracts, 1991.

    ERIC Educational Resources Information Center

    Anderson, James M., Ed.

    1991-01-01

    This series of brief two-page essays is published quarterly by the Network of California Community College Foundations to address topics related to development activities typically conducted by educational foundations. Volume 1 includes "Your Message is as Clear as Your Mission Statement," by Pat Rasmussen and James M. Anderson, which suggests…

  12. Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

    PubMed

    Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

    2015-08-01

    Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis.

  13. Identification and Expression of Acetylcholinesterase in Octopus vulgaris Arm Development and Regeneration: a Conserved Role for ACHE?

    PubMed

    Fossati, Sara Maria; Candiani, Simona; Nödl, Marie-Therese; Maragliano, Luca; Pennuto, Maria; Domingues, Pedro; Benfenati, Fabio; Pestarino, Mario; Zullo, Letizia

    2015-08-01

    Acetylcholinesterase (ACHE) is a glycoprotein with a key role in terminating synaptic transmission in cholinergic neurons of both vertebrates and invertebrates. ACHE is also involved in the regulation of cell growth and morphogenesis during embryogenesis and regeneration acting through its non-cholinergic sites. The mollusk Octopus vulgaris provides a powerful model for investigating the mechanisms underlying tissue morphogenesis due to its high regenerative power. Here, we performed a comparative investigation of arm morphogenesis during adult arm regeneration and embryonic arm development which may provide insights on the conserved ACHE pathways. In this study, we cloned and characterized O. vulgaris ACHE, finding a single highly conserved ACHE hydrophobic variant, characterized by prototypical catalytic sites and a putative consensus region for a glycosylphosphatidylinositol (GPI)-anchor attachment at the COOH-terminus. We then show that its expression level is correlated to the stage of morphogenesis in both adult and embryonic arm. In particular, ACHE is localized in typical neuronal sites when adult-like arm morphology is established and in differentiating cell locations during the early stages of arm morphogenesis. This possibility is also supported by the presence in the ACHE sequence and model structure of both cholinergic and non-cholinergic sites. This study provides insights into ACHE conserved roles during processes of arm morphogenesis. In addition, our modeling study offers a solid basis for predicting the interaction of the ACHE domains with pharmacological blockers for in vivo investigations. We therefore suggest ACHE as a target for the regulation of tissue morphogenesis. PMID:25112677

  14. Atomic interactions of neonicotinoid agonists with AChBP: Molecular recognition of the distinctive electronegative pharmacophore

    SciTech Connect

    Talley, Todd T.; Harel, Michal; Hibbs, Ryan E.; Radi, Zoran; Tomizawa, Motohiro; Casida, John E.; Taylor, Palmer

    2008-07-28

    Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 {angstrom} in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids.

  15. Builder's foundation handbook

    SciTech Connect

    Carmody, J. . Underground Space Center); Christian, J. ); Labs, K. )

    1991-05-01

    This handbook contains a worksheet for selecting insulation levels based on specific building construction, climate, HVAC equipment, insulation cost, and other economic considerations. The worksheet permits optimization of foundation insulation levels for new or retrofit applications. Construction details representing good practices for the design and installation of energy efficient basement, crawl space, and slab-n-grade foundations are the focal point of the handbook. The construction details are keyed to lists of critical design information useful for specifying structural integrity; thermal and vapor control; subsurface drainage; waterproofing; and mold, mildew, odor, decay, termite, and radon control strategies. Another useful feature are checklist chapter summaries covering major design considerations for each foundation type--basement, crawl space, and slab-on-grade. These checklist summaries are useful during design and construction inspection. The information in this handbook is drawn heavily from the first foundation handbook from the DOE/ORNL Building Envelope Systems and Materials Program, the Building Foundation Design Handbook (Labs et al., 1988), which is an extensive technical reference manual. This book presents what to do in foundation design'' in an inviting, concise format. This handbook is intended to serve the needs of active home builders; however, the information is pertinent to anyone involved in foundation design and construction decisions including homeowners, architects, and engineers. 17 refs., 49 figs., 18 tabs.

  16. Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment.

    PubMed

    Li, Qiang; Chen, Min; Liu, Hongmin; Yang, Liqun; Yang, Guiying

    2012-12-01

    The aim of this study was to investigate the pathological changes in a rat model of Alzheimer's disease (AD) and the effect of donepezil hydrochloride (HCl) treatment. The rat model of AD was established by the bilateral injection of amyloid β₁₋₄₀ (Aβ₁₋₄₀) into the hippocampus. Changes in spatial learning and memory functions were examined using the Morris water maze test and changes in catalase (CAT) and glutathione peroxidase (GSH-Px) activities were determined using chemical colorimetry. Moreover, the changes in acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) expression were analyzed using immunohistochemical staining. The mRNA expression levels of the amyloid precursor protein (APP) and β-secreted enzyme 1 (BACE1) were evaluated using RT-PCR. The effects of donepezil HCl on the aforementioned indices were also observed. The rat memories of the platform quadrants in the blank, sham and donepezil HCl groups were improved compared with those of the rats in the model group. The ratio of swim distance in the fourth platform quadrant (l₄) to the total swim distance (l total) for the model group rats (l₄/l total) was significantly decreased compared with that for the blank and sham group rats. Following donepezil HCl treatment, the ratio of l₄/l total significantly increased. AD modeling caused a significant decrease in the CAT and GSH-Px activities in the brain tissues of the rats. The CAT and GSH-Px activities in the AD model rats significantly increased following donepezil HCl treatment. Moreover, donepezil HCl treatment significantly decreased the AChE, APP and BACE1 mRNA expression levels and increased the ChAT expression levels. Therefore, donepezil HCl was able to significantly decrease learning and memory damage in a rat model of AD.

  17. Erosion of a-C:H films under interaction with nitrous oxide afterglow discharge

    NASA Astrophysics Data System (ADS)

    Zalavutdinov, R. Kh.; Gorodetsky, A. E.; Bukhovets, V. L.; Zakharov, A. P.; Mazul, I. V.

    2009-06-01

    Hydrocarbon film removal using chemically active oxygen formed in a direct current glow discharge with a hollow cathode in nitrous oxide was investigated. In the afterglow region sufficiently fast removal of a-C:H films about 500 nm thick during about 8 h was achieved at N 2O pressure of 12 Pa and 370 K. The erosion rate in the afterglow region was directly proportional to the initial pressure and increased two orders of magnitude at temperature rising from 300 to 500 K. The products of a-C:H film plasmolysis were CO, CO 2, H 2O, and H 2. After removal of a-C:H films previously deposited on stainless steel, molybdenum or tungsten 3-30 nm thick oxide films were formed on the substrates. Reactions of oxygen ion neutralization and atomic oxygen recombination suppressed further oxidation of the materials.

  18. Cleft Palate Foundation

    MedlinePlus

    ... Spanish , and Mandarin ! Information on Cleft Lip and Palate Our booklets and factsheets address a variety of ... Bear. –Paige with her Cleftline™ teddy bear– Cleft Palate Foundation 1504 East Franklin Street, Suite 102 Chapel ...

  19. Prostate Cancer Foundation

    MedlinePlus

    ... Close About Us Our Story A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... Cancer Board of Directors Annual Report & Financials Our Leadership Leadership Team A Legacy of Leadership Featured Take ...

  20. Children's Brain Tumor Foundation

    MedlinePlus

    ... CBTF Justin's Hope Fund Grant Recipients Grants Children’s Brain Tumor Foundation, A non-profit organization, was founded ... and the long term outlook for children with brain and spinal cord tumors through research, support, education, ...

  1. Oral Cancer Foundation

    MedlinePlus

    ... Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering and save lives ... National Academy of Sciences (NAS) is a private, non-profit society of distinguished scholars. Established by an Act ...

  2. Scleroderma Research Foundation

    MedlinePlus

    ... Research Foundation in your estate planning guarantees your lifetime commitment to finding a cure will continue. Learn more The SRF: A Four Star Charity The SRF has achieved the highest possible ...

  3. National Fragile X Foundation

    MedlinePlus

    ... Anthology Advocacy National Fragile X Foundation Advocacy Day STAR: Local Advocacy Agenda and Accomplishments Community Events International ... Feeding and Fragile X Toilet Training the Older Child Oppositional or Merely Anxious? Public or Private? Managing ...

  4. Pulmonary Fibrosis Foundation

    MedlinePlus

    ... Belts! For PFF Spend an evening with the stars on Monday, February 27, 2017. MORE PFF Moved ... Patients The Pulmonary Fibrosis Foundation has a four-star rating from Charity Navigator and is a Better ...

  5. American Lyme Disease Foundation

    MedlinePlus

    ... Infectious Diseases, 35: 451-464, 2002) What is Lyme Disease? Lyme disease (LD) is an infection caused by ... mission with your own tax-deductible contribution. American Lyme Disease Foundation, Inc. PO Box 466 Lyme, CT 06371 ...

  6. A Foundation for Research

    ERIC Educational Resources Information Center

    Fowler, William A.

    1975-01-01

    Discusses the funding of scientific research by the National Science Foundation (NSF) during the past 25 years. Reviews in general terms the types of broad research accomplished through NSF funds in various fields of science. (MLH)

  7. National Hydrocephalus Foundation

    MedlinePlus

    ... with Hydrocephalus Fetal MRI Advancements Normal Pressure Hydrocephalus Communication and Development Therapy Eye Findings in Hydrocephalus News & Events Member Benefits & Services How to Join Make a Donation Website design by SDGi . © 2014 National Hydrocephalus Foundation. All rights ...

  8. National Pancreas Foundation

    MedlinePlus

    ... to NPF Contact Us Newsletter Sign Up Social Networking Button – Medium Search: Main menu Skip to primary ... 20814 1.866.726.2737 | Contact Us Social Networking Button – Medium © 2014 The National Pancreas Foundation | Health ...

  9. National Ataxia Foundation

    MedlinePlus

    ... Minnesota Walk, Stroll n’ Roll St. Louis Park, MN September 10 New England Walk n’ Roll Bristol, ... Ataxia Foundation • 2600 Fernbrook Lane Suite 119 • Minneapolis, MN 55447 • 763.553.0020 naf@ataxia.org | Site ...

  10. National Reye's Syndrome Foundation

    MedlinePlus

    ... Packages - Free! Talking to Tweens and Teens About Aspirin and Other Medications Join the Effort to Eradicate ... Foundation's LinkedIn profile Spread Awareness with the Kids & Aspirin Don't Mix car magnet ribbon. Get News & ...

  11. United Leukodystrophy Foundation

    MedlinePlus

    ... Benefit Drawing to … Read More » Research Grant Applications Now Being Solicited The United Leukodystrophy Foundation is soliciting grant applications to support … Read More » Dr. Matalon Wins ULF Service Award Congratulations to Dr. Reuben Matalon ...

  12. Intracellular activity of tedizolid phosphate and ACH-702 versus Mycobacterium tuberculosis infected macrophages

    PubMed Central

    2014-01-01

    Background Due to the emergency of multidrug-resistant strains of Mycobacterium tuberculosis, is necessary the evaluation of new compounds. Findings Tedizolid, a novel oxazolidinone, and ACH-702, a new isothiazoloquinolone, were tested against M. tuberculosis infected THP-1 macrophages. These two compounds significantly decreased the number of intracellular mycobacteria at 0.25X, 1X, 4X and 16X the MIC value. The drugs were tested either in nanoparticules or in free solution. Conclusion Tedizolid and ACH-702 have a good intracellular killing activity comparable to that of rifampin or moxifloxacin. PMID:24708819

  13. nAChR agonist-induced cognition enhancement: integration of cognitive and neuronal mechanisms.

    PubMed

    Sarter, Martin; Parikh, Vinay; Howe, William M

    2009-10-01

    The identification and characterization of drugs for the treatment of cognitive disorders has been hampered by the absence of comprehensive hypotheses. Such hypotheses consist of (a) a precisely defined cognitive operation that fundamentally underlies a range of cognitive abilities and capacities and, if impaired, contributes to the manifestation of diverse cognitive symptoms; (b) defined neuronal mechanisms proposed to mediate the cognitive operation of interest; (c) evidence indicating that the putative cognition enhancer facilitates these neuronal mechanisms; (d) and evidence indicating that the cognition enhancer facilitates cognitive performance by modulating these underlying neuronal mechanisms. The evidence on the neuronal and attentional effects of nAChR agonists, specifically agonists selective for alpha4beta2* nAChRs, has begun to support such a hypothesis. nAChR agonists facilitate the detection of signals by augmenting the transient increases in prefrontal cholinergic activity that are necessary for a signal to gain control over behavior in attentional contexts. The prefrontal microcircuitry mediating these effects include alpha4beta2* nAChRs situated on the terminals of thalamic inputs and the glutamatergic stimulation of cholinergic terminals via ionotropic glutamate receptors. Collectively, this evidence forms the basis for hypothesis-guided development and characterization of cognition enhancers.

  14. Genome Sequence of the Mycorrhiza Helper Bacterium Streptomyces sp. Strain AcH 505.

    PubMed

    Tarkka, M T; Feldhahn, L; Buscot, F; Wubet, T

    2015-04-02

    A draft genome sequence of Streptomyces sp. strain AcH 505 is presented here. The genome encodes 22 secondary metabolite gene clusters and a large arsenal of secreted proteins, and their comparative and functional analyses will help to advance our knowledge of symbiotic interactions and fungal and plant biomass degradation.

  15. Genome Sequence of the Mycorrhiza Helper Bacterium Streptomyces sp. Strain AcH 505

    PubMed Central

    Feldhahn, L.; Buscot, F.; Wubet, T.

    2015-01-01

    A draft genome sequence of Streptomyces sp. strain AcH 505 is presented here. The genome encodes 22 secondary metabolite gene clusters and a large arsenal of secreted proteins, and their comparative and functional analyses will help to advance our knowledge of symbiotic interactions and fungal and plant biomass degradation. PMID:25838498

  16. Carbonaceous dust in interstellar shock waves: hydrogenated amorphous carbon (a-C:H) vs. graphite

    NASA Astrophysics Data System (ADS)

    Serra Díaz-Cano, L.; Jones, A. P.

    2008-12-01

    Context: Observations of regions of the interstellar medium affected by shock waves indicate gas phase abundances of carbon that are close to solar. In quiescent regions less than half of the carbon is in the gas phase. Aims: We propose that hydrogenated amorphous carbon (a-C:H), in its many guises, is the most probable form of carbonaceous grain material in the interstellar medium and study its erosion in shock waves. Methods: We have used the physical properties typical of a-C:H materials, rather than graphite/amorphous carbon, to study a-C:H erosion during ion irradiation and fragmentation in grain-grain collisions. Using SRIM we study material-, surface- and size-dependent sputtering effects and introduce these effects into a shock model. Results: We find significantly greater destruction for a-C:H, than for graphite, a result that brings the models into better agreement with existing observations of shocked regions of the ISM. Carbon grain erosion in shock waves therefore appears to be much more efficient than predicted by existing models. Conclusions: Interstellar hydrogenated amorphous carbon dust is, apparently, rather easily destroyed in shocks and must therefore be more rapidly re-cycled and re-formed during its journey through the interstellar medium than previously-thought.

  17. Draft Genome Sequence of Aldehyde-Degrading Strain Halomonas axialensis ACH-L-8

    PubMed Central

    Ye, Jun; Ren, Chong; Shan, Xiexie

    2016-01-01

    Halomonas axialensis ACH-L-8, a deep-sea strain isolated from the South China Sea, has the ability to degrade aldehydes. Here, we present an annotated draft genome sequence of this species, which could provide fundamental molecular information on the aldehydes-degrading mechanism. PMID:27081145

  18. Molecular recognition of thiaclopride by Aplysia californica AChBP: new insights from a computational investigation.

    PubMed

    Alamiddine, Zakaria; Selvam, Balaji; Cerón-Carrasco, José P; Mathé-Allainmat, Monique; Lebreton, Jacques; Thany, Steeve H; Laurent, Adèle D; Graton, Jérôme; Le Questel, Jean-Yves

    2015-12-01

    The binding of thiaclopride (THI), a neonicotinoid insecticide, with Aplysia californica acetylcholine binding protein (Ac-AChBP), the surrogate of the extracellular domain of insects nicotinic acetylcholine receptors, has been studied with a QM/QM' hybrid methodology using the ONIOM approach (M06-2X/6-311G(d):PM6). The contributions of Ac-AChBP key residues for THI binding are accurately quantified from a structural and energetic point of view. The importance of water mediated hydrogen-bond (H-bond) interactions involving two water molecules and Tyr55 and Ser189 residues in the vicinity of the THI nitrile group, is specially highlighted. A larger stabilization energy is obtained with the THI-Ac-AChBP complex compared to imidacloprid (IMI), the forerunner of neonicotinoid insecticides. Pairwise interaction energy calculations rationalize this result with, in particular, a significantly more important contribution of the pivotal aromatic residues Trp147 and Tyr188 with THI through CH···π/CH···O and π-π stacking interactions, respectively. These trends are confirmed through a complementary non-covalent interaction (NCI) analysis of selected THI-Ac-AChBP amino acid pairs. PMID:26589615

  19. 31 CFR 363.41 - What happens if an ACH payment is returned to Public Debt?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... returned to Public Debt? 363.41 Section 363.41 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT... TreasuryDirect § 363.41 What happens if an ACH payment is returned to Public Debt? We will notify...

  20. 31 CFR 363.41 - What happens if an ACH payment is returned to Public Debt?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... returned to Public Debt? 363.41 Section 363.41 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT... TreasuryDirect § 363.41 What happens if an ACH payment is returned to Public Debt? We will notify...

  1. 31 CFR 363.41 - What happens if an ACH payment is returned to Public Debt?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... returned to Public Debt? 363.41 Section 363.41 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT... TreasuryDirect § 363.41 What happens if an ACH payment is returned to Public Debt? We will notify...

  2. 31 CFR 363.41 - What happens if an ACH payment is returned to Public Debt?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... returned to Public Debt? 363.41 Section 363.41 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FISCAL SERVICE, DEPARTMENT OF THE TREASURY BUREAU OF THE PUBLIC DEBT... TreasuryDirect § 363.41 What happens if an ACH payment is returned to Public Debt? We will notify...

  3. Draft Genome Sequence of Aldehyde-Degrading Strain Halomonas axialensis ACH-L-8.

    PubMed

    Ye, Jun; Ren, Chong; Shan, Xiexie; Zeng, Runying

    2016-01-01

    Halomonas axialensisACH-L-8, a deep-sea strain isolated from the South China Sea, has the ability to degrade aldehydes. Here, we present an annotated draft genome sequence of this species, which could provide fundamental molecular information on the aldehydes-degrading mechanism.

  4. Non-neuronal release of ACh plays a key role in secretory response to luminal propionate in rat colon.

    PubMed

    Yajima, Takaji; Inoue, Ryo; Matsumoto, Megumi; Yajima, Masako

    2011-02-15

    Colonic chloride secretion is induced by chemical stimuli via the enteric nervous reflex. We have previously demonstrated that propionate stimulates chloride secretion via sensory and cholinergic systems of the mucosa in rat distal colon. In this study, we demonstrate non-neuronal release of ACh in the secretory response to propionate using an Ussing chamber. Mucosa preparations from the colon, not including the myenteric and submucosal plexuses, were used. Luminal addition of propionate and serosal addition of ACh caused biphasic changes in short-circuit current (Isc). TTX (1 μm) had no effects, while atropine (10 μm) significantly inhibited the Isc response to propionate and abolished that to ACh. In response to luminal propionate stimulation, ACh was released into the serosal fluid. A linear relationship was observed between the maximal increase in Isc and the amounts of ACh released 5 min after propionate stimulation. This ACh release induced by propionate was not affected by atropine and bumetanide, although both drugs significantly reduced the Isc responses to propionate. Luminal addition of 3-chloropropionate, an inactive analogue of propionate, abolished both ACh release and Isc response produced by propionate. RT-PCR analysis indicated that isolated crypt cells from the distal colon expressed an enzyme of ACh synthesis (ChAT) and transporters of organic cation (OCTs), but not neuronal CHT1 and VAChT. The isolated crypt cells contained comparable amounts of ACh to the residual muscle tissues including nerve plexuses. In conclusion, the non-neuronal release of ACh from colonocytes coupled with propionate stimulation plays a key role in chloride secretion, via the paracrine action of ACh on muscarinic receptors of colonocytes.

  5. Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: discovery of quinoxaline-based hybrid compounds with AChE, H₃R and BACE 1 inhibitory activities.

    PubMed

    Huang, Wenhai; Tang, Li; Shi, Ying; Huang, Shufang; Xu, Lei; Sheng, Rong; Wu, Peng; Li, Jia; Zhou, Naiming; Hu, Yongzhou

    2011-12-01

    A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H(3)R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H(3)R/AChE/BACE 1 (H(3)R antagonism, IC(50)=280.0 ± 98.0 nM; H(3)R inverse agonism, IC(50)=189.3 ± 95.7 nM; AChE, IC(50)=483 ± 5 nM; BACE 1, 46.64±2.55% inhibitory rate at 20 μM) and high selectivity over H(1)R/H(2)R/H(4)R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes.

  6. Thermodynamics: Frontiers and Foundations.

    SciTech Connect

    JEFFERY,; LEWINS, D.

    2009-07-27

    Version 00 Dr. J.D. Lewins has now released the following new book for free distribution: Thermodynamics: Frontiers and Foundations, Preface by Sir Alan Cottrell Introduction 1. Four-Square Foundations: The Laws of Thermodynamics 2. Maximum Entropy and Minimum Energy: The Master Functions and Equations 3. Ideal Gases and their Applications 4. Real Fluids and Some Applications 5. Van der Waals: A Model for Real Fluids 6. Surface Tension: Bubbles and Drops 7. Inert and Reactive Mixtures; An introduction to Chemical Thermodynamics 8. Radiation Thermodynamics: Solar Power Potential 9. Outposts of the Empire 10. A Glimpse into Statistical Thermodynamics Envoi

  7. Thermodynamics: Frontiers and Foundations.

    2009-07-27

    Version 00 Dr. J.D. Lewins has now released the following new book for free distribution: Thermodynamics: Frontiers and Foundations, Preface by Sir Alan Cottrell Introduction 1. Four-Square Foundations: The Laws of Thermodynamics 2. Maximum Entropy and Minimum Energy: The Master Functions and Equations 3. Ideal Gases and their Applications 4. Real Fluids and Some Applications 5. Van der Waals: A Model for Real Fluids 6. Surface Tension: Bubbles and Drops 7. Inert and Reactive Mixtures;more » An introduction to Chemical Thermodynamics 8. Radiation Thermodynamics: Solar Power Potential 9. Outposts of the Empire 10. A Glimpse into Statistical Thermodynamics Envoi« less

  8. Acetylcholinesterase-Fc Fusion Protein (AChE-Fc): A Novel Potential Organophosphate Bioscavenger with Extended Plasma Half-Life.

    PubMed

    Noy-Porat, Tal; Cohen, Ofer; Ehrlich, Sharon; Epstein, Eyal; Alcalay, Ron; Mazor, Ohad

    2015-08-19

    Acetylcholinesterase (AChE) is the physiological target of organophosphate nerve agent compounds. Currently, the development of a formulation for prophylactic administration of cholinesterases as bioscavengers in established risk situations of exposure to nerve agents is the incentive for many efforts. While cholinesterase bioscavengers were found to be highly effective in conferring protection against nerve agent exposure in animal models, their therapeutic use is complicated by short circulatory residence time. To create a bioscavenger with prolonged plasma half-life, compatible with biotechnological production and purification, a chimeric recombinant molecule of HuAChE coupled to the Fc region of human IgG1 was designed. The novel fusion protein, expressed in cultured cells under optimized conditions, maintains its full enzymatic activity, at levels similar to those of the recombinant AChE enzyme. Thus, this novel fusion product retained its binding affinity toward BW284c5 and propidium, and its bioscavenging reactivity toward the organophosphate-AChE inhibitors sarin and VX. Furthermore, when administered to mice, AChE-Fc exhibits exceptional circulatory residence longevity (MRT of 6000 min), superior to any other known cholinesterase-based recombinant bioscavengers. Owing to its optimized pharmacokinetic performance, high reactivity toward nerve agents, and ease of production, AChE-Fc emerges as a promising next-generation organophosphate bioscavenger.

  9. Activation of nicotinic ACh receptors with α4 subunits induces adenosine release at the rat carotid body

    PubMed Central

    Conde, Sílvia V; Monteiro, Emília C

    2006-01-01

    The effect of ACh on the release of adenosine was studied in rat whole carotid bodies, and the nicotinic ACh receptors involved in the stimulation of this release were characterized. ACh and nicotinic ACh receptor agonists, cytisine, DMPP and nicotine, caused a concentration-dependent increase in adenosine production during normoxia, with nicotine being more potent and efficient in stimulating adenosine release from rat CB than cytisine and DMPP. D-Tubocurarine, mecamylamine, DHβE and α-bungarotoxin, nicotinic ACh receptor antagonists, caused a concentration-dependent reduction in the release of adenosine evoked by hypoxia. The rank order of potency for nicotinic ACh receptor antagonists that inhibit adenosine release was DHβE>mecamylamine>D-tubocurarine>α-bungarotoxin. The effect of the endogenous agonist, ACh, which was mimicked by nicotine, was antagonized by DHβE, a selective nicotinic receptor antagonist. The ecto-5′-nucleotidase inhibitor AOPCP produces a 72% inhibition in the release of adenosine from CB evoked by nicotine. Taken together, these data indicate that ACh induced the production of adenosine, mainly from extracellular ATP catabolism at the CB through a mechanism that involves the activation of nicotinic receptors with α4 and β2 receptor subunits. PMID:16444287

  10. The Foundation Directory, Edition 4.

    ERIC Educational Resources Information Center

    Lewis, Marianna O., Ed.; Bowers, Patricia, Ed.

    The fourth edition of "The Foundation Directory" lists and describes 5,454 foundations and surveys their grants. The directory was prepared from foundation reports and government records. The foundations listed either have assets of $500.00 or made grants totally at least $25,000.00 in the year of record. Education is the leading beneficiary of…

  11. Cultivating Foundation Support for Education.

    ERIC Educational Resources Information Center

    Murphy, Mary Kay, Ed.

    The process of acquiring financial support from private foundations is discussed in 26 essays, divided into five categories (Targeting the Foundation Market; Getting Started: Tools of the Trade; The Process of Foundation Fund Raising; The Grant Maker's Perspective; and Focused Programs and Foundation Support). A prologue, "Ethics and Foundation…

  12. The Broad Foundations, 2008

    ERIC Educational Resources Information Center

    Broad Foundation, 2008

    2008-01-01

    This 2008 foundation report provides an opportunity to look back and ahead as the organization reviews what has been accomplished and identifies challenges to be tackled in the future in the areas of education, scientific and medical research, and the arts. Grant making from the perspective of grantees is presented in each area. [This document was…

  13. Foundation for the Future.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC. Directorate for Education and Human Resources.

    This document describes some of the many programs sponsored by the National Science Foundation in its efforts to continue to promote systemic science and mathematics education reform. Brief descriptions of the following programs are included: (1) Interactive Math Program Restructures 9-12 Math Education; (2) Algebra I Project Sparks Citywide…

  14. The Broad Foundations, 2006

    ERIC Educational Resources Information Center

    Broad Foundation, 2006

    2006-01-01

    The mission of the Broad Foundations is to transform K-12 urban public education through better governance, management, labor relations and competition; make significant contributions to advance major scientific and medical research; foster public appreciation of contemporary art by increasing access for audiences worldwide; and lead and…

  15. Immune Deficiency Foundation

    MedlinePlus

    ... for IDF Join our nationwide network of volunteers Resources For Patients & Families Peer Support Speak with someone who understands Locate a Physician ... secure Legacy Giving Establish your personal legacy and support IDF 'Immune Deficiency Foundation Remembers' Plaque Pay tribute to ... Educational Resources Find a wealth of IDF educational publications and ...

  16. Parkinson's Disease Foundation

    MedlinePlus

    ... PDF®), a division of the Parkinson's Foundation, seeks research proposals for emerging ideas to help solve, treat and end the disease. PDF investments of $2.7 million are part of its comprehensive strategy to mobilize ... Initiatives Research We Fund Results Apply ...

  17. Foundations of Distance Education.

    ERIC Educational Resources Information Center

    Morabito, Margaret Gorts

    The foundations, development, and delivery of distance education were examined through a literature review and first-hand experience in administration and teaching in an international online school. The evolution of distance education was traced from the 1800s, when it was a print-based method of instruction conducted at a distance, through the…

  18. α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells.

    PubMed

    Sun, Haiji; Ma, Xiaoli

    2015-09-01

    Cigarette smoking is the most important risk factor in the development of human lung cancer. Nicotine, the major component in tobacco, not only contributes to carcinogenesis but also promotes tumor metastasis. By binding to nicotinic acetylcholine receptors (nAChRs), nicotine induces the proliferation and migration of non-small cell lung cancer. Recently studies have indicated that α5-nAChR is highly associated with lung cancer risk and nicotine dependence. Nevertheless, it is unclear whether nicotine promotes the migration and invasion through activation of α5-nAChR in lung cancer. In the present study, A549 cell was exposed to 1μN nicotine for 8, 24 or 48h. Wound-healing assay and transwell assay were used to evaluate the capability of A549 cell migration and cell invasion, respectively. Silencing of α5-nAChR was done by siRNA. Western blotting and PCR were used to detect α5-nAChR expression. Nicotine can induce activation of α5-nAChR in association with increased migration and invasion of human lung cancer A549 cell. Treatment of cells with α5-nAChR specific siRNA blocks nicotine-stimulated activation of α5-nAChR and suppresses A549 cell migration and invasion. Reduction of α5-nAChR resulted in upregulation of E-cadherin, consistent with E-cadherin being inhibitive of cancer cell invasion. These findings suggest that nicotine-induced migration and invasion may occur in a mechanism through activation of α5-nAChR, which can contribute to metastasis or development of human lung cancer.

  19. Deposition of a-C:H films on a nanotrench pattern by bipolar PBII&D

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Nakahara, Yuya; Nagato, Keisuke; Choi, Junho

    2016-06-01

    In this study, hydrogenated amorphous carbon (a-C:H) films were deposited on a nanotrench pattern (300 nm pitch, aspect ratio: 2.0) by bipolar-type plasma based ion implantation and deposition technique (bipolar PBII&D), and the effects of bipolar pulse on the film properties were investigated. Moreover, the behaviour of ions and radicals surrounding the nanotrench was analyzed to clarify the coating mechanism and properties of the a-C:H films on the nanotrench. Further, thermal nanoimprint lithography was carried out using the nanotrench pattern coated with a-C:H films as the mold, and the mold release properties were evaluated. All nanotrench surfaces were successfully coated with the a-C:H films, but the film thickness on the top, sidewall, and bottom surfaces of the trench were not uniform. The surface roughness of the a-C:H films was found to decrease at a higher positive voltage; this happens due to the higher electron temperature around the nanotrench because of the surface migration of plasma particles arrived on the trench. The effects of the negative voltage on the behaviour of ions and radicals near the sidewall of the nanotrench are quite similar to those near the microtrench reported previously (Park et al 2014 J. Phys. D: Appl. Phys. 47 335306). However, the positive pulse voltage was also found to affect the behaviour of ions and radicals near the sidewall surface. The incident angles of ions on the sidewall surface increased with the positive pulse voltage because the energy of incoming ions on the trench decreases with increasing positive voltage. Moreover, the incident ion flux on the sidewall is affected by the positive voltage history. Further, the radical flux decreases with increasing positive voltage. It can be concluded that a higher positive voltage at a lower negative voltage condition is good to obtain better film properties and higher film thickness on the sidewall surface. Pattern transfer properties for the nanoimprint formed by

  20. Muscle aches

    MedlinePlus

    ... and fibromyalgia often respond well to massage. Gentle stretching exercises after a long rest period are also ... to try. A physical therapist can teach you stretching, toning, and aerobic exercises to help you feel ...

  1. Can hydroxylamine be a more potent nucleophile for the reactivation of tabun-inhibited AChE than prototype oxime drugs? An answer derived from quantum chemical and steered molecular dynamics studies.

    PubMed

    Lo, Rabindranath; Ganguly, Bishwajit

    2014-07-29

    Organophosphorus nerve agents are highly toxic compounds which strongly inhibit acetylcholinesterase (AChE) in the blood and in the central nervous system (CNS). Tabun is one of the highly toxic organophosphorus (OP) compounds and is resistant to many oxime drugs formulated for the reactivation of AChE. The reactivation mechanism of tabun-conjugated AChE with various drugs has been examined with density functional theory and ab initio quantum chemical calculations. The presence of a lone-pair located on the amidic group resists the nucleophilic attack at the phosphorus center of the tabun-conjugated AChE. We have shown that the newly designed drug candidate N-(pyridin-2-yl)hydroxylamine, at the MP2/6-31+G*//M05-2X/6-31G* level in the aqueous phase with the polarizable continuum solvation model (PCM), is more effective in reactivating the tabun-conjugated AChE than typical oxime drugs. The rate determining activation barrier with N-(pyridin-2-yl)hydroxylamine was found to be ∼1.7 kcal mol(-1), which is 7.2 kcal mol(-1) lower than the charged oxime trimedoxime (one of the most efficient reactivators in tabun poisonings). The greater nucleophilicity index (ω(-)) and higher CHelpG charge of pyridinylhydroxylamine compared to TMB4 support this observation. Furthermore, we have also examined the reactivation process of tabun-inhibited AChE with some other bis-quaternary oxime drug candidates such as methoxime (MMB4) and obidoxime. The docking analysis suggests that charged bis-quaternary pyridinium oximes have greater binding affinity inside the active-site gorge of AChE compared to the neutral pyridinylhydroxylamine. The peripheral ligand attached to the neutral pyridinylhydroxylamine enhanced the binding with the aromatic residues in the active-site gorge of AChE through effective π-π interactions. Steered molecular dynamics (SMD) simulations have also been performed with the charged oxime (TMB4) and the neutral hydroxylamine. From protein-drug interaction

  2. Microdemographic Determinants of Population Recovery among the Northern Aché.

    PubMed

    Baker, Jack D; Hill, Kim; Hurtado, A Magdalena; Alcantara, Adelamar; Hunsinger, Eddie; Sprague, Webb

    2015-01-01

    A pattern of population crash and rapid recovery is a common feature of the pacification and settlement experience of the indigenous peoples of tropical South America. Despite the obvious importance of these events to the demographic and anthropological sciences as a whole, as well as their significant practical implications, little is known about the microdemographic determinants of these paired phenomena. Using methods of asymptotic and stochastic demographic analysis, we reconstructed the microdemographic drivers of this history among one indigenous population: the Northern Aché of eastern Paraguay. This article explores the implications of these relationships for understanding the overall demographic turnaround observed within similar groups, as well as for the future trajectory of the Northern Aché in particular.

  3. Sound localisation ability of soldiers wearing infantry ACH and PASGT helmets.

    PubMed

    Scharine, Angelique A; Binseel, Mary S; Mermagen, Timothy; Letowski, Tomasz R

    2014-01-01

    Helmets provide soldiers with ballistic and fragmentation protection but impair auditory spatial processing. Missed auditory information can be fatal for a soldier; therefore, helmet design requires compromise between protection and optimal acoustics. Twelve soldiers localised two sound signals presented from six azimuth angles and three levels of elevation presented at two intensity levels and with three background noises. Each participant completed the task while wearing no helmet and with two U.S. Army infantry helmets - the Personnel Armor System for Ground Troops (PASGT) helmet and the Advanced Combat Helmet (ACH). Results showed a significant effect of helmet type on the size of both azimuth and elevation error. The effects of level, background noise, azimuth and elevation were found to be significant. There was no effect of sound signal type. As hypothesised, localisation accuracy was greatest when soldiers did not wear helmet, followed by the ACH. Performance was worst with the PASGT helmet.

  4. Deposition of a-C:H films on UHMWPE substrate and its wear-resistance

    NASA Astrophysics Data System (ADS)

    Xie, Dong; Liu, Hengjun; Deng, Xingrui; Leng, Y. X.; Huang, Nan

    2009-10-01

    In prosthetic hip replacements, ultrahigh molecular weight polyethylene (UHMWPE) wear debris is identified as the main factor limiting the lifetime of the artificial joints. Especially UHMWPE debris from the joint can induce tissue reactions and bone resorption that may lead to the joint loosening. The diamond like carbon (DLC) film has attracted a great deal of interest in recent years mainly because of its excellent tribological property, biocompatibility and chemically inert property. In order to improve the wear-resistance of UHMWPE, a-C:H films were deposited on UHMWPE substrate by electron cyclotron resonance microwave plasma chemical vapor deposition (ECR-PECVD) technology. During deposition, the working gases were argon and acetylene, the microwave power was set to 800 W, the biased pulsed voltage was set to -200 V (frequency 15 kHz, duty ratio 20%), the pressure in vacuum chamber was set to 0.5 Pa, and the process time was 60 min. The films were analysed by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, nano-indentation, anti-scratch and wear test. The results showed that a typical amorphous hydrogenated carbon (a-C:H) film was successfully deposited on UHMWPE with thickness up to 2 μm. The nano-hardness of the UHMWPE coated with a-C:H films, measured at an applied load of 200 μN, was increased from 10 MPa (untreated UHMWPE) to 139 MPa. The wear test was carried out using a ball (Ø 6 mm, SiC) on disk tribometer with an applied load of 1 N for 10000 cycles, and the results showed a reduction of worn cross-sectional area from 193 μm 2 of untreated UHMWPE to 26 μm 2 of DLC coated sample. In addition the influence of argon/acetylene gas flow ratio on the growth of a-C:H films was studied.

  5. Mechanism of interaction of novel uncharged, centrally active reactivators with OP-hAChE conjugates.

    PubMed

    Radić, Zoran; Sit, Rakesh K; Garcia, Edzna; Zhang, Limin; Berend, Suzana; Kovarik, Zrinka; Amitai, Gabriel; Fokin, Valery V; Barry Sharpless, K; Taylor, Palmer

    2013-03-25

    A library of more than 200 novel uncharged oxime reactivators was used to select and refine lead reactivators of human acetylcholinesterase (hAChE) covalently conjugated with sarin, cyclosarin, VX, paraoxon and tabun. N-substituted 2-hydroxyiminoacetamido alkylamines were identified as best reactivators and reactivation kinetics of the lead oximes, RS41A and RS194B, were analyzed in detail. Compared to reference pyridinium reactivators, 2PAM and MMB4, molecular recognition of RS41A reflected in its Kox constant was compromised by an order of magnitude on average for different OP-hAChE conjugates, without significant differences in the first order maximal phosphorylation rate constant k(2). Systematic structural modifications of the RS41A lead resulted in several-fold improvement with reactivator, RS194B. Kinetic analysis indicated K(ox) reduction for RS194B as the main kinetic constant leading to efficient reactivation. Subtle structural modifications of RS194B were used to identify essential determinants for efficient reactivation. Computational molecular modeling of RS41A and RS194B interactions with VX inhibited hAChE, bound reversibly in Michaelis type complex and covalently in the pentacoordinate reaction intermediate suggests that the faster reactivation reaction is a consequence of a tighter RS194B interactions with hAChE peripheral site (PAS) residues, in particular with D74, resulting in lower interaction energies for formation of both the binding and reactivation states. Desirable in vitro reactivation properties of RS194B, when coupled with its in vivo pharmacokinetics and disposition in the body, reveal the potential of this oxime design as promising centrally and peripherally active antidotes for OP toxicity.

  6. Evidence for aging theories from the study of a hunter-gatherer people (Ache of Paraguay).

    PubMed

    Libertini, G

    2013-09-01

    In the late seventies, a small tribal population of Paraguay, the Ache, living under natural conditions, was studied. Data from this population turn out to be useful for considerations about evolutionary hypotheses on the aging phenomenon. 1) Ache show an age-related increasing mortality, which strongly limits the mean duration of life, as observed in other studies on mammal and bird species. 2) According to current theories on aging, in the wild very few or no individual reach old age and, so, aging cannot be directly influenced by natural selection. However, data from our population show that a significant proportion of the population reaches in the wild 60 and 70 years of age. 3) Data from Ache are also in agreement with the observation about an inverse correlation between extrinsic mortality and deaths due to the age-related increasing mortality. 4) For many gerontologists, the age-related decline of vital functions is a consequence of the gradual decline of cell turnover, genetically determined and regulated by the declining duplication capacities of stem cells. The current interpretation is that these restrictions are a general defense against the proliferation of any tumoral mass. However, among wild Ache cancer is virtually unknown in non-elderly subjects, and only among older individuals are there deaths attributable to oncological diseases. Moreover, fitness decline begins long before oncological diseases have fatal effects in significant numbers. This completely disproves the current hypothesis, because a supposed defense against a deadly disease cannot exterminate a population before the disease begins to kill. These data are consistent with similar data from other species studied under natural conditions, and they bring new arguments against the non-adaptive interpretation of aging and in support of the adaptive interpretation.

  7. Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay.

    PubMed

    Bribiescas, Richard G; Hill, Kim R

    2010-01-01

    Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age-related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age-associated variation in testosterone, it was hypothesized that Ache men would not show age-related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18-64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = -0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40-49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within-individual analyses of diurnal variation capture age-related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context.

  8. Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor

    PubMed Central

    Schrage, R; Seemann, WK; Klöckner, J; Dallanoce, C; Racké, K; Kostenis, E; De Amici, M; Holzgrabe, U; Mohr, K

    2013-01-01

    Background and Purpose Artificial agonists may have higher efficacy for receptor activation than the physiological agonist. Until now, such ‘superagonism’ has rarely been reported for GPCRs. Iperoxo is an extremely potent muscarinic receptor agonist. We hypothesized that iperoxo is a ‘superagonist’. Experimental Approach Signalling of iperoxo and newly synthesized structural analogues was compared with that of ACh at label-free M2 muscarinic receptors applying whole cell dynamic mass redistribution, measurement of G-protein activation, evaluation of cell surface agonist binding and computation of operational efficacies. Key Results In CHO-hM2 cells, iperoxo significantly exceeds ACh in Gi/Gs signalling competence. In the orthosteric loss-of-function mutant M2-Y1043.33A, the maximum effect of iperoxo is hardly compromised in contrast to ACh. ‘Superagonism’ is preserved in the physiological cellular context of MRC-5 human lung fibroblasts. Structure–signalling relationships including iperoxo derivatives with either modified positively charged head group or altered tail suggest that ‘superagonism’ of iperoxo is mechanistically based on parallel activation of the receptor protein via two orthosteric interaction points. Conclusion and Implications Supraphysiological agonist efficacy at muscarinic M2 ACh receptors is demonstrated for the first time. In addition, a possible underlying molecular mechanism of GPCR ‘superagonism’ is provided. We suggest that iperoxo-like orthosteric GPCR activation is a new avenue towards a novel class of receptor activators. Linked Article This article is commented on by Langmead and Christopoulos, pp. 353–356 of this issue. To view this commentary visit http://dx.doi.org/10.1111/bph.12142 PMID:23062057

  9. Foundations of logic programming

    SciTech Connect

    Lloyd, J.W.

    1987-01-01

    This is the second edition of the first book to give an account of the mathematical foundations of Logic Programming. Its purpose is to collect the basic theoretical results of Logic Programming, which have previously only been available in widely scattered research papers. In addition to presenting the technical results, the book also contains many illustrative examples. Many of the examples and problems are part of the folklore of Logic Programming and are not easily obtainable elsewhere.

  10. CONVEYOR FOUNDATIONS CALCULATION

    SciTech Connect

    S. Romanos

    1995-03-10

    The purpose of these calculations is to design foundations for all conveyor supports for the surface conveyors that transport the muck resulting from the TBM operation, from the belt storage to the muck stockpile. These conveyors consist of: (1) Conveyor W-TO3, from the belt storage, at the starter tunnel, to the transfer tower. (2) Conveyor W-SO1, from the transfer tower to the material stacker, at the muck stockpile.

  11. The stabilization of Au NP-AChE nanocomposites by biosilica encapsulation for the development of a thiocholine biosensor.

    PubMed

    Buiculescu, Raluca; Chaniotakis, Nikos A

    2012-08-01

    We report on the construction of an amperometric biosensor based on the immobilization of the enzyme acetylcholinesterase (AChE) onto gold nanoparticles (Au NPs). The active enzyme is covalently bound directly onto the surface of the Au NPs via a thiol bond. This immobilization provides increased stability and high electron-transfer between the colloidal Au NPs, the catalyst and the transducer surface. To further increase the biosensor stability by protecting the enzyme from denaturation and protease attack, a layer of biosilica was grown around the Au NP enzyme nanocomposite. All steps, i.e., the conjugation of the enzyme to the gold nanoparticles and the encapsulation into biosilica, are monitored and confirmed by ATR-FT-IR spectroscopy. The stabilizing effect of the entrapment was evaluated amperometrically, while the operation of the biosensor was monitored over a period of 4 months. The initial sensitivity of the biosensor was calculated to be 27.58 nA mM(-1) with a linear response to the concentration of the substrate in the range from 0.04 to 0.4 mM. It is thus shown that the biosilica nanocomposites doped with Au NPs-AChE conjugates create a system that provides both signal mediation and significant enzyme stabilization over the existing AChE biosensor. The biosensor had retained all its activity at the end of the 4 months, compared with the normal AChE biosensor whose activity reached 50% after only 42 days of operation.

  12. Wronski's Foundations of Mathematics.

    PubMed

    Wagner, Roi

    2016-09-01

    Argument This paper reconstructs Wronski's philosophical foundations of mathematics. It uses his critique of Lagrange's algebraic analysis as a vignette to introduce the problems that he raised, and argues that these problems have not been properly appreciated by his contemporaries and subsequent commentators. The paper goes on to reconstruct Wronski's mathematical law of creation and his notions of theory and techne, in order to put his objections to Lagrange in their philosophical context. Finally, Wronski's proof of his universal law (the expansion of a given function by any series of functions) is reviewed in terms of the above reconstruction. I argue that Wronski's philosophical approach poses an alternative to the views of his contemporary mainstream mathematicians, which brings up the contingency of their choices, and bridges the foundational concerns of early modernity with those of the twentieth-century foundations crisis. I also argue that Wronski's views may be useful to contemporary philosophy of mathematical practice, if they are read against their metaphysical grain. PMID:27573997

  13. Physicians and foundation hospitals.

    PubMed

    Cooper, John; Black, Carol

    2003-01-01

    Foundation NHS Trusts will be constituted in the same way as Mutual Societies, and local people and patients will be invited to become subscribers. Subscribers will elect a board of governors who will appoint the non-executive directors of the Trusts. Foundation Trusts will be outside the performance management system, but will be subject to a regulator and to inspection. Contracts with commissioners will be legally enforceable. Issues discussed in the article include: financial borrowing; whether competition is being reintroduced; poaching staff; fears of a two-tier health service; fragmentation of the NHS; the impact on research and teaching; and the impact on the current 'target culture'. Local communities and patient groups may welcome involvement with their local hospitals, but special interest groups could be a danger. Foundation Trusts may bring back some of the better features of NHS Trusts as originally conceived, and offer better opportunities for clinicians to influence local policies and priorities. Fears of yet another organisational change are an important issue. Only time will tell whether the outcome will justify the effort the changes will involve. PMID:14703035

  14. Wronski's Foundations of Mathematics.

    PubMed

    Wagner, Roi

    2016-09-01

    Argument This paper reconstructs Wronski's philosophical foundations of mathematics. It uses his critique of Lagrange's algebraic analysis as a vignette to introduce the problems that he raised, and argues that these problems have not been properly appreciated by his contemporaries and subsequent commentators. The paper goes on to reconstruct Wronski's mathematical law of creation and his notions of theory and techne, in order to put his objections to Lagrange in their philosophical context. Finally, Wronski's proof of his universal law (the expansion of a given function by any series of functions) is reviewed in terms of the above reconstruction. I argue that Wronski's philosophical approach poses an alternative to the views of his contemporary mainstream mathematicians, which brings up the contingency of their choices, and bridges the foundational concerns of early modernity with those of the twentieth-century foundations crisis. I also argue that Wronski's views may be useful to contemporary philosophy of mathematical practice, if they are read against their metaphysical grain.

  15. Foundations of chaotic mixing.

    PubMed

    Wiggins, Stephen; Ottino, Julio M

    2004-05-15

    The simplest mixing problem corresponds to the mixing of a fluid with itself; this case provides a foundation on which the subject rests. The objective here is to study mixing independently of the mechanisms used to create the motion and review elements of theory focusing mostly on mathematical foundations and minimal models. The flows under consideration will be of two types: two-dimensional (2D) 'blinking flows', or three-dimensional (3D) duct flows. Given that mixing in continuous 3D duct flows depends critically on cross-sectional mixing, and that many microfluidic applications involve continuous flows, we focus on the essential aspects of mixing in 2D flows, as they provide a foundation from which to base our understanding of more complex cases. The baker's transformation is taken as the centrepiece for describing the dynamical systems framework. In particular, a hierarchy of characterizations of mixing exist, Bernoulli --> mixing --> ergodic, ordered according to the quality of mixing (the strongest first). Most importantly for the design process, we show how the so-called linked twist maps function as a minimal picture of mixing, provide a mathematical structure for understanding the type of 2D flows that arise in many micromixers already built, and give conditions guaranteeing the best quality mixing. Extensions of these concepts lead to first-principle-based designs without resorting to lengthy computations.

  16. Expression of human AChR extracellular domain mutants with improved characteristics.

    PubMed

    Lazaridis, Konstantinos; Zisimopoulou, Paraskevi; Giastas, Petros; Bitzopoulou, Kalliopi; Evangelakou, Panagiota; Sideri, Anastasia; Tzartos, Socrates J

    2014-02-01

    The muscle nicotinic acetylcholine receptor (AChR) has a central role in neuromuscular transmission, and is the major target in the autoimmune disease myasthenia gravis (MG). We created mutants of the extracellular domains (ECDs) of the human α1, β1, δ and ε AChR subunits, whereby their Cys-loop was exchanged for that of the acetylcholine binding protein. The mutants were expressed in Pichia pastoris and had improved solubility resulting in 2- to 43-fold higher expression yields compared to the wild type. An additional mutant was created for the α1 ECD restoring its glycosylation site within the Cys-loop and its α-bungarotoxin binding ability. Furthermore, we constructed dimeric and pentameric concatamers of the mutant ECDs. All concatamers were successfully expressed as soluble secreted proteins, although the pentamers had about 10-fold lower expression than the dimers and were more susceptible to fragmentation. Initial crystallizations with the mutant ECDs were promising, and we reproducibly obtained crystals of the β1 ECD, diffracting at ~12 Å. Further optimization is underway to obtain crystals suitable for high resolution crystallography. The proteins described herein are useful tools in structural studies of the human muscle AChR and can be used in applications requiring high yields such as therapeutic adsorbents for MG autoantibodies. PMID:24246999

  17. The Role of nAChR and Calcium Signaling in Pancreatic Cancer Initiation and Progression

    PubMed Central

    Schaal, Courtney; Padmanabhan, Jaya; Chellappan, Srikumar

    2015-01-01

    Pancreatic cancer shows a strong correlation with smoking and the current therapeutic strategies have been relatively ineffective in improving the survival of patients. Efforts have been made over the past many years to understand the molecular events that drive the initiation and progression of pancreatic cancer, especially in the context of smoking. It has become clear that components of tobacco smoke not only initiate these cancers, especially pancreatic ductal adenocarcinomas (PDACs) through their mutagenic properties, but can also promote the growth and metastasis of these tumors by stimulating cell proliferation, angiogenesis, invasion and epithelial-mesenchymal transition. Studies in cell culture systems, animal models and human samples have shown that nicotinic acetylcholine receptor (nAChR) activation enhances these tumor-promoting events by channeling signaling through multiple pathways. In this context, signaling through calcium channels appear to facilitate pancreatic cancer growth by itself or downstream of nAChRs. This review article highlights the role of nAChR downstream signaling events and calcium signaling in the growth, metastasis as well as drug resistance of pancreatic cancer. PMID:26264026

  18. Selective activation of α7 nicotinic acetylcholine receptor (nAChRα7) inhibits muscular degeneration in mdx dystrophic mice.

    PubMed

    Leite, Paulo Emílio Correa; Gandía, Luís; de Pascual, Ricardo; Nanclares, Carmen; Colmena, Inés; Santos, Wilson C; Lagrota-Candido, Jussara; Quirico-Santos, Thereza

    2014-07-21

    Amount evidence indicates that α7 nicotinic acetylcholine receptor (nAChRα7) activation reduces production of inflammatory mediators. This work aimed to verify the influence of endogenous nAChRα7 activation on the regulation of full-blown muscular inflammation in mdx mouse with Duchenne muscular dystrophy. We used mdx mice with 3 weeks-old at the height myonecrosis, and C57 nAChRα7(+/+) wild-type and nAChRα7(-/-) knockout mice with muscular injury induced with 60µL 0.5% bupivacaine (bp) in the gastrocnemius muscle. Pharmacological treatment included selective nAChRα7 agonist PNU282987 (0.3mg/kg and 1.0mg/kg) and the antagonist methyllycaconitine (MLA at 1.0mg/kg) injected intraperitoneally for 7 days. Selective nAChRα7 activation of mdx mice with PNU282987 reduced circulating levels of lactate dehydrogenase (LDH, a marker of cell death by necrosis) and the area of perivascular inflammatory infiltrate, and production of inflammatory mediators TNFα and metalloprotease MMP-9 activity. Conversely, PNU282987 treatment increased MMP-2 activity, an indication of muscular tissue remodeling associated with regeneration, in both mdx mice and WTα7 mice with bp-induced muscular lesion. Treatment with PNU282987 had no effect on α7KO, and MLA abolished the nAChRα7 agonist-induced anti-inflammatory effect in both mdx and WT. In conclusion, nAChRα7 activation inhibits muscular inflammation and activates tissue remodeling by increasing muscular regeneration. These effects were not accompanied with fibrosis and/or deposition of non-functional collagen. The nAChRα7 activation may be considered as a potential target for pharmacological strategies to reduce inflammation and activate mechanisms of muscular regeneration. PMID:24833065

  19. The α3β4* nicotinic ACh receptor subtype mediates physical dependence to morphine: mouse and human studies

    PubMed Central

    Muldoon, P P; Jackson, K J; Perez, E; Harenza, J L; Molas, S; Rais, B; Anwar, H; Zaveri, N T; Maldonado, R; Maskos, U; McIntosh, J M; Dierssen, M; Miles, M F; Chen, X; De Biasi, M; Damaj, M I

    2014-01-01

    BACKGROUND AND PURPOSE Recent data have indicated that α3β4* neuronal nicotinic (n) ACh receptors may play a role in morphine dependence. Here we investigated if nACh receptors modulate morphine physical withdrawal. EXPERIMENTAL APPROACHES To assess the role of α3β4* nACh receptors in morphine withdrawal, we used a genetic correlation approach using publically available datasets within the GeneNetwork web resource, genetic knockout and pharmacological tools. Male and female European-American (n = 2772) and African-American (n = 1309) subjects from the Study of Addiction: Genetics and Environment dataset were assessed for possible associations of polymorphisms in the 15q25 gene cluster and opioid dependence. KEY RESULTS BXD recombinant mouse lines demonstrated an increased expression of α3, β4 and α5 nACh receptor mRNA in the forebrain and midbrain, which significantly correlated with increased defecation in mice undergoing morphine withdrawal. Mice overexpressing the gene cluster CHRNA5/A3/B4 exhibited increased somatic signs of withdrawal. Furthermore, α5 and β4 nACh receptor knockout mice expressed decreased somatic withdrawal signs compared with their wild-type counterparts. Moreover, selective α3β4* nACh receptor antagonists, α-conotoxin AuIB and AT-1001, attenuated somatic signs of morphine withdrawal in a dose-related manner. In addition, two human datasets revealed a protective role for variants in the CHRNA3 gene, which codes for the α3 nACh receptor subunit, in opioid dependence and withdrawal. In contrast, we found that the α4β2* nACh receptor subtype is not involved in morphine somatic withdrawal signs. CONCLUSION AND IMPLICATIONS Overall, our findings suggest an important role for the α3β4* nACh receptor subtype in morphine physical dependence. PMID:24750073

  20. Silencing A7-nAChR levels increases the sensitivity of gastric cancer cells to ixabepilone treatment.

    PubMed

    Tu, Chao-Chiang; Huang, Chien-Yu; Cheng, Wan-Li; Hung, Chin-Sheng; Chang, Yu-Jia; Wei, Po-Li

    2016-07-01

    Gastric cancer is an important health issue worldwide. Currently, improving the therapeutic efficacy of chemotherapy drugs is an important goal of cancer research. Alpha-7 nicotine acetylcholine receptor (A7-nAChR) is the key molecule that mediates gastric cancer progression, metastasis, and therapy responses; however, the role of A7-nAChR in the therapeutic efficacy of ixabepilone remains unclear. A7-nAChR expression was silenced by small interfering RNA (siRNA) technology. The cytotoxicity of ixabepilone was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and ixabepilone-induced apoptosis was analyzed by flow cytometry and annexin V/propidium iodide (PI) apoptotic assay. The expression patterns of anti-apoptotic proteins (AKT, phospho-AKT, Mcl-1, and Bcl-2) and pro-apoptotic proteins (Bad and Bax) were determined by western blot. Our study found that A7-nAChR knockdown (A7-nAChR-KD) AGS cells were more sensitive to ixabepilone administration than scrambled control AGS cells. We found that A7-nAChR knockdown enhanced ixabepilone-induced cell death as evidenced by the increased number of annexin V-positive (apoptotic) cells. After scrambled control and A7-nAChR-KD cells were treated with ixabepilone, we found that pAKT and AKT levels were significantly reduced in both groups of cells. The levels of Bcl-2 and the anti-apoptotic Mcl-1 isoform increased dramatically after ixabepilone treatment in scrambled control cells but not in A7-nAChR-KD cells. Bad and Bax levels did not change between the treatment group and vehicle group in both A7-nAChR-KD and scrambled control cells, whereas cleaved PARP levels dramatically increased in ixabepilone-treated A7-nAChR-KD cells. Our results demonstrated that knockdown of A7-nAChR enhanced the sensitivity of gastric cancer cells to ixabepilone administration. Thus, the A7-nAChR expression level in patients with gastric cancer may be a good indicator of ixabepilone sensitivity.

  1. Otilonium: a potent blocker of neuronal nicotinic ACh receptors in bovine chromaffin cells.

    PubMed Central

    Gandía, L.; Villarroya, M.; Lara, B.; Olmos, V.; Gilabert, J. A.; López, M. G.; Martínez-Sierra, R.; Borges, R.; García, A. G.

    1996-01-01

    1. Otilonium, a clinically useful spasmolytic, behaves as a potent blocker of neuronal nicotinic acetylcholine receptors (AChR) as well as a mild wide-spectrum Ca2+ channel blocker in bovine adrenal chromaffin cells. 2. 45Ca2+ uptake into chromaffin cells stimulated with high K+ (70 mM, 1 min) was blocked by otilonium with an IC50 of 7.6 microM. The drug inhibited the 45Ca2+ uptake stimulated by the nicotinic AChR agonist, dimethylphenylpiperazinium (DMPP) with a 79 fold higher potency (IC50 = 0.096 microM). 3. Whole-cell Ba2+ currents (IBa) through Ca2+ channels of voltage-clamped chromaffin cells were blocked by otilonium with an IC50 of 6.4 microM, very close to that of K(+)-evoked 45Ca2+ uptake. Blockade developed in 10-20 s, almost as a single step and was rapidly and almost fully reversible. 4. Whole-cell nicotinic AChR-mediated currents (250 ms pulses of 100 microM DMPP) applied at 30 s intervals were blocked by otilonium in a concentration-dependent manner, showing an IC50 of 0.36 microM. Blockade was induced in a step-wise manner. Wash out of otilonium allowed a slow recovery of the current, also in discrete steps. 5. In experiments with recordings in the same cells of whole-cell IDMPP, Na+ currents (INa) and Ca2+ currents (ICa), 1 microM otilonium blocked 87% IDMPP, 7% INa and 13% ICa. 6. Otilonium inhibited the K(+)-evoked catecholamine secretory response of superfused bovine chromaffin cells with an IC50 of 10 microM, very close to the IC50 for blockade of K(+)-induced 45Ca2+ uptake and IBa. 7. Otilonium inhibited the secretory responses induced by 10 s pulses of 50 microM DMPP with an IC50 of 7.4 nM. Hexamethonium blocked the DMPP-evoked responses with an IC50 of 29.8 microM, 4,000 fold higher than that of otilonium. 8. In conclusion, otilonium is a potent blocker of nicotinic AChR-mediated responses. The drugs also blocked various subtypes of neuronal voltage-dependent Ca2+ channels at a considerably lower potency. Na+ channels were unaffected by

  2. The dual-acting H3 receptor antagonist and AChE inhibitor UW-MD-71 dose-dependently enhances memory retrieval and reverses dizocilpine-induced memory impairment in rats.

    PubMed

    Khan, Nadia; Saad, Ali; Nurulain, Syed M; Darras, Fouad H; Decker, Michael; Sadek, Bassem

    2016-01-15

    Both the histamine H3 receptor (H3R) and acetylcholine esterase (AChE) are involved in the regulation of release and metabolism of acetylcholine and several other central neurotransmitters. Therefore, dual-active H3R antagonists and AChE inhibitors (AChEIs) have shown in several studies to hold promise to treat cognitive disorders like Alzheimer's disease (AD). The novel dual-acting H3R antagonist and AChEI 7-(3-(piperidin-1-yl)propoxy)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline (UW-MD-71) with excellent selectivity profiles over both the three other HRs as well as the AChE's isoenzyme butyrylcholinesterase (BChE) shows high and balanced in vitro affinities at both H3R and AChE with IC50 of 33.9nM and hH3R antagonism with Ki of 76.2nM, respectively. In the present study, the effects of UW-MD-71 (1.25-5mg/kg, i.p.) on acquisition, consolidation, and retrieval in a one-trial inhibitory avoidance task in male rats were investigated applying donepezil (DOZ) and pitolisant (PIT) as reference drugs. Furthermore, the effects of UW-MD-71 on memory deficits induced by the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (DIZ) were tested. Our results indicate that administration of UW-MD-71 before the test session dose-dependently increased performance and enhanced procognitive effect on retrieval. However neither pre- nor post-training acute systemic administration of UW-MD-71 facilitated acquisition or consolidation. More importantly, UW-MD-71 (2.5mg/kg, i.p.) ameliorated the DIZ-induced amnesic effects. Furthermore, the procognitive activity of UW-MD-71 in retrieval was completely reversed and partly abrogated in DIZ-induced amnesia when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL), but not with the CNS penetrant H1R antagonist pyrilamine (PYR). These results demonstrate the procognitive effects of UW-MD-71 in two in vivo memory models, and are to our knowledge the first demonstration in vivo that a potent dual

  3. Farm Foundation Annual Report, 2000.

    ERIC Educational Resources Information Center

    Farm Foundation, Oak Brook, IL.

    The Farm Foundation was established in 1933 as a private agency to help coordinate the work of other public and private groups and agencies to improve agriculture and rural life without taking political positions or supporting specific legislation. An operating rather than a grant-making foundation, the foundation develops national and regional…

  4. Students' Perceptions of Foundation Degrees

    ERIC Educational Resources Information Center

    Ooms, A.; Burke, L. M.; Marks-Maran, D. J.; Webb, M.; Cooper, D.

    2012-01-01

    In 2008 there were 87,339 people enrolled on foundation degrees (FDs) in the UK (Foundation Degree Forward, 2009), and educational institutions in the UK offered 1700 different foundation degrees in over 25 subjects, with nearly 900 more in development (Action on Access, 2010). In addition, student views are seen to be of importance, as…

  5. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

    PubMed

    Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

    2014-09-01

    Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity. PMID:24927388

  6. Biochemical effects of glyphosate based herbicide, Excel Mera 71 on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content on teleostean fishes.

    PubMed

    Samanta, Palas; Pal, Sandipan; Mukherjee, Aloke Kumar; Ghosh, Apurba Ratan

    2014-09-01

    Effects of glyphosate based herbicide, Excel Mera 71 at a dose of 17.20mg/l on enzyme activities of acetylcholinesterase (AChE), lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST) and protein content were measured in different tissues of two Indian air-breathing teleosts, Anabas testudineus (Bloch) and Heteropneustes fossilis (Bloch) during an exposure period of 30 days under laboratory condition. AChE activity was significantly increased in all the investigated tissues of both fish species and maximum elevation was observed in brain of H. fossilis, while spinal cord of A. testudineus showed minimum increment. Fishes showed significant increase LPO levels in all the tissues; highest was observed in gill of A. testudineus but lowest LPO level was observed in muscle of H. fossilis. CAT was also enhanced in both the fishes, while GST activity in liver diminished substantially and minimum was observed in liver of A. testudineus. Total protein content showed decreased value in all the tissues, maximum reduction was observed in liver and minimum in brain of A. testudineus and H. fossilis respectively. The results indicated that Excel Mera 71 caused serious alterations in the enzyme activities resulting into severe deterioration of fish health; so, AChE, LPO, CAT and GST can be used as suitable indicators of herbicidal toxicity.

  7. Sympathetic α₃β₂-nAChRs mediate cerebral neurogenic nitrergic vasodilation in the swine.

    PubMed

    Lee, Reggie Hui-Chao; Liu, Yi-Qing; Chen, Po-Yi; Liu, Chin-Hung; Chen, Mei-Fang; Lin, Hung-Wen; Kuo, Jon-Son; Premkumar, Louis S; Lee, Tony Jer-Fu

    2011-08-01

    The α(7)-nicotinic ACh receptor (α(7)-nAChR) on sympathetic neurons innervating basilar arteries of pigs crossed bred between Landrace and Yorkshire (LY) is known to mediate nicotine-induced, β-amyloid (Aβ)-sensitive nitrergic neurogenic vasodilation. Preliminary studies, however, demonstrated that nicotine-induced cerebral vasodilation in pigs crossbred among Landrace, Yorkshire, and Duroc (LYD) was insensitive to Aβ and α-bungarotoxin (α-BGTX). We investigated nAChR subtype on sympathetic neurons innervating LYD basilar arteries. Nicotine-induced relaxation of porcine isolated basilar arteries was examined by tissue bath myography, inward currents on nAChR-expressing oocytes by two-electrode voltage recording, and mRNA and protein expression in the superior cervical ganglion (SCG) and middle cervical ganglion (MCG) by reverse transcription PCR and Western blotting. Nicotine-induced basilar arterial relaxation was not affected by Aβ, α-BGTX, and α-conotoxin IMI (α(7)-nAChR antagonists), or α-conotoxin AuIB (α(3)β(4)-nAChR antagonist) but was inhibited by tropinone and tropane (α(3)-containing nAChR antagonists) and α-conotoxin MII (selective α(3)β(2)-nAChR antagonist). Nicotine-induced inward currents in α(3)β(2)-nAChR-expressing oocytes were inhibited by α-conotoxin MII but not by α-BGTX, Aβ, or α-conotoxin AuIB. mRNAs of α(3)-, α(7)-, β(2)-, and β(4)-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of α(3)-, β(2)-, and β(4)-subunits than that of α(7)-subunit. The Aβ-insensitive sympathetic α(3)β(2)-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from Aβ-sensitive α(7)-nAChR in basilar arteries of LY pigs may offer a partial explanation for different sensitivities of individuals to Aβ in causing diminished cerebral nitrergic vasodilation in diseases involving Aβ.

  8. Direct Proof of the In Vivo Pathogenic Role of the AChR Autoantibodies from Myasthenia Gravis Patients

    PubMed Central

    Kordas, Gregory; Lagoumintzis, George; Sideris, Sotirios; Poulas, Konstantinos; Tzartos, Socrates J.

    2014-01-01

    Several studies have suggested that the autoantibodies (autoAbs) against muscle acetylcholine receptor (AChR) of myasthenia gravis (MG) patients are the main pathogenic factor in MG; however, this belief has not yet been confirmed with direct observations. Although animals immunized with AChR or injected with anti-AChR monoclonal Abs, or with crude human MG Ig fractions exhibit MG symptoms, the pathogenic role of isolated anti-AChR autoAbs, and, more importantly, the absence of pathogenic factor(s) in the autoAb-depleted MG sera has not yet been shown by in vivo studies. Using recombinant extracellular domains of the human AChR α and β subunits, we have isolated autoAbs from the sera of four MG patients. The ability of these isolated anti-subunit Abs and of the Ab-depleted sera to passively transfer experimental autoimmune MG in Lewis rats was investigated. We found that the isolated anti-subunit Abs were at least as efficient as the corresponding whole sera or whole Ig in causing experimental MG. Abs to both α- and β-subunit were pathogenic although the anti-α-subunit were much more efficient than the anti-β-subunit ones. Interestingly, the autoAb-depleted sera were free of pathogenic activity. The later suggests that the myasthenogenic potency of the studied anti-AChR MG sera is totally due to their anti-AChR autoAbs, and therefore selective elimination of the anti-AChR autoAbs from MG patients may be an efficient therapy for MG. PMID:25259739

  9. Mathematical foundations of biomechanics.

    PubMed

    Niederer, Peter F

    2010-01-01

    The aim of biomechanics is the analysis of the structure and function of humans, animals, and plants by means of the methods of mechanics. Its foundations are in particular embedded in mathematics, physics, and informatics. Due to the inherent multidisciplinary character deriving from its aim, biomechanics has numerous connections and overlapping areas with biology, biochemistry, physiology, and pathophysiology, along with clinical medicine, so its range is enormously wide. This treatise is mainly meant to serve as an introduction and overview for readers and students who intend to acquire a basic understanding of the mathematical principles and mechanics that constitute the foundation of biomechanics; accordingly, its contents are limited to basic theoretical principles of general validity and long-range significance. Selected examples are included that are representative for the problems treated in biomechanics. Although ultimate mathematical generality is not in the foreground, an attempt is made to derive the theory from basic principles. A concise and systematic formulation is thereby intended with the aim that the reader is provided with a working knowledge. It is assumed that he or she is familiar with the principles of calculus, vector analysis, and linear algebra. PMID:21303323

  10. In Vitro Anti-AChE, Anti-BuChE, and Antioxidant Activity of 12 Extracts of Eleutherococcus Species

    PubMed Central

    2016-01-01

    Neurodegenerative diseases are one of the most occurring diseases in developed and developing countries. The aim of this work focused on the screening of the natural inhibitors of AChE and BuChE and antioxidants in Eleutherococcus species. We found that the ethanol extracts of E. setchuenensis and E. sessiliflorus showed the strongest inhibition towards AChE (IC50: 0.3 and 0.3 mg/mL, resp.). Among chloroform extracts, the most active appeared to be E. gracilistylus (IC50: 0.37 mg/mL). In turn, the ethanol extract of E. henryi inhibited the strongest BuChE with IC50 value of 0.13 mg/mL. Among chloroform extracts, E. gracilistylus, E. setchuenensis, and E. sessiliflorus appeared to be the strongest with IC50 values of 0.12, 0.18, and 0.19 mg/mL. HPTLC screening confirmed the presence of inhibitors in extracts. All extracts exhibited anti-DPPH⁎ activity and single antioxidants have been identified. To the best of our knowledge, no information was available on this activity of compounds in Eleutherococcus. These studies provide a biochemical basis for the regulation of AChE and BuChE and encourage us to continue isolation of active compounds. PMID:27803761

  11. In Vitro and In Vivo Profiles of ACH-702, an Isothiazoloquinolone, against Bacterial Pathogens▿

    PubMed Central

    Pucci, Michael J.; Podos, Steven D.; Thanassi, Jane A.; Leggio, Melissa J.; Bradbury, Barton J.; Deshpande, Milind

    2011-01-01

    ACH-702, a novel isothiazoloquinolone (ITQ), was assessed for antibacterial activity against a panel of Gram-positive and Gram-negative clinical isolates and found to possess broad-spectrum activity, especially against antibiotic-resistant Gram-positive strains, including methicillin-resistant Staphylococcus aureus (MRSA). For Gram-negative bacteria, ACH-702 showed exceptional potency against Haemophilus influenzae, Moraxella catarrhalis, and a Neisseria sp. but was less active against members of the Enterobacteriaceae. Good antibacterial activity was also evident against several anaerobes as well as Legionella pneumophila and Mycoplasma pneumoniae. Excellent bactericidal activity was observed for ACH-702 against several bacterial pathogens in time-kill assays, and postantibiotic effects (PAEs) of >1 h were evident with both laboratory and clinical strains of staphylococci at 10× MIC and similar in most cases to those observed for moxifloxacin at the same MIC multiple. In vivo efficacy was demonstrated against S. aureus with murine sepsis and thigh infection models, with decreases in the number of CFU/thigh equal to or greater than those observed after vancomycin treatment. Macromolecular synthesis assays showed specific dose-dependent inhibition of DNA replication in staphylococci, and biochemical analyses indicated potent dual inhibition of two essential DNA replication enzymes: DNA gyrase and topoisomerase IV. Additional biological data in support of an effective dual targeting mechanism of action include the following: low MIC values (≤0.25 μg/ml) against staphylococcal strains with single mutations in both gyrA and grlA (parC), retention of good antibacterial activity (MICs of ≤0.5 μg/ml) against staphylococcal strains with two mutations in both gyrA and grlA, and low frequencies for the selection of higher-level resistance (<10−10). These promising initial data support further study of isothiazoloquinolones as potential clinical candidates. PMID

  12. Isolation and characterization of pediocin AcH chimeric protein mutants with altered bactericidal activity.

    PubMed

    Miller, K W; Schamber, R; Osmanagaoglu, O; Ray, B

    1998-06-01

    A collection of pediocin AcH amino acid substitution mutants was generated by PCR random mutagenesis of DNA encoding the bacteriocin. Mutants were isolated by cloning mutagenized DNA into an Escherichia coli malE plasmid that directs the secretion of maltose binding protein-pediocin AcH chimeric proteins and by screening transformant colonies for bactericidal activity against Lactobacillus plantarum NCDO955 (K. W. Miller, R. Schamber, Y. Chen, and B. Ray, 1998. Appl. Environ. Microbiol. 64:14-20, 1998). In all, 17 substitution mutants were isolated at 14 of the 44 amino acids of pediocin AcH. Seven mutants (N5K, C9R, C14S, C14Y, G37E, G37R, and C44W) were completely inactive against the pediocin AcH-sensitive strains L. plantarum NCDO955, Listeria innocua Lin11, Enterococcus faecalis M1, Pediococcus acidilactici LB42, and Leuconostoc mesenteroides Ly. A C24S substitution mutant constructed by other means also was inactive against these bacteria. Nine other mutants (K1N, W18R, I26T, M31T, A34D, N41K, H42L, K43N, and K43E) retained from <1% to approximately 60% of wild-type activity when assayed against L. innocua Lin11. One mutant, K11E, displayed approximately 2. 8-fold-higher activity against this indicator. About one half of the mutations mapped to amino acids that are conserved in the pediocin-like family of bacteriocins. All four cysteines were found to be required for activity, although only C9 and C14 are conserved among pediocin-like bacteriocins. Several basic amino acids as well as nonpolar amino acids located within the hydrophobic C-terminal region also were found to be important. The mutations are discussed in the context of structural models that have been proposed for the bacteriocin.

  13. Preliminary Geological Maps of the Ac-H-10 Rongo and Ac-H-15 Zadeni Quadrangles: An integrated Mapping Study Using Dawn Spacecraft Data

    NASA Astrophysics Data System (ADS)

    Platz, T.; Nathues, A.; Crown, D. A.; Mest, S. C.; Williams, D. A.; Hoffmann, M.; Schäfer, M.; Sizemore, H. G.; Yingst, R. A.; Ruesch, O.; Buczkowski, D.; Kneissl, T.; Schmedemann, N.; Hughson, K.; Preusker, F.; Russell, C. T.

    2015-12-01

    We used geologic mapping applied to Dawn spacecraft data as a tool to understand the geologic history of the Ac-H-10 Rongo and Ac-H-15 Zadeni quadrangles of dwarf planet Ceres. These regions, Rongo and Zadeni, are located between 22°S-22°N and 288°-360°E and 65-90°S and 0°-360°E, respectively. The Rongo Quadrangle hosts a number of features: 1) the southwest portion is dissected by curvilinear structures likely caused by Yalode basin formation; 2) the central part is marked by dome-like constructs up to 100 km across; 3) a peculiar bright, c.4 km tall, conical structure informally known as the 'pyramid'; 4) impact craters of various diameters appear moderately to highly degraded or are partially buried; and 5) bright material is primarily exposed in the central portion and often associated with craters. Rongo crater (68 km across) exhibits a central peak and scalloped walls indicative of its degraded appearance. The Zadeni Quadrangle is characterised by impact craters up to 130 km in diameter of which Zadeni crater is the largest. Impact craters across all sizes exhibit fresh to highly degraded morphologies or are partially buried. Many craters developed central peaks. Inter-crater plains are generally hummocky with isolated regions of smooth-textured surfaces. The south pole area (85-90°S) is poorly illuminated and may host a large impact structure. At the time of this writing geologic mapping was performed on Framing Camera (FC) mosaics from Approach (1.3 km/px) and Survey (415 m/px) orbits, including clear filter and colour images and digital terrain models derived from stereo images. In Fall 2015 images from the High Altitude Mapping Orbit (140 m/px) will be used to refine the mapping, followed by Low Altitude Mapping Orbit (35 m/px) starting in December 2015. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA through the Dawn project, and from the German and Italian Space Agencies.

  14. Age-dependency in hunting ability among the Ache of eastern Paraguay.

    PubMed

    Walker, Robert; Hill, Kim; Kaplan, Hillard; McMillan, Garnett

    2002-06-01

    This paper examines changes in hunting ability across the lifespan for the Ache of eastern Paraguay. Hunting ability is decomposed into two components-finding prey and probability of kill upon encounter- and analyzed for important prey species. Results support the argument that skill acquisition is an important aspect of the human foraging niche with hunting outcome variables reaching peaks surprisingly late in life, significantly after peaks in strength. The implications of this study are important for modeling the role of the human foraging niche in the co-evolution of various outstanding human life history characteristics such as large brains, long lifespans, and extended juvenile periods.

  15. The foundation of physicianship.

    PubMed

    Fuks, Abraham; Brawer, James; Boudreau, J Donald

    2012-01-01

    Although the practice of medicine continually changes in response to new biomedical understanding, novel technologies, and evolving cultural contexts, the ethical foundations of the clinical relationship between patient and physician paradoxically remain constant. There are fundamental characteristics with respect to character, behavior, and responsibilities that are descriptive of and necessary to the role of healer and that underpin the notion of physicianship. This article discusses the underlying characteristics or virtues that are necessary to the practice of medicine from the perspectives of three different philosophic traditions: the Aristotelian idea of phronesis as developed in the work of Edmund Pellegrino; the notion of alterity as framed by Emmanuel Levinas; and the attributes necessary to healing as laid out in the kabbala.

  16. Foundations of Geomagnetism

    NASA Astrophysics Data System (ADS)

    Jackson, Andy

    The study of the magnetic field of the Earth, or geomagnetism, is one of the oldest lines of scientific enquiry. Indeed, it has often been said that William Gilbert's De Magnete, published in 1600 and predating Isaac Newton's Principia by 87 years, can claim to be the first true scientific textbook; his study was essentially the first of academic rather than practical interest.What then, we may ask, has been accomplished in the nearly 400 intervening years up to the publication of Foundations of Geomagnetism? In short, a wealth of observational evidence, considerable physical understanding, and a great deal of mathematical apparatus have accrued, placing the subject on a much surer footing.The latter two categories are described in considerable detail, and with attendant rigor, in this book. The sphericity of the Earth means that a frequent theme in the book is the solution of the partial differential equations of electrodynamics in a spherical geometry.

  17. Muscle-specific kinase (MuSK) autoantibodies suppress the MuSK pathway and ACh receptor retention at the mouse neuromuscular junction

    PubMed Central

    Ghazanfari, Nazanin; Morsch, Marco; Reddel, Stephen W; Liang, Simon X; Phillips, William D

    2014-01-01

    Muscle-specific kinase (MuSK) autoantibodies from myasthenia gravis patients can block the activation of MuSK in vitro and/or reduce the postsynaptic localization of MuSK. Here we use a mouse model to examine the effects of MuSK autoantibodies upon some key components of the postsynaptic MuSK pathway and upon the regulation of junctional ACh receptor (AChR) numbers. Mice became weak after 14 daily injections of anti-MuSK-positive patient IgG. The intensity and area of AChR staining at the motor endplate was markedly reduced. Pulse-labelling of AChRs revealed an accelerated loss of pre-existing AChRs from postsynaptic AChR clusters without a compensatory increase in incorporation of (newly synthesized) replacement AChRs. Large, postsynaptic AChR clusters were replaced by a constellation of tiny AChR microaggregates. Puncta of AChR staining also appeared in the cytoplasm beneath the endplate. Endplate staining for MuSK, activated Src, rapsyn and AChR were all reduced in intensity. In the tibialis anterior muscle there was also evidence that phosphorylation of the AChR β-subunit-Y390 was reduced at endplates. In contrast, endplate staining for β-dystroglycan (through which rapsyn couples AChR to the synaptic basement membrane) remained intense. The results suggest that anti-MuSK IgG suppresses the endplate density of MuSK, thereby down-regulating MuSK signalling activity and the retention of junctional AChRs locally within the postsynaptic membrane scaffold. PMID:24860174

  18. Methadone's effect on nAChRs--a link between methadone use and smoking?

    PubMed

    Talka, Reeta; Tuominen, Raimo K; Salminen, Outi

    2015-10-15

    Methadone is a long-acting opioid agonist that is frequently prescribed as a treatment for opioid addiction. Almost all methadone maintenance patients are smokers, and there is a correlation between smoking habit and use of methadone. Methadone administration increases tobacco smoking, and heavy smokers use higher doses of methadone. Nevertheless, methadone maintenance patients are willing to quit smoking although their quit rates are low. Studies on nicotine-methadone interactions provide an example of the bedside-to-bench approach, i.e., observations in clinical settings have been studied experimentally in vivo and in vitro. In vivo studies have revealed the interplay between nicotine and the endogenous opioid system. At the receptor level, methadone has been shown to be an agonist of human α7 nAChRs and a non-competitive antagonist of human α4β2 and α3* nAChRs. These drugs do not have significant interactions at the level of drug metabolism, and thus the interaction is most likely pharmacodynamic. The net effect of the interaction may depend on individual characteristics because pharmacogenetic factors influence the disposition of both methadone and nicotine. PMID:26231941

  19. The significance of aches/pains among workers in an electronics factory.

    PubMed

    Ho, S F; Phoon, W H

    1997-06-01

    Three hundred and fifteen female workers with at least three months' employment history in a factory manufacturing disk drives were studied. Each worker completed a self-administered questionnaire on their personal particulars, hours of work, opinion on the work and the workplace and the presence and severity of aches/pains experienced over the past one month. One hundred and forty one (44.8%) of the workers had complaints of aches/pains. Of these, 81 (57.5%) reported an improvement in their symptoms during their off-days. 59 (41.8%) had symptoms affecting two or more sites. The most commonly affected sites were the hands and shoulders, followed by the head and back. There was no significant difference in the prevalence of symptoms between workers from the different work stations. Ninety four (66.7%) of these workers reported that the pains that were severe enough to affect their activities. 76 (53.9%) had to seek some form of medical treatment while 33 (23.4%) had to be on medical leave. However, the physical examinations of this group of workers were normal. The symptoms appeared to be influenced by their attitude towards work. A significantly higher number of workers with symptoms expressed dissatisfaction with work and had complaints of a noisy and cold environment. The study showed that workers' morale and the quality of the work environment may play an important role in improving their general well-being.

  20. Nicotinic Acetylcholine Receptor (nAChR) Dependent Chorda Tympani Taste Nerve Responses to Nicotine, Ethanol and Acetylcholine.

    PubMed

    Ren, Zuo Jun; Mummalaneni, Shobha; Qian, Jie; Baumgarten, Clive M; DeSimone, John A; Lyall, Vijay

    2015-01-01

    Nicotine elicits bitter taste by activating TRPM5-dependent and TRPM5-independent but neuronal nAChR-dependent pathways. The nAChRs represent common targets at which acetylcholine, nicotine and ethanol functionally interact in the central nervous system. Here, we investigated if the nAChRs also represent a common pathway through which the bitter taste of nicotine, ethanol and acetylcholine is transduced. To this end, chorda tympani (CT) taste nerve responses were monitored in rats, wild-type mice and TRPM5 knockout (KO) mice following lingual stimulation with nicotine free base, ethanol, and acetylcholine, in the absence and presence of nAChR agonists and antagonists. The nAChR modulators: mecamylamine, dihydro-β-erythroidine, and CP-601932 (a partial agonist of the α3β4* nAChR), inhibited CT responses to nicotine, ethanol, and acetylcholine. CT responses to nicotine and ethanol were also inhibited by topical lingual application of 8-chlorophenylthio (CPT)-cAMP and loading taste cells with [Ca2+]i by topical lingual application of ionomycin + CaCl2. In contrast, CT responses to nicotine were enhanced when TRC [Ca2+]i was reduced by topical lingual application of BAPTA-AM. In patch-clamp experiments, only a subset of isolated rat fungiform taste cells exposed to nicotine responded with an increase in mecamylamine-sensitive inward currents. We conclude that nAChRs expressed in a subset of taste cells serve as common receptors for the detection of the TRPM5-independent bitter taste of nicotine, acetylcholine and ethanol.

  1. ACh and 5-HT stimulated thermogenesis at different core temperatures in the He-Cold hypothermic hamster.

    PubMed

    Simpson, C W; Resch, G E

    1985-08-01

    Hamsters in deep experimentally induced hypothermia, at body temperatures between 7 degrees C and 11.5 degrees C, were microinjected with 5-HT and ACh at brain sites in the anterior-preoptic area of the hypothalamus (AH/POA). ACh or 5-HT was injected into an AH/POA site at different starting core temperatures in different groups of hypothermic hamsters. Colonic temperatures (Tc) were maintained, following He-Cold induction, in a temperature controlled environmental chamber and measured with a YSI thermister probe and YSI telethermometer. Injections of either 5-HT or ACh at Tc's between 7.0 degrees C and 9.0 degrees C elicited only modest increases in Tc i.e., 0.3 degrees C--0.6 degrees C, respectively. As Tc increased, however, to ranges between 9.1 degrees C--10.0 degrees C and in different animals to greater than 10 degrees C both ACh and 5-HT at the same sites elicited significant increases in Tc, 1.5 degrees C for 5-HT and 2.2 degrees C for ACh compared to saline injections. These data suggest that at the lowest Tc's we are observing a "cold block" of temperature sensitive sites in the AH/POA. Increasing the starting Tc beyond 9.0 degrees C however, evokes significant increases in heat-gain following AH/POA injection of either ACh or 5-HT. These data are consistent with Myers' observations concerning the organization of heat-gain mechanisms at AH/POA sites. In addition, they suggest that both the afferent limb of the heat-gain circuit (5-HT) and the efferent limb of the circuit (ACh) are functionally impaired when Tc is close to the physiological limit in the He-Cold hypothermic hamster.

  2. Activity of nAChRs Containing α9 Subunits Modulates Synapse Stabilization via Bidirectional Signaling Programs

    PubMed Central

    Murthy, Vidya; Taranda, Julián; Elgoyhen, A. Belén; Vetter, Douglas E.

    2010-01-01

    Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) α9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR α9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in α9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the α9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult α9 null mice. Finally, by using mice expressing the nondesensitizing α9 L9′T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation. PMID:19790106

  3. Creating a Successful Affiliated Foundation. Foundation Relations. Board Basics.

    ERIC Educational Resources Information Center

    Hedgepeth, Royster C.

    1999-01-01

    This booklet for trustees of institutions of higher education offers guidelines for the creation of effective affiliated foundations. An introductory section notes the increased use of such foundations by public colleges and universities for institutional fund-raising and management of property and endowments. The booklet finds that successful…

  4. Foundations of resilience thinking.

    PubMed

    Curtin, Charles G; Parker, Jessica P

    2014-08-01

    Through 3 broad and interconnected streams of thought, resilience thinking has influenced the science of ecology and natural resource management by generating new multidisciplinary approaches to environmental problem solving. Resilience science, adaptive management (AM), and ecological policy design (EPD) contributed to an internationally unified paradigm built around the realization that change is inevitable and that science and management must approach the world with this assumption, rather than one of stability. Resilience thinking treats actions as experiments to be learned from, rather than intellectual propositions to be defended or mistakes to be ignored. It asks what is novel and innovative and strives to capture the overall behavior of a system, rather than seeking static, precise outcomes from discrete action steps. Understanding the foundations of resilience thinking is an important building block for developing more holistic and adaptive approaches to conservation. We conducted a comprehensive review of the history of resilience thinking because resilience thinking provides a working context upon which more effective, synergistic, and systems-based conservation action can be taken in light of rapid and unpredictable change. Together, resilience science, AM, and EPD bridge the gaps between systems analysis, ecology, and resource management to provide an interdisciplinary approach to solving wicked problems.

  5. Foundations of resilience thinking.

    PubMed

    Curtin, Charles G; Parker, Jessica P

    2014-08-01

    Through 3 broad and interconnected streams of thought, resilience thinking has influenced the science of ecology and natural resource management by generating new multidisciplinary approaches to environmental problem solving. Resilience science, adaptive management (AM), and ecological policy design (EPD) contributed to an internationally unified paradigm built around the realization that change is inevitable and that science and management must approach the world with this assumption, rather than one of stability. Resilience thinking treats actions as experiments to be learned from, rather than intellectual propositions to be defended or mistakes to be ignored. It asks what is novel and innovative and strives to capture the overall behavior of a system, rather than seeking static, precise outcomes from discrete action steps. Understanding the foundations of resilience thinking is an important building block for developing more holistic and adaptive approaches to conservation. We conducted a comprehensive review of the history of resilience thinking because resilience thinking provides a working context upon which more effective, synergistic, and systems-based conservation action can be taken in light of rapid and unpredictable change. Together, resilience science, AM, and EPD bridge the gaps between systems analysis, ecology, and resource management to provide an interdisciplinary approach to solving wicked problems. PMID:24975863

  6. Ford Foundation Fellowships

    NASA Astrophysics Data System (ADS)

    The Ford Foundation is sponsoring 40 three-year predoctoral fellowships and 10 one-year dissertation fellowships for minorities for 1987. The predoctoral fellowships include an annual stipend of $10,000 and an annual grant of $6000 to the fellow's institution in lieu of tuition and fees. Dissertation Fellows will receive a stipend of $18,000 and no institutional grant.The program is designed to increase the presence of under represented minorities in the nation's college and university faculties. The minority groups to be considered under this program are: American Indians, Alaskan Natives (Eskimo or Aleut), Black Americans, Mexican Americans/Chicanos, Native Pacific Islanders (Polynesians or Micronesians), and Puerto Ricans. The competition is open to any U.S. citizen who is a member of one of these groups, who is a beginning graduate student or is within 1 year of completing the dissertation, and who expects to work toward a Ph.D. or Sc.D. degree. Fellowships will be awarded in the behavioral and social sciences, humanities, engineering, mathematics, physical sciences, and biological sciences. The National Research Council, which is administering the fellowships, can provide more information on which fields of study are and are not eligible for this program.

  7. Acetylcholine as a signaling system to environmental stimuli in plants. III. Asymmetric solute distribution controlled by ACh in gravistimulated maize seedlings.

    PubMed

    Momonoki, Y S; Hineno, C; Noguchi, K

    1998-01-01

    Asymmetric distribution of acetylcholinesterase (AChE) activity has previously been demonstrated to occur in the lower side of the gravity-stimulated maize shoot. The localization of immunoreacted IAA-inositol synthase, AChE and safranin was detected in selected organs of gravistimulated dark grown maize seedlings using a light microscope. Immunoreacted IAA-inositol synthase was asymmetrically distributed in the lower side of the stele of coleoptile node and mesocotyl in maize seedlings placed horizontally. The positive AChE spots in the coleoptile node and mesocotyl were apparently localized in the lower half of the gravistimulated seedlings. Safranin was also asymmetrically distributed in the lower half of the endodermis and stele cells of coleoptile node and mesocotyl. Namely, transport of safranin in the upper half of the coleoptile node and mesocotyl was blocked by gravistimulation. Furthermore, the asymmetric distribution of immunoreacted IAA-inositol synthase was inhibited by neostigmine bromide, AChE inhibitor. These results show that an asymmetric environmental stimulus induces changes in AChE activity, affecting IAA-inositol synthase localization and safranin transport. PMID:12162322

  8. Concomitant alpha7 and beta2 nicotinic AChR subunit deficiency leads to impaired energy homeostasis and increased physical activity in mice.

    PubMed

    Somm, Emmanuel; Guérardel, Audrey; Maouche, Kamel; Toulotte, Audrey; Veyrat-Durebex, Christelle; Rohner-Jeanrenaud, Françoise; Maskos, Uwe; Hüppi, Petra S; Schwitzgebel, Valérie M

    2014-05-01

    Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated cation channels well characterized in neuronal signal transmission. Moreover, recent studies have revealed nAChR expression in nonneuronal cell types throughout the body, including tissues involved in metabolism. In the present study, we screen gene expression of nAChR subunits in pancreatic islets and adipose tissues. Mice pancreatic islets present predominant expression of α7 and β2 nAChR subunits but at a lower level than in central structures. Characterization of glucose and energy homeostasis in α7β2nAChR(-/-) mice revealed no major defect in insulin secretion and sensitivity but decreased glycemia apparently unrelated to gluconeogenesis or glycogenolysis. α7β2nAChR(-/-) mice presented an increase in lean and bone body mass and a decrease in fat storage with normal body weight. These observations were associated with elevated spontaneous physical activity in α7β2nAChR(-/-) mice, mainly due to elevation in fine vertical (rearing) activity while their horizontal (ambulatory) activity remained unchanged. In contrast to α7nAChR(-/-) mice presenting glucose intolerance and insulin resistance associated to excessive inflammation of adipose tissue, the present metabolic phenotyping of α7β2nAChR(-/-) mice revealed a metabolic improvement possibly linked to the increase in spontaneous physical activity related to central β2nAChR deficiency.

  9. Evidence for the exclusive expression of functional homomeric α7 nAChRs in hypothalamic histaminergic tuberomammillary neurons in rats.

    PubMed

    Tischkau, Shelley; Mhaskar, Yashanad; Uteshev, Victor V

    2014-03-20

    Hypothalamic histaminergic tuberomammillary (TM) neurons in rats express high densities of nicotinic acetylcholine receptors (nAChRs) whose Ca(2+) permeability, kinetic and pharmacological properties are similar to those of heterologous homomeric α7 nAChRs. However, native α7 nAChR subunits can co-assemble with β or α5 nAChR subunits to form functional heteromeric α7-containing α7β or α7α5 nAChRs with kinetics and pharmacology similar to those of α7 homomers. Therefore, although TM nAChRs have been used as an ex vivo model of functional α7 homomers, the molecular makeup of TM nAChRs has not been determined and the expression of functional α7-containing heteromers in TM neurons has not been excluded. To determine the profile of TM nAChR subunit transcripts, we have conducted single-cell qRT-PCR experiments using acutely dissociated TM neurons in rats. TM neurons were found to express transcripts of only principal α3, α6 and α7 nAChR subunits. Transcripts of other known mammalian neuronal subunits (α2, α4-5, α9-10, β2-4) were not detected. In the absence of β and α5 subunits, the expression of functional α7-containing heteromers in TM neurons is highly unlikely because principal α3, α6 and α7 nAChR subunits alone are not known to form functional heteromeric nAChRs. These results support the exclusive expression of native functional α7 homomers in rat TM neurons and introduce these neurons as a unique reliable source of native functional homomeric α7 nAChRs suitable for ex vivo and in vitro pharmacological assays in developing selective α7 nAChR agents.

  10. Going up in Smoke? A Review of nAChRs-based Treatment Strategies for Improving Cognition in Schizophrenia

    PubMed Central

    Boggs, Douglas L.; Carlson, Jon; Cortes-Briones, Jose; Krystal, John H.; D’Souza, D. Cyril

    2015-01-01

    Cognitive impairment is known to be a core deficit in schizophrenia. Existing treatments for schizophrenia have limited efficacy against cognitive impairment. The ubiquitous use of nicotine in this population is thought to reflect an attempt by patients to self-medicate certain symptoms associated with the illness. Concurrently there is evidence that nicotinic receptors that have lower affinity for nicotine are more important in cognition. Therefore, a number of medications that target nicotinic acetylcholine receptors (nAChRs) have been tested or are in development. In this article we summarize the clinical evidence of nAChRs dysfunction in schizophrenia and review clinical studies testing either nicotine or nicotinic medications for the treatment of cognitive impairment in schizophrenia. Some evidence suggests beneficial effects of nAChRs based treatments for the attentional deficits associated with schizophrenia. Standardized cognitive test batteries have failed to capture consistent improvements from drugs acting at nAChRs. However, more proximal measures of brain function, such as ERPs relevant to information processing impairments in schizophrenia, have shown some benefit. Further work is necessary to conclude that nAChRs based treatments are of clinical utility in the treatment of cognitive deficits of schizophrenia. PMID:24345265

  11. Nicotinic acetylcholine receptors: a comparison of the nAChRs of Caenorhabditis elegans and parasitic nematodes.

    PubMed

    Holden-Dye, Lindy; Joyner, Michelle; O'Connor, Vincent; Walker, Robert J

    2013-12-01

    Nicotinic acetylcholine receptors (nAChRs) play a key role in the normal physiology of nematodes and provide an established target site for anthelmintics. The free-living nematode, Caenorhabditis elegans, has a large number of nAChR subunit genes in its genome and so provides an experimental model for testing novel anthelmintics which act at these sites. However, many parasitic nematodes lack specific genes present in C. elegans, and so care is required in extrapolating from studies using C. elegans to the situation in other nematodes. In this review the properties of C. elegans nAChRs are reviewed and compared to those of parasitic nematodes. This forms the basis for a discussion of the possible subunit composition of nAChRs from different species of parasitic nematodes. Currently our knowledge on this is largely based on studies using heterologous expression and pharmacological analysis of receptor subunits in Xenopus laevis oocytes. It is concluded that more information is required regarding the subunit composition and pharmacology of endogenous nAChRs in parasitic nematodes. PMID:23500392

  12. Geological Mapping of the Ac-H-10 Rongo and Ac-H-15 Zadeni quadrangles of Ceres from NASA's Dawn Mission.

    NASA Astrophysics Data System (ADS)

    Platz, Thomas; Nathues, Andreas; Sizemore, Hanna; Ruesch, Ottaviano; Hoffmann, Martin; Schaefer, Michael; Crown, David; Mest, Scott; Aileen Yingst, R.; Williams, David; Buczkowski, Debra; Hughson, Kynan; Kneissl, Thomas; Schmedemann, Nico; Schorghofer, Norbert; Nass, Andrea; Preusker, Frank; Russell, Christopher

    2016-04-01

    On March 6, 2015 NASA's Dawn spacecraft arrived at (1) Ceres, the largest object in the main asteroid belt. Dawn is studying the dwarf planet more than one year through successively lower orbits at increasing resolution. Main orbital phases include Survey Orbit, High Altitude Mapping Orbit (HAMO), and Low Altitude Mapping Orbit (LAMO) where Framing Camera (FC) [1] resolution increased from c.400 m/px to c.140 m/px and c.35 m/px, respectively. The Dawn Science Team is conducting geological mapping campaigns for Ceres (as done before for Vesta [2,3]) and includes the production of a Survey/HAMO-based global geological map and a series of 15 LAMO-based geological quadrangle maps. This abstract presents HAMO-based geological maps of Ac-H-10 Rongo (22°N-22°S, 288-360°E) and Ac-H-15 Zadeni (65°-90°S, 0°-360°E) quadrangles. The Rongo Quadrangle is located at the equatorial region and comprises the unique isolated mountain Ahuna Mons (10.5°S/316.0°E; formerly known as the pyramid), abundant impact craters spanning a range in diameters and states of preservation - from fresh to highly degraded - , and a number of tholi, which may represent surface expressions of sub-surface diapir intrusions. The SW portion of the quandrangle is characterised by Yalode (D=260 km) sourced ejecta. The Zadeni Quadrangle is dominated by the 122-km-diameter crater Zadeni located at 70.2°S/37.4°E) and a suite of mid-sized craters whose morphologies range from fresh to highly degraded. Portions of the quadrangle are covered by Urvara [4] and Yalode [5] ejecta materials. The South Polar Region is poorly illuminated and the South Pole itself is likely located within a larger impact structure. Future work of this mapping campaign includes revision of HAMO-based line work (e.g., contacts) with higher resolution LAMO data. Final interpretations regarding the geological histories of these two quadrangles will also be based on FC colour and stereo-derived topography data, VIR spectra as well

  13. The dual-acting AChE inhibitor and H3 receptor antagonist UW-MD-72 reverses amnesia induced by scopolamine or dizocilpine in passive avoidance paradigm in rats.

    PubMed

    Sadek, Bassem; Khan, Nadia; Darras, Fouad H; Pockes, Steffen; Decker, Michael

    2016-10-15

    Both the acetylcholine esterase (AChE) and the histamine H3 receptor (H3R) are involved in the metabolism and modulation of acetylcholine release and numerous other centrally acting neurotransmitters. Hence, dual-active AChE inhibitors (AChEIs) and H3R antagonists hold potential to treat cognitive disorders like Alzheimer's disease (AD). The novel dual-acting AChEI and H3R antagonist 7-(3-(piperidin-1-yl)propoxy)-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one (UW-MD-72) shows excellent selectivity profiles over the AChE's isoenzyme butyrylcholinesterase (BChE) as well as high and balanced in-vitro affinities at both AChE and hH3R with IC50 of 5.4μM on hAChE and hH3R antagonism with Ki of 2.54μM, respectively. In the current study, the effects of UW-MD-72 (1.25, 2.5, and 5mg/kg, i.p.) on memory deficits induced by the muscarinic cholinergic antagonist scopolamine (SCO) and the non-competitive N-methyl-d-aspartate (NMDA) antagonist dizocilpine (DIZ) were investigated in a step-through type passive avoidance paradigm in adult male rats applying donepezil (DOZ) and pitolisant (PIT) as reference drugs. The results observed show that SCO (2mg/kg, i.p.) and DIZ (0.1mg/kg, i.p.) significantly impaired learning and memory in rats. However, acute systemic administration of UW-MD-72 significantly ameliorated the SCO- and DIZ-induced amnesic effects. Furthermore, the ameliorating activity of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was partly reversed when rats were pretreated with the centrally-acting H2R antagonist zolantidine (ZOL, 10mg/kg, i.p.), but not with the CNS penetrant H1R antagonist pyrilamine (PYR, 10mg/kg, i.p.). Moreover, ameliorative effect of UW-MD-72 (1.25mg/kg, i.p.) in DIZ-induced amnesia was strongly reversed when rats were pretreated with a combination of ZOL (10mg/kg, i.p.) and SCO (1.0mg/kg, i.p.), indicating that these memory enhancing effects were, in addition to other neural circuits, observed through histaminergic H2R as well as

  14. Geologic Mapping of the Ac-H-1 quadrangle of Ceres from NASA's Dawn mission

    NASA Astrophysics Data System (ADS)

    Rüsch, Ottaviano; McFadden, Lucy A.; Hiesinger, Harald; Scully, Jennifer; Kneissl, Thomas; Hughson, Kynan; Williams, David A.; Roatsch, Thomas; Platz, Thomas; Preusker, Frank; Schmedemann, Nico; Marchi, Simone; Jaumann, Ralf; Nathues, Andreas; Raymond, Carol A.; Russell, Christopher T.

    2016-04-01

    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta (1, 2), including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map, and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract, we present the geologic map and geologic evolution of the Ac-H-1 Asari Quadrangle. At the time of writing, LAMO images (35 m/pixel) are just becoming available. Thus, our geologic maps are based on HAMO images (140 m/pixel) and HAMO and Survey (400 m/pixel) digital terrain models (for topographic information) (3). Dawn Framing Camera (FC) color images are also used to provide context for map unit identification. The maps to be presented as posters will be updated from analyses of LAMO images. Ac-H-1 quadrangle covers the North Pole area: 65°N-90°N. Key characteristics of the study area are: (i) a high density of impact craters and (ii) only moderate topographic variations across the quadrangle. We measured a crater density of 9.8E-04 km-2 for crater diameters >10 km, the highest on Ceres measured so far. Topographic lows, reaching -4 km, correspond to the floors of impact craters with diameters up to 64 km. A few isolated topographic highs (plateaus), reaching ~5 km in altitude relative to the ellipsoid are present. Their irregular shape is often sculpted by impacts. A peculiar topographic rise is represented by Ysolo Mons: a ~5 km high and ~20 km wide mountain. No downslope striations are preserved on the Mons flanks, indicating an older surface relative to Ahuna Mons, a similar but morphologically fresh appearing mountain at the equator (quadrangle Ac-H-10, (4)). Several impact craters show central peaks and/or mass wasting deposits on their floor. Crater rims often display terraces. These morphologies show varying degrees of degradation. Uncommon crater morphologies are a smooth crater floor (crater located at 79°N-170°E) and a large mass wasting landform inside

  15. Establishing a Local Education Foundation.

    ERIC Educational Resources Information Center

    Pressley, James S.; Markland, Maureen S.

    This paper describes the process of establishing local education foundations for the purpose of raising revenues to supplement, not supplant, existing school programs. Plans to identify funding sources and define the purpose of the foundation tied to student and academic achievement must emerge in order to solicit private individuals or groups,…

  16. Theoretical Foundations of Learning Environments

    ERIC Educational Resources Information Center

    Jonassen, David H., Ed.; Land, Susan M., Ed.

    1999-01-01

    "Theoretical Foundations of Learning Environments" describes the most contemporary psychological and pedagogical theories that are foundations for the conception and design of open-ended learning environments and new applications of educational technologies. In the past decade, the cognitive revolution of the 60s and 70s has been replaced or…

  17. Cornelia de Lange Syndrome Foundation

    MedlinePlus

    ... online suggestion box . Mailing Address: Cornelia de Lange Syndrome Foundation 302 West Main Street, #100 Avon, Connecticut 06001 USA What Is CdLS? Who We Are What We Do Research Get Involved Find Support ... & Terms Site Map The Cornelia de Lange Syndrome (CdLS) Foundation is a family support organization that ...

  18. Foundation Degrees: A Risky Business?

    ERIC Educational Resources Information Center

    Rowley, Jennifer

    2005-01-01

    Purpose: Foundation degrees, the new proposal for sub-degree vocational education in the UK, are characterised by innovation both in their design (curriculum, teaching, learning and assessment) and in the marketplace for which they are designed. This article argues that the development and delivery of foundation degrees carry a high level of risk,…

  19. The Psychological Foundations of Mathematics.

    ERIC Educational Resources Information Center

    Suppes, Patrick

    1967-01-01

    This paper outlines problems which are central to the psychological foundations of mathematics. Discussed are the relations that exist between psychological and classical foundations of mathematics. It is shown how the inadequacies of current learning theories which account for complex mathematics learning may be made explicit for appropriate…

  20. Functionality and stability data of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology.

    PubMed

    Padilla-Morales, Luis F; Colón-Sáez, José O; González-Nieves, Joel E; Quesada-González, Orestes; Lasalde-Dominicci, José A

    2016-03-01

    The presented data provides additional information about the assessment of affinity purified nicotinic acetylcholine receptor (nAChR) rich membrane solubilized with long chain (16 saturated carbons) lysophospholipid with glycerol headgroup (LFG-16). The assessment of stability and functionality of solubilized membrane protein is a critical step prior to further crystallization trails. One of the key factors for this task is the appropriate choice of a detergent that can support nAChR activity and stability comparable to the crude membranes. The stability of the nAChR-LFG-16 complex incorporated into lipid cubic phase (LCP) was monitored for a period of 30 days by means of fluorescence recovery after photobleaching (FRAP) and the functionality was evaluated after its incorporation into Xenopus oocyte by means of the two electrode voltage clamp technique. PMID:26870753

  1. Auger electron spectroscopy, secondary ion mass spectroscopy and optical characterization of a-C-H and BN films

    NASA Technical Reports Server (NTRS)

    Pouch, J. J.; Alterovitz, S. A.; Warner, J. D.

    1986-01-01

    The amorphous dielectrics a-C:H and BN were deposited on III-V semiconductors. Optical band gaps as high as 3 eV were measured for a-C:H generated by C4H10 plasmas; a comparison was made with bad gaps obtained from films prepared by CH4 glow discharges. The ion beam deposited BN films exhibited amorphous behavior with band gaps on the order of 5 eV. Film compositions were studied by Auger electron spectroscopy (AES), x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The optical properties were characterized by ellipsometry, UV/VIS absorption, and IR reflection and transmission. Etching rates of a-C:H subjected to O2 dicharges were determined.

  2. Electron cyclotron resonance deposition and plasma diagnostics of a-Si:H and a-C:H films

    NASA Technical Reports Server (NTRS)

    Shing, Y. H.

    1989-01-01

    Amorphous silicon (a-Si:H) and amorphous carbon (a-C:H) films deposited by electron cyclotron resonance (ECR) microwave plasma-enhanced chemical vapor deposition are discussed. It is shown that the ECR microwave plasma deposition technique can produce a-Si:H films with material qualities similar to and with a deposition rate one order of magnitude higher than for films deposited by radio-frequency glow discharge. The ECR-deposited a-C:H films are characterized by fluorescence, IR, and Raman spectroscopy. In situ optical emission spectroscopy plasma diagnostics indicates that ECR plasmas have a strong emission at 434 nm, which indicates a higher chemical reactivity than radio-frequency glow discharge plasmas. The radio frequency bias to the substrate is found to play a critical role in determining the film structure and the carbon bonding configuration of ECR-deposited a-C:H films.

  3. Erosion of a-C:H in the afterglow of ammonia plasma

    NASA Astrophysics Data System (ADS)

    Drenik, Aleksander; Mourkas, Angelos; Zaplotnik, Rok; Primc, Gregor; Mozetič, Miran; Panjan, Peter; Alegre, Daniel; Tabarés, Francisco L.

    2016-07-01

    Amorphous hydrogenated carbon (a-C:H) deposits were eroded in the afterglow of a NH3 plasma, created with an inductively coupled RF generator in pure NH3 at the gas pressure of 50 Pa. The plasma system was characterised by optical emission spectroscopy and mass spectrometry, and the erosion process was monitored in-situ with a laser interferometry system. Based on the mass spectrometry measurements, the degree of dissociation of the NH3 molecules was estimated at 90% at the highest generator forward power in the discharge region, however the densities of N and H atoms were significantly smaller at the location of the sample holder. The erosion rates were found to increase with surface temperature and forward generator power. In the high dissociation regime, the composition of the afterglow and the reaction products highlight the role of N atoms in the erosion process.

  4. Rapid thermal annealing of Amorphous Hydrogenated Carbon (a-C:H) films

    NASA Technical Reports Server (NTRS)

    Alterovitz, Samuel A.; Pouch, John J.; Warner, Joseph D.

    1987-01-01

    Amorphous hydrogenated carbon (a-C:H) films were deposited on silicon and quartz substrates by a 30 kHz plasma discharge technique using methane. Rapid thermal processing of the films was accomplished in nitrogen gas using tungsten halogen light. The rapid thermal processing was done at several fixed temperatures (up to 600 C), as a function of time (up to 1800 sec). The films were characterized by optical absorption and by ellipsometry in the near UV and the visible. The bandgap, estimated from extrapolation of the linear part of a Tauc plot, decreases both with the annealing temperature and the annealing time, with the temperature dependence being the dominating factor. The density of states parameter increases up to 25 percent and the refractive index changes up to 20 percent with temperature increase. Possible explanations of the mechanisms involved in these processes are discussed.

  5. Deposition of a-C:H films on inner surface of high-aspect-ratio microchannel

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Choi, Junho

    2016-08-01

    Hydrogenated amorphous carbon (a-C:H) films were prepared on inner surface of 100-μm-width microchannel by using a bipolar-type plasma based ion implantation and deposition. The microchannel was fabricated using a silicon plate, and two kinds of microchannels were prepared, namely, with a bottom layer (open at one end) and without a bottom layer (open at both ends). The distribution of thickness and hardness of films was evaluated by SEM and nanoindentation measurements, respectively, and the microstructures of films were evaluated by Raman spectroscopy. Furthermore, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision and Direct Simulation Monte Carlo to investigate the coating mechanism for the microchannel. It was found that the film thickness decreased as the depth of the coating position increased in the microchannels where it is open at one end. The uniformity of the film thickness improved by increasing the negative pulse voltage because ions can arrive at the deeper part of the microchannel. In addition, the hardness increased as the depth of the coating position increased. This is because the radicals do not arrive at the deeper part of the microchannel, and the incident proportion of ions relative to that of radicals increases, resulting in a high hardness due to the amorphization of the film. The opening area of the microchannel where the aspect ratio is very small, radicals dominate the incident flux, whereas ions prevail over radicals above an aspect ratio of about 7.5. On the other hand, in the microchannels that are open at both ends, there were great improvements in uniformity of the film thickness, hardness, and the film structure. The a-C:H films were successfully deposited on the entire inner surface of a microchannel with an aspect ratio of 20.

  6. Alpha3* and alpha 7 nAChR-mediated Ca2+ transient generation in IMR-32 neuroblastoma cells.

    PubMed

    Ween, Hilde; Thorin-Hagene, Kirsten; Andersen, Elisabeth; Grønlien, Jens Halvard; Lee, Chih-Hung; Gopalakrishnan, Murali; Malysz, John

    2010-10-01

    Alpha3-containing (alpha 3*) and alpha 7 nicotinic acetylcholine receptors (nAChRs) are expressed in human IMR-32 neuroblastoma cells and implicated in Ca(2+) signaling. In this study, we investigated the intracellular Ca(2+) transient generation evoked by selective activation of alpha 3* (agonist potency rank order: epibatidine>varenicline>nicotine approximately cytisine) and alpha 7 (rank order in the presence of alpha 7 positive allosteric modulator or PAM: A-795723>NS6784 approximately PNU-282987) using, respectively, varenicline and NS6784 (+alpha 7 PAM) by Ca(2+) imaging. Effects of inhibitors of nAChRs (MLA and mecamylamine), ER Ca(2+) ATPase pump (CPA and thapsigargin), Ca(2+)-induced Ca(2+) release (ryanodine and dantrolene), Ca(2+) channels (nitrendipine, diltiazem, and Cd(2+)), and removal of extracellular Ca(2+) were examined. alpha 7 PAMs, when tested in the presence of NS6784, were more active when added first, followed by the agonist, than in the reverse order. Removal of extracellular Ca(2+) - but not CPA, thapsigargin, ryanodine, dantrolene, nitrendipine, diltiazem, or Cd(2+) - diminished the alpha 7 agonist-evoked Ca(2+) transients. In contrast, only diltiazem and nitrendipine and removal of extracellular Ca(2+) inhibited the alpha 3*-mediated Ca(2+) transients. The differential effect of diltiazem and nitrendipine versus Cd(2+) was due to direct inhibition of alpha 3* nAChRs as revealed by Ca(2+) imaging in HEK-293 cells expressing human alpha 3 beta 4 nAChRs and patch clamp in IMR-32 cells. In summary, this study provides evidence that alpha 3* and alpha 7 nAChR agonist-evoked global Ca(2+) transient generation in IMR-32 cells does not primarily involve voltage-dependent Ca(2+) channels, intracellular Ca(2+) stores, or Ca(2+)-induced Ca(2+) release. These mechanisms may, however, be still involved in other forms of nAChR-mediated Ca(2+) signaling.

  7. Enhanced synthesis and release of dopamine in transgenic mice with gain-of-function α6* nAChRs

    PubMed Central

    Wang, Yuexiang; Lee, Jang-Won; Oh, Gyeon; Grady, Sharon R.; McIntosh, J. Michael; Brunzell, Darlene H.; Cannon, Jason R.; Drenan, Ryan M.

    2014-01-01

    α6β2* nAChRs in the ventral tegmental area (VTA) to nucleus accumbens (NAc) pathway are implicated in the response to nicotine, and recent work suggests these receptors play a role in the rewarding action of ethanol. Here, we studied mice expressing gain-of-function α6β2* nAChRs (α6L9’S mice) that are hypersensitive to nicotine and endogenous acetylcholine (ACh). Evoked extracellular dopamine (DA) levels were enhanced in α6L9’S NAc slices compared to control, non-transgenic (nonTg) slices. Extracellular DA levels in both nonTg and α6L9’S slices were further enhanced in the presence of GBR12909, suggesting intact DA transporter function in both mouse strains. Ongoing α6β2* nAChR activation by ACh plays a role in enhancing DA levels, as α-conotoxin MII completely abolished evoked DA release in α6L9’S slices and decreased spontaneous DA release from striatal synaptosomes. In HPLC experiments, α6L9’S NAc tissue contained significantly more DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) compared to nonTg NAc tissue. Serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and norepinephrine (NE) were unchanged in α6L9’S compared to nonTg tissue. Western blot analysis revealed increased tyrosine hydroxylase expression in α6L9’S NAc. Overall, these results show that enhanced α6β2* nAChR activity in NAc can stimulate DA production and lead to increased extracellular DA levels. PMID:24266758

  8. NEWS: Solid foundations?

    NASA Astrophysics Data System (ADS)

    2000-07-01

    Among the initiatives to be found at UK universities is a vocational award with the title `University Foundation Degree' at Nottingham Trent University. This qualification will be offered in 14 different subjects including four in the Faculty of Science and Mathematics, in the areas of applied biology, applied sciences, chemistry and physics. The courses will be available on a two-year full-time, three-year sandwich or a part-time basis. Set at a higher standard and specification than the Higher National Diplomas which it replaces, the UFD has been devised in consultation with industry and will cover the technical and specialist areas demanded by employers to combat skills shortages. The UFD in applied sciences concentrates on practical applications through laboratory, IT and project work, supported by lectures and seminars. At the end students can enter the employment market or transfer onto the second year of a degree course. Science-based careers including research and development would be the aim of those taking the UFD in physics. The first year develops the fundamentals of modern physics supported by studies in mathematics, IT and computer programming, whilst year 2 is vocational in nature with industrial problem solving and work experience as well as an academic theme associated with environmental aspects of the subject. Those who complete the UFD will be allowed automatic progression to a specified honours degree course and would normally be expected to study for a further two years for this award. However, those demonstrating an outstanding academic performance can transfer to the linked degree programme at the end of the first year via fast-track modules. Back in May the UK's Quality Assurance Agency (QAA) announced new standard benchmarks for degrees. These will be introduced into higher education institutions from 2002 to outline the knowledge, understanding and skills a student should gain from a particular higher education course. These benchmark

  9. α7nAChR is expressed in satellite cells at different myogenic status during skeletal muscle wound healing in rats.

    PubMed

    Tian, Zhi-Ling; Jiang, Shu-Kun; Zhang, Miao; Wang, Meng; Li, Jiao-Yong; Zhao, Rui; Wang, Lin-Lin; Liu, Min; Li, Shan-Shan; Zhang, Meng-Zhou; Guan, Da-Wei

    2015-12-01

    Recent study has reported that α7 nicotine acetylcholine receptor (α7nAChR) is expressed in regenerated multinucleated myotubes. But the distribution of α7nAChR in satellite cells in different myogenic status is unknown. A preliminary study on the dynamic distribution of α7nAChR in satellite cells was performed by double indirect immunofluorescent procedures during skeletal muscle wound healing in rats. An animal model of skeletal muscle contusion was established in 40 Sprague-Dawley male rats. Samples were taken at 1, 3, 5, 7, 9, 13, 17 and 21 days after injury, respectively (five rats in each posttraumatic interval). Five rats were employed as control. In normal muscle specimens, weak immunoreactivity for α7nAChR was detected in a few satellite cells (considered as quiescent). α7nAChR-positive signals were observed in proliferated and differentiated satellite cells and regenerated multinucleated myotubes in the wounded areas. By morphometric analysis, the average number of α7nAChR+/Pax7+ and α7nAChR+/MyoD+ cells climaxed at 5 days post-injury. The average number of α7nAChR+/myogenin+ cells was significantly increased from 3 to 9 days post-injury as compared with other posttraumatic intervals. The protein level of α7nAChR maximized at 9 days post-injury, which implies that α7nAChR was associated with the satellite cells status. Our observations on expression of α7nAChR in satellite cells from quiescence to myotube formation suggest that α7nAChR may be involved in muscle regeneration by regulating satellite cell status.

  10. Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population

    PubMed Central

    Maeda, Yasuhiro; Migita, Kiyoshi; Higuchi, Osamu; Mukaino, Akihiro; Furukawa, Hiroshi; Komori, Atsumasa; Nakamura, Minoru; Hashimoto, Satoru; Nagaoka, Shinya; Abiru, Seigo; Yatsuhashi, Hiroshi; Matsuo, Hidenori; Kawakami, Atsushi; Yasunami, Michio; Nakane, Shunya

    2016-01-01

    Background/Aims Anti-ganglionic nicotinic acetylcholine receptor (gAChR) antibodies are observed in autoimmune diseases, as well as in patients with autoimmune autonomic ganglionopathy. However, the genetic background of anti-gAChR antibodies is unclear. Here, we investigated HLA alleles in autoimmune hepatitis (AIH) patients with or without anti-gAChR antibodies. Methodology/Principal Findings Genomic DNA from 260 patients with type-1 autoimmune hepatitis (AIH) were genotyped for HLA-A, B, DRB1, and DQB1 loci. Anti-gAChR antibodies in the sera form AIH patients were measured using the luciferase immunoprecipitation system, and examined allelic association in patients with or without anti-gAChR antibodies. Methodology/ Methods We detected anti-α3 or -β4 gAChR antibodies in 11.5% (30/260) of patients with AIH. Among AIH patients there was no significant association between HLA-A, B DQB1 alleles and the positivity for anti-gAChR antibodies. Whereas the HLA-DRB1*0403 allele showed a significantly increased frequency in AIH patients with anti-gAChR antibodies compared with those without anti-gAChR antibodies. Conclusions/Significance The frequency of the HLA-DRB1*0403 allele differed among Japanese patients with AIH according to the presence or absence of anti-gAChR antibodies. Our findings suggest that particular HLA class II molecules might control the development of anti-gAChR antibodies in the autoimmune response to gAChR. PMID:26807576

  11. Differential Cytokine Changes in Patients with Myasthenia Gravis with Antibodies against AChR and MuSK

    PubMed Central

    Yilmaz, Vuslat; Oflazer, Piraye; Aysal, Fikret; Durmus, Hacer; Poulas, Kostas; Yentur, Sibel P.; Gulsen-Parman, Yesim; Tzartos, Socrates; Marx, Alexander; Tuzun, Erdem; Deymeer, Feza; Saruhan-Direskeneli, Güher

    2015-01-01

    Neuromuscular transmission failure in myasthenia gravis (MG) is most commonly elicited by autoantibodies (ab) to the acetylcholine receptor or the muscle-specific kinase, constituting AChR-MG and MuSK-MG. It is controversial whether these MG subtypes arise through different T helper (Th) 1, Th2 or Th17 polarized immune reactions and how these reactions are blunted by immunosuppression. To address these questions, plasma levels of cytokines related to various Th subtypes were determined in patients with AChR-MG, MuSK-MG and healthy controls (CON). Peripheral blood mononuclear cells (PBMC) were activated in vitro by anti-CD3, and cytokines were quantified in supernatants. In purified blood CD4+ T cells, RNA of various cytokines, Th subtype specific transcription factors and the co-stimulatory molecule, CD40L, were quantified by qRT-PCR. Plasma levels of Th1, Th2 and Th17 related cytokines were overall not significantly different between MG subtypes and CON. By contrast, in vitro stimulated PBMC from MuSK-MG but not AChR-MG patients showed significantly increased secretion of the Th1, Th17 and T follicular helper cell related cytokines, IFN-γ, IL-17A and IL-21. Stimulated expression of IL-4, IL-6, IL-10 and IL-13 was not significantly different. At the RNA level, expression of CD40L by CD4+ T cells was reduced in both AChR-MG and MuSK-MG patients while expression of Th subset related cytokines and transcription factors were normal. Immunosuppression treatment had two effects: First, it reduced levels of IL12p40 in the plasma of AChR-MG and MuSK-MG patients, leaving other cytokine levels unchanged; second, it reduced spontaneous secretion of IFN-γ and increased secretion of IL-6 and IL-10 by cultured PBMC from AChR-MG, but not MuSK-MG patients. We conclude that Th1 and Th17 immune reactions play a role in MuSK-MG. Immunosuppression attenuates the Th1 response in AChR-MG and MuSK-MG, but otherwise modulates immune responses in AChR-MG and MuSK-MG patients

  12. Polish Foundation for Energy Efficiency

    SciTech Connect

    1995-12-31

    The Polish Foundation for Energy Efficiency (FEWE) was established in Poland at the end of 1990. FEWE, as an independent and non-profit organization, has the following objectives: to strive towards an energy efficient national economy, and to show the way and methods by use of which energy efficiency can be increased. The activity of the Foundation covers the entire territory of Poland through three regional centers: in Warsaw, Katowice and Cracow. FEWE employs well-known and experienced specialists within thermal and power engineering, civil engineering, economy and applied sciences. The organizer of the Foundation has been Battelle Memorial Institute - Pacific Northwest Laboratories from the USA.

  13. Willis-Ekbom Disease Foundation

    MedlinePlus

    ... specialist through the RLS Foundation website. After a sleep study, we learned that I have restless legs syndrome, just like my grandfather. With treatment I can sleep again. I avoid triggers and my grades are ...

  14. Crohn's & Colitis Foundation of America

    MedlinePlus

    ... enabled to enjoy the full interactive experience. Crohn's & Colitis Foundation of America Find a Doctor Find a ... Local Chapters News Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis ...

  15. Foundation for Film and Science

    ERIC Educational Resources Information Center

    van der Veen, G.

    1976-01-01

    Provides a comprehensive discussion on the Stichting Film en Wetenschap, SFW (Foundation for Film and Science), in Utrecht. Various aspects of the use of audio-visual aids in university teaching are looked at in detail. (Editor/RK)

  16. Influence of wind turbine foundation

    NASA Technical Reports Server (NTRS)

    Yee, S. T.

    1978-01-01

    The 200 kW Mod-0A wind turbine was modeled using a 3 lumped mass-spring system for the superstructure and a rotational spring for the foundation and supporting soil. Natural frequencies were calculated using soil elastic moduli varying from 3000 to 22,400 p.s.i. The reduction in natural frequencies from the rigid foundation case ranged up to 20 percent.

  17. Vagus nerve stimulation mediates protection from kidney ischemia-reperfusion injury through α7nAChR+ splenocytes

    PubMed Central

    Inoue, Tsuyoshi; Abe, Chikara; Sung, Sun-sang J.; Moscalu, Stefan; Jankowski, Jakub; Huang, Liping; Ye, Hong; Guyenet, Patrice G.

    2016-01-01

    The nervous and immune systems interact in complex ways to maintain homeostasis and respond to stress or injury, and rapid nerve conduction can provide instantaneous input for modulating inflammation. The inflammatory reflex referred to as the cholinergic antiinflammatory pathway regulates innate and adaptive immunity, and modulation of this reflex by vagus nerve stimulation (VNS) is effective in various inflammatory disease models, such as rheumatoid arthritis and inflammatory bowel disease. Effectiveness of VNS in these models necessitates the integration of neural signals and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. Here, we sought to determine whether electrical stimulation of the vagus nerve attenuates kidney ischemia-reperfusion injury (IRI), which promotes the release of proinflammatory molecules. Stimulation of vagal afferents or efferents in mice 24 hours before IRI markedly attenuated acute kidney injury (AKI) and decreased plasma TNF. Furthermore, this protection was abolished in animals in which splenectomy was performed 7 days before VNS and IRI. In mice lacking α7nAChR, prior VNS did not prevent IRI. Conversely, adoptive transfer of VNS-conditioned α7nAChR splenocytes conferred protection to recipient mice subjected to IRI. Together, these results demonstrate that VNS-mediated attenuation of AKI and systemic inflammation depends on α7nAChR-positive splenocytes. PMID:27088805

  18. Effect of nicotinic acetylcholine receptor alpha 1 (nAChRα1) peptides on rabies virus infection in neuronal cells.

    PubMed

    Sajjanar, Basavaraj; Saxena, Shikha; Bisht, Deepika; Singh, Arvind Kumar; Manjunatha Reddy, G B; Singh, Rajendra; Singh, R P; Kumar, Satish

    2016-06-01

    Rabies virus (RABV) is neurotropic and causes acute progressive encephalitis. Herein, we report the interaction of nAChRα1-subunit peptides with RABV and the effect of these peptides on RABV infection in cultured neuronal cells. Peptide sequences derived from torpedo, bovine, human and rats were synthesized and studied for their interactions with RABV using virus capture ELISA and peptide immunofluorescence. The results showed specific binding of the nAChRα1-subunit peptides to the RABV. In the virus adsorption assay, these peptides were found to inhibit the attachment of the RABV to the neuronal cells. The nAChRα1-subunit peptides inhibited the RABV infection and reduced viral gene expression in the cultured neuroblastoma (N2A) cells. Torpedo peptide sequence (T-32) had highest antiviral effect (IC50=14±3.01μM) compared to the other peptides studied. The results of the study indicated that nAChRα1-subunit peptides may act as receptor decoy molecules and inhibit the binding of virus to the native host cell receptors and hence may reduce viral infection. PMID:26656837

  19. R86Q, a mutation in BmAChE3 yielding a Rhipicephalus microplus organophosphate-insensitive acetylcholinesterase

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutations were identified in the sequence encoding the acetylcholinesterase, BmAChE3, in strains of Rhipicephalus (Boophilus) microplus (Canestrini) resistant or susceptible to orgaonphosphorus acaricide. The mutation which appeared most frequently in the organophosphorus-resistant San Román strain...

  20. Myopathic changes detected by quantitative electromyography in patients with MuSK and AChR positive myasthenia gravis.

    PubMed

    Nikolic, Ana; Basta, Ivana; Stojanovic, Vidosava Rakocevic; Stevic, Zorica; Peric, Stojan; Lavrnic, Dragana

    2016-05-01

    Myopathic changes are frequent a electrophysiological finding in patients with muscle specific tyrosine kinase (MuSK) positive myasthenia gravis (MG). The aim of this study was to explore the importance of quantitative electromyography (EMG) in the detection of myopathic changes in MuSK MG patients. Classical and quantitative EMG were performed in 31 MuSK and 28 acetylcholine receptor (AChR) positive MG patients, matched by sex, age, disease duration and severity. Classical EMG revealed the presence of myopathic changes more frequently in MuSK MG compared to AChR MG patients, especially in the facial muscles. Quantitative EMG registered myopathic lesions more frequently than classical EMG, but the frequency was similar between MuSK and AChR MG patients. Quantitative EMG revealed myopathic changes in the majority of both MuSK and AChR positive MG patients. This examination is sensitive, but it cannot be used to differentiate between MG patients belonging to the different disease groups. It should not be used in isolation. Rather, it should complement classical EMG in the detection of myopathic changes.

  1. Geological Mapping of the Ac-H-9 Occator Quadrangle of Ceres from NASA Dawn Mission

    NASA Astrophysics Data System (ADS)

    Buczkowski, Debra; Williams, David; Scully, Jennifer; Mest, Scott; Crown, David; Aileen Yingst, R.; Schenk, Paul; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Platz, Thomas; Nathues, Andreas; Hoffmann, Martin; Schaefer, Michael; Marchi, Simone; De Sanctis, M. Cristina; Raymond, Carol; Russell, Chris

    2016-04-01

    As was done at Vesta [1], the Dawn Science Team is conducting a geological mapping cam-paign at Ceres during the nominal mission, including iterative mapping using data obtained dur-ing each orbital phase. We are using geological mapping as a method to identify the geologic processes that have modified the surface of dwarf planet Ceres. We here present the geology of the Ac-H-9 Occator quadrangle, located between 22°S-22°N and 216-288°E. The Ac-H-9 map area is completely within the topographically high region on Ceres named Erntedank Planum. It is one of two longitudinally distinct regions where ESA Herschel space telescope data suggested a release of water vapor [2]. The quadrangle includes several other notable features, including those discussed below. Occator is the 92 km diameter crater that hosts the "Bright Spot 5" that was identified in Hubble Space Telescope data [3], which is actually comprised of multiple bright spots on the crater floor. The floor of Occator is cut by linear fractures, while circumferential fractures are found in the ejecta and on the crater walls. The bright spots are noticeably associated with the floor fractures, although the brightest spot is associated with a central pit [4]. Multiple lobate flows are observed on the crater floor; these appear to be sourced from the center of the crater. The crater has a scalloped rim that is cut by regional linear structures, displaying a cross-section of one structure in the crater wall. Color data show that the Occator ejecta have multiple colors, generally related to changes in morphology. Azacca is a 50 km diameter crater that has a central peak and bright spots on its floor and within its ejecta. Like Occator, Azacca has both floor fractures and circumferential fractures in its ejecta and crater walls. Also like Occator, the Azacca ejecta is multi-colored with variable morphology. Linear structures - including grooves, pit crater chains, fractures and troughs - cross much of the eastern

  2. Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

    NASA Technical Reports Server (NTRS)

    Schrage, William G.; Woodman, Christopher R.; Laughlin, M. Harold

    2002-01-01

    The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

  3. A behaviorological thanatology: Foundations and implications

    PubMed Central

    Fraley, Lawrence E.

    1998-01-01

    Foundation principles supporting a behaviorological thanatology are reviewed, including concepts of life, person, death, value, right, ethic, and body/person distinctions. These natural science foundations are contrasted with traditional foundations, and their respective implications are speculatively explored. PMID:22478293

  4. A behaviorological thanatology: Foundations and implications.

    PubMed

    Fraley, L E

    1998-01-01

    Foundation principles supporting a behaviorological thanatology are reviewed, including concepts of life, person, death, value, right, ethic, and body/person distinctions. These natural science foundations are contrasted with traditional foundations, and their respective implications are speculatively explored.

  5. Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

    SciTech Connect

    McPherson, D.W.; Luo, H.; Knapp, F.F. Jr.

    1994-06-01

    Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

  6. Inhibition of ACh release at an Aplysia synapse by neurotoxic phospholipases A2: specific receptors and mechanisms of action.

    PubMed Central

    Fossier, P; Lambeau, G; Lazdunski, M; Baux, G

    1995-01-01

    1. Monochain (OS2) and multichain (taipoxin) neurotoxic phospholipases A2 (PLA2), purified from taipan snake venom, both inhibited ACh release at a concentration of 20 nM (90% inhibition in 2 h) at an identified synapse from buccal ganglion of Aplysia californica. 2. The Na+ current was unchanged upon application of either OS2 or taipoxin. Conversely, presynaptic K+ currents (IA and IK) were increased by taipoxin but not by OS2. In addition, OS2 induced a significant decrease of the presynaptic Ca2+ current (30%) while taipoxin increased this latter current by 20-30%. 3. Bee venom PLA2, another monochain neurotoxic PLA2, also inhibited ACh release while non-toxic enzymatically active PLA2s like OS1 (also purified from taipan snake venom) or porcine pancreatic PLA2 elicited a much weaker inhibition of ACh release, suggesting a specific action of neurotoxic PLA2s versus non-toxic PLA2s on ACh release. 4. Using iodinated OS2, specific high affinity binding sites with molecular masses of 140 and 18 kDa have been identified on Aplysia ganglia. The maximal binding capacities were 55 and 300-400 fmol (mg protein)-1 for membrane preparations from whole and buccal ganglia, respectively. These binding sites are of high affinity for neurotoxic PLA2s (Kd values, 100-800 pM) and of very low affinity for non-toxic PLA2s (Kd values in the micromolar range), thus indicating that these binding sites are presumably involved in the blockade of ACh release by neurotoxic PLA2s. Images Figure 8 Figure 9 PMID:8583413

  7. Continuing Education in the Era of Quantum Change. 2003 ACHE Proceedings. (65th Annual Meeting, Charlottesville, VA, November 8-12, 2003)

    ERIC Educational Resources Information Center

    Barrineau, Irene T., Ed.

    2003-01-01

    This document presents the proceedings of the 2003 annual meeting of the Association for Continuing Higher Education (ACHE). These proceedings record the 65th Annual Meeting of ACHE held in Charlottesville, Virginia. President Allen Varner's theme for this annual meeting was, "Continuing Education in the Era of Quantum Change." The theme was…

  8. Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.

    PubMed

    Kouvatsos, Nikolaos; Giastas, Petros; Chroni-Tzartou, Dafni; Poulopoulou, Cornelia; Tzartos, Socrates J

    2016-08-23

    In this study we report the X-ray crystal structure of the extracellular domain (ECD) of the human neuronal α2 nicotinic acetylcholine receptor (nAChR) subunit in complex with the agonist epibatidine at 3.2 Å. Interestingly, α2 was crystallized as a pentamer, revealing the intersubunit interactions in a wild type neuronal nAChR ECD and the full ligand binding pocket conferred by two adjacent α subunits. The pentameric assembly presents the conserved structural scaffold observed in homologous proteins, as well as distinctive features, providing unique structural information of the binding site between principal and complementary faces. Structure-guided mutagenesis and electrophysiological data confirmed the presence of the α2(+)/α2(-) binding site on the heteromeric low sensitivity α2β2 nAChR and validated the functional importance of specific residues in α2 and β2 nAChR subunits. Given the pathological importance of the α2 nAChR subunit and the high sequence identity with α4 (78%) and other neuronal nAChR subunits, our findings offer valuable information for modeling several nAChRs and ultimately for structure-based design of subtype specific drugs against the nAChR associated diseases. PMID:27493220

  9. Surface-Wave Plasma Deposition of a-C:H Films for Field Emission

    NASA Astrophysics Data System (ADS)

    Sano, Toru; Nagatsu, Masaaki; Takada, Noriharu; Toyoda, Hirotaka; Sugai, Hideo; Guang, W. X.; Hirao, Takashi; Toyoda, Naoki

    2000-10-01

    Recently crystalline diamond or diamondlike carbon (DLC) thin films prepared by the plasma enhanced CVD techniques have been widely studied as a new material of electron emitter for the next generation large-area field emission display. Among them, DLC films grown at low temperature are more attractive from an aspect of industrial manufacturing. In this study, we have carried out the deposition of hydrogenated amorphous carbon(a-C:H) films using a high density, low pressure surface-wave plasma (SWP). The SWP was produced in a 40cm-diameter vacuum chamber by introducing 2.45 GHz microwave through a quartz window via slot antennas. The a-C:H films were deposited on a silicon substrate immersed in He/CH4 plasma, under discharge conditions of 700 W microwave power and 200 mTorr total pressure. Excellent field emission characteristics were obtained: the threshold electric field defined at an emission current density of 1 μA/cm^2 was obtained to be 4 V/μm. Other film characteristics measured with the XPS and FT-IR are also presented. This work was supported by a Grant-in-Aid for Science Research from the Ministry of Education, Science, Sports and Culture in Japan.

  10. Biocompatible Silver-containing a-C:H and a-C coatings: AComparative Study

    SciTech Connect

    Endrino, Jose Luis; Allen, Matthew; Escobar Galindo, Ramon; Zhang, Hanshen; Anders, Andre; Albella, Jose Maria

    2007-04-01

    Hydrogenated diamond-like-carbon (a-C:H) and hydrogen-free amorphous carbon (a-C) coatings are known to be biocompatible and have good chemical inertness. For this reason, both of these materials are strong candidates to be used as a matrix that embeds metallic elements with antimicrobial effect. In this comparative study, we have incorporated silver into diamond-like carbon (DLC) coatings by plasma based ion implantation and deposition (PBII&D) using methane (CH4) plasma and simultaneously depositing Ag from a pulsed cathodic arc source. In addition, we have grown amorphous carbon - silver composite coatings using a dual-cathode pulsed filtered cathodic-arc (FCA) source. The silver atomic content of the deposited samples was analyzed using glow discharge optical spectroscopy (GDOES). In both cases, the arc pulse frequency of the silver cathode was adjusted in order to obtain samples with approximately 5 at.% of Ag. Surface hardness of the deposited films was analyzed using the nanoindentation technique. Cell viability for both a-C:H/Ag and a-C:/Ag samples deposited on 24-well tissue culture plates has been evaluated.

  11. Adsorption of alcohols and fatty acids onto hydrogenated (a-C:H) DLC coatings

    NASA Astrophysics Data System (ADS)

    Simič, R.; Kalin, M.; Kovač, J.; Jakša, G.

    2016-02-01

    Information about the interactions between lubricants and DLC coatings is scarce, despite there having been many studies over the years. In this investigation we used ToF-SIMS, XPS and contact-angle analyses to examine the adsorption ability and mechanisms with respect to two oiliness additives, i.e., hexadecanol and hexadecanoic acid, on an a-C:H coating. In addition, we analyzed the resistance of the adsorbed films to external influences like solvent cleaning. The results show that both molecules adsorb onto surface oxides and hydroxides present on the initial DLC surface and shield these structures with their hydrocarbon tails. This makes the surfaces less polar, which is manifested in a smaller polar component of the surface energy. We also showed that ultrasonic cleaning in heptane has no significant effect on the quantity of adsorbed molecules or on their chemical state. This not only shows the relatively strong adsorption of these molecules, but also provides useful information for future experimental work. Of the two examined molecules, the acid showed a greater adsorption ability than the alcohol, which explains some of the previously reported better tribological properties in the case of the acid with respect to the alcohol.

  12. Conotoxin Interactions with α9α10-nAChRs: Is the α9α10-Nicotinic Acetylcholine Receptor an Important Therapeutic Target for Pain Management?

    PubMed Central

    Mohammadi, Sarasa A.; Christie, MacDonald J.

    2015-01-01

    The α9α10-nicotinic acetylcholine receptor (nAChR) has been implicated in pain and has been proposed to be a novel target for analgesics. However, the evidence to support the involvement of the α9α10-nAChR in pain is conflicted. This receptor was first implicated in pain with the characterisation of conotoxin Vc1.1, which is highly selective for α9α10-nAChRs and is an efficacious analgesic in chronic pain models with restorative capacities and no reported side effects. Numerous other analgesic conotoxin and non-conotoxin molecules have been subsequently characterised that also inhibit α9α10-nAChRs. However, there is evidence that α9α10-nAChR inhibition is neither necessary nor sufficient for analgesia. α9α10-nAChR-inhibiting analogues of Vc1.1 have no analgesic effects. Genetically-modified α9-nAChR knockout mice have a phenotype that is markedly different from the analgesic profile of Vc1.1 and similar conotoxins, suggesting that the conotoxin effects are largely independent of α9α10-nAChRs. Furthermore, an alternative mechanism of analgesia by Vc1.1 and other similar conotoxins involving non-canonical coupling of GABAB receptors to voltage-gated calcium channels is known. Additional incongruities regarding α9α10-nAChRs in analgesia are discussed. A more comprehensive characterisation of the role of α9α10-nAChRs in pain is crucial for understanding the analgesic action of conotoxins and for improved drug design. PMID:26426047

  13. Foundation + Collaboration + Inspiration. The Joyce Foundation 2009 Annual Report

    ERIC Educational Resources Information Center

    Joyce Foundation, 2010

    2010-01-01

    Among the great strengths of a policy-oriented foundation like Joyce is the willingness to take a long view, to be patient investors in ideas that take time to have impact, and to take chances on projects that may not work out. But in times of crisis, Joyce team and partners also have an obligation to be responsive to immediate challenges in their…

  14. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Choi, Junho

    2015-08-01

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from -1.0 to -15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation

  15. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    SciTech Connect

    Hirata, Yuki; Choi, Junho

    2015-08-28

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a

  16. Pavlov and the Rockefeller Foundation.

    PubMed

    Windholz, G; Kuppers, J R

    1988-01-01

    Despite the tension between the United States and the Soviet Union in the early 1920's, the Rockefeller Foundation and the Rockefeller Institute for Medical Research found ways to assist I.P. Pavlov. In addition to providing scientific literature and financial aid, these institutions and their officers rendered important moral support to the scientific career of Pavlov during his later years. In 1923, as a guest of the Rockefeller Institute, Pavlov visited American scientific laboratories. In 1924, he requested and received a number of books on physiology, and during the 1930's the Foundation helped him to acquire equipment for his Leningrad laboratory.

  17. Raising Money Through an Institutionally Related Foundation.

    ERIC Educational Resources Information Center

    Reilley, Timothy A., Ed.

    The creation of foundations for fund raising at public colleges and new ideas and techniques for established foundations are discussed in 13 chapters. The relationship of the foundation and the institution is described from the viewpoint of the institution and also that of the foundation. Article titles and authors include: "How the Foundation…

  18. But…What about My Epistemological Foundations?

    ERIC Educational Resources Information Center

    Curin, Raquel Isabel Barrera

    2015-01-01

    At one time or another, all researchers in mathematics education must face the rather complex question of their epistemological foundations. Discussing epistemological foundations naturally leads to a conversation about theories. Theories and epistemological foundations work in a circular fashion: theories can have epistemological foundations and…

  19. Geological Mapping of the Ac-H-12 Toharu Quadrangle of Ceres from NASA Dawn Mission

    NASA Astrophysics Data System (ADS)

    Mest, Scott; Williams, David; Crown, David; Yingst, Aileen; Buczkowski, Debra; Scully, Jennifer; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Nathues, Andres; Hoffmann, Martin; Schaefer, Michael; Raymond, Carol; Russell, Christopher

    2016-04-01

    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the surface geology and geologic evolution of the Ac-H-12 Toharu Quadrangle (21-66°S, 90-180°E). At the time of this writing LAMO images (35 m/pixel) are just becoming available. The current geologic map of Ac-H-12 was produced using ArcGIS software, and is based on HAMO images (140 m/pixel) and Survey (400 m/pixel) digital terrain models (for topographic information). Dawn Framing Camera (FC) color images were also used to provide context for map unit identification. The map (to be presented as a poster) will be updated from analyses of LAMO images. The Toharu Quadrangle is named after crater Toharu (86 km diameter; 48.3°S, 156°E), and is dominated by smooth terrain in the north, and more heavily cratered terrain in the south. The quad exhibits ~9 km of relief, with the highest elevations (~3.5-4.6 km) found among the western plateau and eastern crater rims, and the lowest elevation found on the floor of crater Chaminuka. Preliminary geologic mapping has defined three regional units (smooth material, smooth Kerwan floor material, and cratered terrain) that dominate the quadrangle, as well as a series of impact crater material units. Smooth materials form nearly flat-lying plains in the northwest part of the quad, and overlies hummocky materials in some areas. These smooth materials extend over a much broader area outside of the quad, and appear to contain some of the lowest crater densities on Ceres. Cratered terrain forms much of the map area and contains rugged surfaces formed largely by the structures and deposits of impact features. In addition to geologic units, a number of geologic features - including crater rims, furrows, scarps, troughs, and impact

  20. Toxicity and mAChRs binding activity of Cassiopea xamachana venom from Puerto Rican coasts.

    PubMed

    Radwan, Faisal F Y; Román, Laura G; Baksi, Krishna; Burnett, Joseph W

    2005-01-01

    A separation of toxic components from the upside down jellyfish Cassiopea xamachana (Cx) was carried out to study their cytotoxic effects and examine whether these effects are combined with a binding activity to cell membrane receptors. Nematocysts containing toxins were isolated from the autolysed tentacles, ruptured by sonication, and the crude venom (CxTX) was separated from the pellets by ultracentrifugation. For identifying its bioactive components, CxTX was fractionated by gel filtration chromatography into six fractions (named fraction I-VI). The toxicity of CxTX and fractions was tested on mice; however, the hemolytic activity was tested on saline washed human erythrocytes. The LD50 of CxTX was 0.75 microg/g of mouse body and for fraction III, IV and VI were 0.28, 0.25 and 0.12 microg/g, respectively. Fractions I, II and V were not lethal at doses equivalent to LD50 1 microg/g. The hemolytic and phospholipase A2 (PLA2) activities of most fractions were well correlated with their mice toxicity. However, fraction VI, which contains the low molecular mass protein components (< or =10 kDa), has shown no PLA2 activity but highest toxicity to mice, highest hemolytic activity, and bound significantly to the acetylcholine muscarinic receptors (mAChRs) isolated from rat brain. The results suggested that fraction VI contains proteinaceous components contributing to most of cytolysis as well as membrane binding events. Meanwhile, fraction IV has shown high PLA2 that may contribute to the venom lethality and paralytic effects. PMID:15581689

  1. Heritability and Fitness Correlates of Personality in the Ache, a Natural-Fertility Population in Paraguay

    PubMed Central

    Bailey, Drew H.; Walker, Robert S.; Blomquist, Gregory E.; Hill, Kim R.; Hurtado, A. Magdalena; Geary, David C.

    2013-01-01

    The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality. PMID:23527163

  2. Heritability and fitness correlates of personality in the Ache, a natural-fertility population in Paraguay.

    PubMed

    Bailey, Drew H; Walker, Robert S; Blomquist, Gregory E; Hill, Kim R; Hurtado, A Magdalena; Geary, David C

    2013-01-01

    The current study assessed the heritability of personality in a traditional natural-fertility population, the Ache of eastern Paraguay. Self-reports (n = 110) and other-reports (n = 66) on the commonly used Big Five Personality Inventory (i.e., extraversion, agreeableness, conscientiousness, neuroticism, openness) were collected. Self-reports did not support the Five Factor Model developed with Western samples, and did not correlate with other-reports for three of the five measured personality factors. Heritability was assessed using factors that were consistent across self- and other-reports and factors assessed using other-reports that showed reliabilities similar to those found in Western samples. Analyses of these items in combination with a multi-generation pedigree (n = 2,132) revealed heritability estimates similar to those found in most Western samples, although we were not able to separately estimate the influence of the common environment on these traits. We also assessed relations between personality and reproductive success (RS), allowing for a test of several mechanisms that might be maintaining heritable variation in personality. Phenotypic analyses, based largely on other-reports, revealed that extraverted men had higher RS than other men, but no other dimensions of personality predicted RS in either sex. Mothers with more agreeable children had more children, and parents mated assortatively on personality. Of the evolutionary processes proposed to maintain variation in personality, assortative mating, selective neutrality, and temporal variation in selection pressures received the most support. However, the current study does not rule out other processes affecting the evolution and maintenance of individual differences in human personality.

  3. Haemocompatibility of hydrogenated amorphous carbon (a-C:H) films synthesized by plasma immersion ion implantation-deposition

    NASA Astrophysics Data System (ADS)

    Yang, P.; Kwok, S. C. H.; Chu, P. K.; Leng, Y. X.; Chen, J. Y.; Wang, J.; Huang, N.

    2003-05-01

    Diamond-like-carbon has attracted much attention recently as a potential biomaterial in blood contacting biomedical devices. However, previous reports in this area have not adequately addressed the biocompatibility and acceptability of the materials in blood contacting applications. In this study, hydrogenated amorphous carbon (a-C:H) films were fabricated on silicon wafers (1 0 0) using plasma immersion ion implantation-deposition. A series of a-C:H films with different structures and chemical bonds were fabricated under different substrate voltages. The results indicate that film graphitization is promoted at higher substrate bias. The film deposited at a lower substrate bias of -75 V possesses better blood compatibility than the films at higher bias and stainless steel. Our results suggest two possible paths to improve the blood compatibility, suppression of the endogenic clotting system and reduction of platelet activation.

  4. Automated Patch Clamp Analysis of nAChα7 and Na(V)1.7 Channels.

    PubMed

    Obergrussberger, Alison; Haarmann, Claudia; Rinke, Ilka; Becker, Nadine; Guinot, David; Brueggemann, Andrea; Stoelzle-Feix, Sonja; George, Michael; Fertig, Niels

    2014-01-01

    Automated patch clamp devices are now commonly used for studying ion channels. A useful modification of this approach is the replacement of the glass pipet with a thin planar glass layer with a small hole in the middle. Planar patch clamp devices, such as the three described in this unit, are overtaking glass pipets in popularity because they increase throughput, are easier to use, provide for the acquisition of high-quality and information-rich data, and allow for rapid perfusion and temperature control. Covered in this unit are two challenging targets in drug discovery: voltage-gated sodium subtype 1.7 (Na(V)1.7) and nicotinic acetylcholine α7 receptors (nAChα7R). Provided herein are protocols for recording activation and inactivation kinetics of Na(V)1.7, and activation and allosteric modulation of nAChα7R. PMID:24934604

  5. Foundations of Responsibility for Children

    ERIC Educational Resources Information Center

    Dillen, Annemie

    2008-01-01

    Children's vulnerability asks for people taking up responsibility for children. In this contribution, three different ways of thinking on foundations of (ethical and spiritual) responsibility for children are discussed, namely, a liberalist, a social-constructivist and a naturalist paradigm. The author argues that cultural and natural elements are…

  6. Principles for Foundations of Education.

    ERIC Educational Resources Information Center

    Britt, John

    The significance of the foundations of education approach to teaching is apparent in the ideas of John Henry Newman, Karl Jaspers, Jose Ortega y Gasset, and Mortimer Adler. Newman maintained that there is a circle of knowledge and once this unity is ignored the result is distortion in the learners and in the knowledge. To retain the whole, the…

  7. Building Trades. Block II. Foundations.

    ERIC Educational Resources Information Center

    Texas A and M Univ., College Station. Vocational Instructional Services.

    Twelve informational lessons and eleven manipulative lessons are provided on foundations as applied to the building trades. Informational lessons cover land measurements; blueprint reading; level instruments; building and site planning; building site preparation; laying out building lines; soil preparation and special evacuation; concrete forms;…

  8. Soils and Foundations: A Syllabus.

    ERIC Educational Resources Information Center

    Long, Melvin J.

    The teaching guide and course outline for a 12-week course in soils and foundations is designed to help student technicians in a two-year associate degree civil engineering technology program to obtain entry level employment as highway engineering aides, soil testing technicians, soil mappers, or construction inspectors. The seven teaching units…

  9. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  10. Epistemological Foundations of School Science.

    ERIC Educational Resources Information Center

    Izquierdo-Aymerich, Merce; Aduriz-Bravo, Agustin

    2003-01-01

    Presents a theoretical framework that provides foundations for school science and defines some research problems. Begins with what is already known about students' models and cognition in order to construct proposals of didactical intervention. Proposes an analogous model for school science in which experimentation and language play the key roles.…

  11. Effect of calcium on nicotine-induced current expressed by an atypical alpha-bungarotoxin-insensitive nAChR2.

    PubMed

    Thany, Steeve H; Courjaret, Raphael; Lapied, Bruno

    2008-06-27

    Two distinct native alpha-bungarotoxin (alpha-Bgt)-insensitive nicotinic acetylcholine receptors (nAChRs), named nAChR1 and nAChR2, were identified in the cockroach Periplaneta americana dorsal unpaired median (DUM) neurons. They differed in their electrophysiological, pharmacological properties and intracellular regulation pathways. nAChR2 being an atypical nicotinic receptor closed upon agonist application and its current-voltage relationship resulted from a reduction in potassium conductance. In this study, using whole-cell patch-clamp technique, we demonstrated that calcium modulated nAChR2-mediated nicotine response. Under 0.5 microM alpha-Bgt and 20 mM d-tubocurarine, the nicotine-induced inward current amplitude was strongly reduced in the presence of intracellularly applied BAPTA or bath application of calcium-free solution. In addition, using cadmium chloride, we showed that nicotine response was modulated by extracellular calcium through plasma membrane calcium channels. Moreover, extracellular application of caffeine and thapsigargin reduced nAChR2-mediated response. Together these experiments revealed a complex calcium-dependent regulation of nAChR2. PMID:18485593

  12. Effects of a7nAChR agonist on the tissue estrogen receptor expression of castrated rats

    PubMed Central

    Ma, Feng; Gong, Fan; Lv, Jinhan; Gao, Jun; Ma, Jingzu

    2015-01-01

    Osteoporosis is one common disease in postmenopausal women due to depressed estrogen level. It has been known that inflammatory factors are involved in osteoporosis pathogenesis. One regulator of inflammatory cascade reaction, a7-nicotinic acetylcholine receptor (a7nAChR), therefore, may exert certain role in osteoporosis. This study thus investigated this question on an osteoporosis rat model after castration. Rats were firstly castrated to induce osteoporosis, and then received a7nAChR agonist (PNU-282987), diethylstilbestrol or saline via intraperitoneal injection. After 6 or 12 weeks, bone samples were collected for counting osteoblast number, bone density and estrogen receptor (ERα and ERβ) expression, in addition to the serum laboratory of inflammatory factors. Bone density, osteoclast number, ERα and ERβ expression level were significantly depressed in model group, and were remarkable potentiated in the drug treatment group (P<0.05). The levels of BGP and PTH in drug treatment group were decreased compared to diethylstilbestrol group, while E2 and IGF-1 showed up-regulation. Agonist of a7nAChR can up-regulate estrogen receptor expression and may prevent the occurrence and development of osteoporosis. PMID:26722551

  13. Endogenously released ACh and exogenous nicotine differentially facilitate long-term potentiation induction in the hippocampal CA1 region of mice.

    PubMed

    Nakauchi, Sakura; Sumikawa, Katumi

    2012-05-01

    We examined the role of α7- and β2-containing nicotinic acetylcholine receptors (nAChRs) in the induction of long-term potentiation (LTP). Theta-burst stimulation (TBS), mimicking the brain's naturally occurring theta rhythm, induced robust LTP in hippocampal slices from α7 and β2 knockout mice. This suggests TBS is capable of inducing LTP without activation of α7- or β2-containing nAChRs. However, when weak TBS was applied, the modulatory effects of nicotinic receptors on LTP induction became visible. We showed that during weak TBS, activation of α7 nAChRs occurs by the release of ACh, contributing to LTP induction. Additionally, bath-application of nicotine activated β2-containing nAChRs to promote LTP induction. Despite predicted nicotine-induced desensitization, synaptically mediated activation of α7 nAChRs still occurs in the presence of nicotine and contributed to LTP induction. Optical recording of single-stimulation-evoked excitatory activity with a voltage-sensitive dye revealed enhanced excitatory activity in the presence of nicotine. This effect of nicotine was robust during high-frequency stimulation, and was accompanied by enhanced burst excitatory postsynaptic potentials. Nicotine-induced enhancement of excitatory activity was observed in slices from α7 knockout mice, but was absent in β2 knockout mice. These results suggest that the nicotine-induced enhancement of excitatory activity is mediated by β2-containing nAChRs, and is related to the nicotine-induced facilitation of LTP induction. Thus, our study demonstrates that the activation of α7- and β2-containing nAChRs differentially facilitates LTP induction via endogenously released ACh and exogenous nicotine, respectively, in the hippocampal CA1 region of mice.

  14. Contribution of α4β2 nAChR in nicotine-induced intracellular calcium response and excitability of MSDB neurons.

    PubMed

    Wang, Jiangang; Wang, Yali; Wang, Yang; Wang, Ran; Zhang, Yunpeng; Zhang, Qian; Lu, Chengbiao

    2014-12-10

    The neurons of medial septal diagonal band of broca (MSDB) project to hippocampus and play an important role in MSDB-hippocampal synaptic transmission, plasticity and network oscillation. Nicotinic acetylcholine receptor (nAChR) subunits, α4β2 and α7 nAChRs, are expressed in MSDB neurons and permeable to calcium ions, which may modulate the function of MSDB neurons. The aims of this study are to determine the roles of selective nAChR activation on the calcium responses and membrane currents in MSDB neurons. Our results showed that nicotine increased calcium responses in the majority of MSDB neurons, pre-treatment of MSDB slices with a α4β2 nAChR antagonist, DhβE but not a α7 nAChR antagonist, MLA prevented nicotine-induced calcium responses. The whole cell patch clamp recordings showed that nicotine-induced inward current and acetylcholine (ACh) induced-firing activity can be largely reduced or prevented by DhβE in MSDB neurons. Surprisingly, post-treatment of α4β2 or α7 nAChR antagonists failed to block nicotine׳s role, they increased calcium responses instead. Application of calcium chelator EGTA reduced calcium responses in all neurons tested. These results suggest that there was a subtype specific modulation of nAChRs on calcium signaling and membrane currents in MSDB neurons and nAChR antagonists were also able to induce calcium responses involving a distinct mechanism.

  15. Neuroprotective effect of cellular prion protein (PrPC) is related with activation of alpha7 nicotinic acetylcholine receptor (α7nAchR)-mediated autophagy flux.

    PubMed

    Jeong, Jae-Kyo; Park, Sang-Youel

    2015-09-22

    Activation of the alpha7 nicotinic acetylcholine receptor (α7nAchR) is regulated by prion protein (PrPC) expression and has a neuroprotective effect by modulating autophagic flux. In this study, we hypothesized that PrPC may regulate α7nAchR activation and that may prevent prion-related neurodegenerative diseases by regulating autophagic flux. PrP(106-126) treatment decreased α7nAchR expression and activation of autophagic flux. In addition, the α7nAchR activator PNU-282987 enhanced autophagic flux and protected neuron cells against PrP(106-126)-induced apoptosis. However, activation of autophagy and the protective effects of PNU-282987 were inhibited in PrPC knockout hippocampal neuron cells. In addition, PrPC knockout hippocampal neuron cells showed decreased α7nAchR expression levels. Adenoviral overexpression of PrPC in PrPC knockout hippocampal neuron cells resulted in activation of autophagic flux and inhibition of prion peptide-mediated cell death via α7nAchR activation. This is the first report demonstrating that activation of α7nAchR-mediated autophagic flux is regulated by PrPC, and that activation of α7nAchR regulated by PrPC expression may play a pivotal role in protection of neuron cells against prion peptide-induced neuron cell death by autophagy. These results suggest that α7nAchR-mediated autophagic flux may be involved in the pathogenesis of prion-related diseases and may be a therapeutic target for prion-related neurodegenerative diseases.

  16. Neuroprotective effect of cellular prion protein (PrPC) is related with activation of alpha7 nicotinic acetylcholine receptor (α7nAchR)-mediated autophagy flux.

    PubMed

    Jeong, Jae-Kyo; Park, Sang-Youel

    2015-09-22

    Activation of the alpha7 nicotinic acetylcholine receptor (α7nAchR) is regulated by prion protein (PrPC) expression and has a neuroprotective effect by modulating autophagic flux. In this study, we hypothesized that PrPC may regulate α7nAchR activation and that may prevent prion-related neurodegenerative diseases by regulating autophagic flux. PrP(106-126) treatment decreased α7nAchR expression and activation of autophagic flux. In addition, the α7nAchR activator PNU-282987 enhanced autophagic flux and protected neuron cells against PrP(106-126)-induced apoptosis. However, activation of autophagy and the protective effects of PNU-282987 were inhibited in PrPC knockout hippocampal neuron cells. In addition, PrPC knockout hippocampal neuron cells showed decreased α7nAchR expression levels. Adenoviral overexpression of PrPC in PrPC knockout hippocampal neuron cells resulted in activation of autophagic flux and inhibition of prion peptide-mediated cell death via α7nAchR activation. This is the first report demonstrating that activation of α7nAchR-mediated autophagic flux is regulated by PrPC, and that activation of α7nAchR regulated by PrPC expression may play a pivotal role in protection of neuron cells against prion peptide-induced neuron cell death by autophagy. These results suggest that α7nAchR-mediated autophagic flux may be involved in the pathogenesis of prion-related diseases and may be a therapeutic target for prion-related neurodegenerative diseases. PMID:26295309

  17. Expression and function of striatal nAChRs differ in the flinders sensitive (FSL) and resistant (FRL) rat lines.

    PubMed

    Auta, J; Lecca, D; Nelson, M; Guidotti, A; Overstreet, D H; Costa, E; Javaid, J I

    2000-10-01

    Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by nicotine. In the present study, we measured dopamine (DA) content in striatal dialysates to investigate the sensitivity of FSL and FRL rats to nicotine delivered locally through a microdialysis probe placed in the striatum. We also measured the expression density of striatal high-affinity nicotinic acetylcholine receptors (nAChRs), and that of mRNAs encoding for alpha3, alpha4, alpha7 and beta2 nAChR subunits in both lines. The DA content of dialysates was measured before and after a 1-min perfusion of nicotine (6, 10 or 20 nmoles/min) and the resulting DA increase was taken as a measure of the alkaloid's intrinsic activity for nAChRs involved in the release of DA. The nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of nicotine, suggesting that the intrinsic activity of nicotine was greater in the FSL than in the FRL rats. This was further supported by our finding that the density of high-affinity nAChRs in the striatum of FSL rats was 44% greater than in the FRL rats, whereas affinity (K(D)) was virtually the same in the two lines of rats. Also the expression of mRNAs encoding for alpha(4), alpha(7), and beta(2) subunits in the striatum was greater in FSL than in FRL rats (attomol/microg total RNA, alpha(4):98+/-10 vs. 77+/-7; alpha(7):279+/-16 vs. 184+/-16; beta(2):310+/-19 vs. 201+/-12). We hypothesize that the difference in nicotine-induced DA release in the striatum of FSL and FRL rats depends on the difference in nAChR subunit expression in the striatum between the two lines. The Flinders rats could be used as a model for nicotine self-administration studies to evaluate the susceptibilities of FSL and FRL rats to nicotine dependence.

  18. Geological Mapping of the Ac-H-13 Urvara Quadrangle of Ceres from NASA's Dawn Mission

    NASA Astrophysics Data System (ADS)

    Sizemore, Hanna; Williams, David; Platz, Thomas; Mest, Scott; Yingst, Aileen; Crown, David; O'Brien, David; Buczkowski, Debra; Schenk, Paul; Scully, Jennifer; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Nathues, Andreas; De Sanctis, Maria Cristina; Russell, Christopher; Raymond, Carol

    2016-04-01

    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map, and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the geologic evolution of the Ac-H-13 Urvara Quadrangle. At the time of this writing LAMO images (35 m/pixel) are just becoming available. Thus, our geologic maps are based on HAMO images (140 m/pixel) and Survey (400 m/pixel) digital ter-rain models (for topographic information). Dawn Framing Camera (FC) color images are also used to provide context for map unit identification. The maps to be presented as posters will be updated from analyses of LAMO images. The Urvara Quadrangle is dominated by the 170-km diameter impact basin Urvara (46.4°S, 248.6°E) and includes cratered terrain to the west. Named features include the impact craters Meanderi (40.9°S, 193.7°E, 103 km diameter), Sekhet (66.4°S, 254.9°E, 41 km diameter), and Fluusa (31.5°S, 277.9°E), as well as the crater chains Gerber Catena (38.1°S, 214.8°E) and Sam-hain Catena (19.6°S, 210.3°E). Based on preliminary geologic mapping [3,4], we interpret the two prominent catenae as pit craters associated with large scale tectonism rather than secondary impacts. We interpret two large curvilinear depressions near the eastern quadrangle boundary as secondary crater chains resulting from the Urvara impact. Textural and morphological asymme-tries in crater materials within the quadrangle indicate heterogeneities in subsurface composition and volatile content. Features on the Urvara basin floor are consistent with impact fluidization of target materials; post impact extrusion of volatile rich material may have also played a minor role. References: [1] Williams D.A. et al. (2014) Icarus, 244, 1-12. [2] Yingst R.A. et al. (2014) PSS, 103, 2-23. [3] Sizemore et al. (2015) GSA Abstracts with Program

  19. Geological Mapping of the Ac-H-7 Kerwan Quadrangle of Ceres from NASA Dawn Mission.

    NASA Astrophysics Data System (ADS)

    Williams, David; Mest, Scott; Kneissl, Thomas; Hendrik Pasckert, Jan; Hiesinger, Harald; Neesemann, Adrian; Schmedemann, Nico; Buczkowski, Debra; Scully, Jennifer; Marchi, Simone; Schenk, Paul; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Nathues, Andreas; Schaefer, Michael; Hoffmann, Martin; Raymond, Carol; Russell, Christopher

    2016-04-01

    NASA's Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. Ac-H-7 Kerwan Quadrangle is located between 22°S-22°N and 72-144°E, and hosts several primary features and terrains: 1) The 280 km diameter impact basin Kerwan occur in the center and SE corner of the quad-rangle. Kerwan's rim is very degraded and there is no obvious ejecta field, indicating it is one of the oldest visible large impact basins on Ceres. Kerwan's interior is filled with a 'smooth terrain' that also extends beyond the rim to the east and west. This smooth terrain hosts a significantly lower impact crater density than most of the rest of Ceres' surface. Preliminary crater counts of the Kerwan smooth terrain derive cratering model ages of ~3 Ga using the lunar-derived chronology and ~600-800 Ma using the asteroid flux-derived chronology (H. Hiesinger, pers. comm., 2016). Our working interpretation is that the Kerwan impact occurred when Ceres' crust had a greater proportion of ice than at present, and that impact heating melted crustal material resulting in resurfacing of the Kerwan region by an icy impact melt, or possibly initiated cryovolcanic flows. There are hints of possible flow margins on the Kerwan floor in HAMO images, that have to be confirmed or denied by study of LAMO images. 2) Part of the 126 km diameter crater Dantu and its ejecta field covers the NE corner of the quadrangle. FC color data show both bright and dark materials in the ejecta field, suggesting ex-cavation of terrains of different compositions. Alternatively, because Dantu is one of two longitudes on Ceres where water vapor release has been detected [3], another interpretation is that the bright and/or dark deposits in the Dantu region could result from explosive cryovolcanism. Further study of LAMO data is required to investigate these hypotheses. 3) Other features include the

  20. Geological Mapping of the Ac-H-2 Coniraya Quadrangle of Ceres from NASA's Dawn Mission.

    NASA Astrophysics Data System (ADS)

    Hendrik Pasckert, Jan; Hiesinger, Harald; Williams, David; Crown, David; Mest, Scott; Buczkowski, Debra; Scully, Jennifer; Schmedemann, Nico; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Naß, Andrea; Nathues, Andreas; Hoffmann, Martin; Schäfer, Michael; De Sanctis, Maria Cristina; Raymond, Carol; Russell, Christopher

    2016-04-01

    Dwarf planet Ceres (˜950 km) is located at ˜2.8 AU in the main asteroid belt [1], and is currently orbited by NASA's Dawn spacecraft. Similar to Vesta [2], the 15 quadrangles of Ceres will be mapped on the basis of Framing Camera mosaics from Low Altitude Mapping Orbits (LAMO) with a spatial resolution of ˜35 m/px. Here we report on our preliminary geological map of the Ac-H-2 Coniraya Quadrangle (located between 21-66 ° N and 0-90 ° E) based on High Altitude Mapping Orbit (HAMO) data (˜120 m/px), as LAMO images are just becoming available. The Coniraya Quadrangle is dominated by craters of different sizes and degradation stages. Most of the craters are highly degraded and no ejecta blankets are visible (e.g., Coniraya: 136 km; 65.8° E/40.5° N). Only some craters like Gaue and Ikapati seem to be relatively fresh, and still have ejecta blankets. Such fresher impact craters could already be mapped in detail on HAMO data, and subdivided into crater ejecta, crater wall, crater floor, and crater central peak materials. At the crater floor and around Ikapati crater we also identified smooth materials that fill local depressions. The formation of the smooth material seems to be related to the formation of the impact crater, as crater densities of the smooth materials and the ejecta blanket are similar, as are their absolute model ages (AMAs), derived from crater size-frequency distribution (CSFD) measurements. Using the lunar derived chronology, CSFD measurements of Ikapati's ejecta blanket and the smooth materials located in and around the crater show AMAs of 300 to 390 Ma. CSFD measurements of Gaue crater show AMAs of 910-980 Ma. Both craters show background AMAs of 3.1 to 3.5 Ga, which might be related to old large craters (e.g., Coniraya or Kerwan). Apart from crater related units, we identified one dome-like structure (˜65 km wide; ˜3 km high) at the crater floor of a large degraded crater at the western edge of this quadrangle. This might be an indication

  1. Geological Mapping of the Ac-H-11 Sintana Quadrangle of Ceres from NASA's Dawn Mission.

    NASA Astrophysics Data System (ADS)

    Schulzeck, Franziska; Krohn, Katrin; Jaumann, Ralf; Williams, David A.; Buczkowski, Debra L.; Mest, Scott C.; Scully, Jennifer E. C.; Gathen, Isabel v. d.; Kersten, Elke; Matz, Klaus-Dieter; Naß, Andrea; Otto, Katharina; Pieters, Carle M.; Preusker, Frank; Roatsch, Thomas; De Sanctis, Maria C.; Schenk, Paul; Schröder, Stefanus; Stephan, Katrin; Wagner, Roland

    2016-04-01

    In December 2015, the Dawn spacecraft delivered the first images of the Low Altitude Mapping Orbit (LAMO) of the dwarf planet Ceres at a resolution of 35 m/pixel. This data will be used to finish the geological mapping of Ceres' surface in order to identify composition and surface forming processes. Mapping was already done using Survey Orbit and High Altitude Mapping Orbit (HAMO) data. With the new images, an updated map will be presented. To this point, the data material consists of a HAMO clear-filter mosaic (140 m/pixel) [1], a digital elevation model (DTM) [2] derived from Survey orbit (415 m/pixel) data, color-filter ratios and photometrically corrected images. Ceres' surface has been divided into 15 mapping quadrangles. The Ac-H-11 Sintana quadrangle is located in the southern hemisphere of Ceres between 21 66°S and 0 90°E. Geological units identified so far are cratered terrain, which covers most of the area, and a younger unit of relatively smooth material. The latter is characterized by a low crater density. Material of the same unit was found in adjacent quadrangles as well. Interest is taken in the diversity of crater shapes. Many craters show different forms of asymmetries. One and the same crater for instance displays different stages of rim degradation and some crater walls are partly terraced and their slopes' steepness is varying alongside the crater rim. Several mass wasting features, which partly cause the observed asymmetries, have been identified. Next to the multiple collapsed rims, landslides due to later cratering on the primary crater rim are observed. Whereas collapse structures are mostly blocky, single landslides are characterized by lobate margins. Occurrence and type of mass wasting feature might hint to subsurface differences. Further, there is a diversity of inner crater structures, like relaxed crater floors, ridges, central peaks, mounds and smooth plains. Processes like mass wasting and relaxation have modified many craters

  2. Cognitive Foundations for Visual Analytics

    SciTech Connect

    Greitzer, Frank L.; Noonan, Christine F.; Franklin, Lyndsey

    2011-02-25

    In this report, we provide an overview of scientific/technical literature on information visualization and VA. Topics discussed include an update and overview of the extensive literature search conducted for this study, the nature and purpose of the field, major research thrusts, and scientific foundations. We review methodologies for evaluating and measuring the impact of VA technologies as well as taxonomies that have been proposed for various purposes to support the VA community. A cognitive science perspective underlies each of these discussions.

  3. Assessment of the functionality and stability of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology.

    PubMed

    Padilla-Morales, Luis F; Colón-Sáez, José O; González-Nieves, Joel E; Quesada-González, Orestes; Lasalde-Dominicci, José A

    2016-01-01

    In our previous study we examined the functionality and stability of nicotinic acetylcholine receptor (nAChR)-detergent complexes (nAChR-DCs) from affinity-purified Torpedo californica (Tc) using fluorescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) and planar lipid bilayer (PLB) recordings for phospholipid and cholesterol like detergents. In the present study we enhanced the functional characterization of nAChR-DCs by recording macroscopic ion channel currents in Xenopus oocytes using the two electrode voltage clamp (TEVC). The use of TEVC allows for the recording of macroscopic currents elicited by agonist activation of nAChR-DCs that assemble in the oocyte plasma membrane. Furthermore, we examined the stability of nAChR-DCs, which is obligatory for the nAChR crystallization, using a 30 day FRAP assay in LCP for each detergent. The present results indicate a marked difference in the fractional fluorescence recovery (ΔFFR) within the same detergent family during the 30 day period assayed. Within the cholesterol analog family, sodium cholate and CHAPSO displayed a minimum ΔFFR and a mobile fraction (MF) over 80%. In contrast, CHAPS and BigCHAP showed a marked decay in both the mobile fraction and diffusion coefficient. nAChR-DCs containing phospholipid analog detergents with an alkylphosphocholine (FC) and lysofoscholine (LFC) of 16 carbon chains (FC-16, LFC-16) were more effective in maintaining a mobile fraction of over 80% compared to their counterparts with shorter acyl chain (C12, C14). The significant differences in macroscopic current amplitudes, activation and desensitization rates among the different nAChR-DCs evaluated in the present study allow to dissect which detergent preserves both, agonist activation and ion channel function. Functionality assays using TEVC demonstrated that LFC16, LFC14, and cholate were the most effective detergents in preserving macroscopic ion channel function, however, the nAChR-cholate complex

  4. Assessment of the functionality and stability of detergent purified nAChR from Torpedo using lipidic matrixes and macroscopic electrophysiology.

    PubMed

    Padilla-Morales, Luis F; Colón-Sáez, José O; González-Nieves, Joel E; Quesada-González, Orestes; Lasalde-Dominicci, José A

    2016-01-01

    In our previous study we examined the functionality and stability of nicotinic acetylcholine receptor (nAChR)-detergent complexes (nAChR-DCs) from affinity-purified Torpedo californica (Tc) using fluorescence recovery after photobleaching (FRAP) in Lipidic Cubic Phase (LCP) and planar lipid bilayer (PLB) recordings for phospholipid and cholesterol like detergents. In the present study we enhanced the functional characterization of nAChR-DCs by recording macroscopic ion channel currents in Xenopus oocytes using the two electrode voltage clamp (TEVC). The use of TEVC allows for the recording of macroscopic currents elicited by agonist activation of nAChR-DCs that assemble in the oocyte plasma membrane. Furthermore, we examined the stability of nAChR-DCs, which is obligatory for the nAChR crystallization, using a 30 day FRAP assay in LCP for each detergent. The present results indicate a marked difference in the fractional fluorescence recovery (ΔFFR) within the same detergent family during the 30 day period assayed. Within the cholesterol analog family, sodium cholate and CHAPSO displayed a minimum ΔFFR and a mobile fraction (MF) over 80%. In contrast, CHAPS and BigCHAP showed a marked decay in both the mobile fraction and diffusion coefficient. nAChR-DCs containing phospholipid analog detergents with an alkylphosphocholine (FC) and lysofoscholine (LFC) of 16 carbon chains (FC-16, LFC-16) were more effective in maintaining a mobile fraction of over 80% compared to their counterparts with shorter acyl chain (C12, C14). The significant differences in macroscopic current amplitudes, activation and desensitization rates among the different nAChR-DCs evaluated in the present study allow to dissect which detergent preserves both, agonist activation and ion channel function. Functionality assays using TEVC demonstrated that LFC16, LFC14, and cholate were the most effective detergents in preserving macroscopic ion channel function, however, the nAChR-cholate complex

  5. Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells

    PubMed Central

    Wu, Hongqiao; Zhang, Huilin; Zhang, Xiuping; Xiao, Dongjie; Ma, Xiaoli; Wang, Yunshan

    2016-01-01

    Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin. PMID:26909550

  6. A combined molecular docking and charge density analysis is a new approach for medicinal research to understand drug-receptor interaction: curcumin-AChE model.

    PubMed

    Renuga Parameswari, A; Rajalakshmi, G; Kumaradhas, P

    2015-01-01

    In the present study, a molecular docking analysis has been performed on diketone form of curcumin molecule with acetylcholinesterase (AChE). The calculated lowest docked energy of curcumin molecule in the active site of AChE is -11.21 kcal/mol; this high negative value indicates that the molecule exhibits large binding affinity towards AChE. When the curcumin molecule present in the active site of AChE, subsequently, its conformation has altered significantly and the molecule adopts a U-shape geometry as it is linear in gas phase (before entering into the active site). This conformational transition facilitates curcumin to form strong interaction with Phe330 of acyl-binding pocket and the choline binding site with indole ring of Trp84 and Asp72. The gas phase and the active site analysis of curcumin allows to understand the conformational geometry, nature of molecular flexibility, charge density redistribution and the variation of electrostatic properties of curcumin in the active site. To obtain the gas phase structure, the curcumin molecule was optimized using Hartree-Fock and density functional methods (B3LYP) with the basis set 6-311G(∗∗). A charge density analysis on both gas phase as well as the molecule lifted from the active site was carried out using Bader's theory of atoms in molecules (AIM). The difference in molecular electrostatic potential between the two forms of curcumin displays the difference in charge distribution. The large dipole moment of curcumin (7.54 D) in the active site reflects the charge redistribution as it is much less in the gas phase (4.34 D).

  7. Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

    PubMed

    Jia, Yanfei; Sun, Haiji; Wu, Hongqiao; Zhang, Huilin; Zhang, Xiuping; Xiao, Dongjie; Ma, Xiaoli; Wang, Yunshan

    2016-01-01

    Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin. PMID:26909550

  8. The linoleic acid derivative DCP-LA increases membrane surface localization of the α7 ACh receptor in a protein 4.1N-dependent manner.

    PubMed

    Kanno, Takeshi; Tsuchiya, Ayako; Tanaka, Akito; Nishizaki, Tomoyuki

    2013-03-01

    In yeast two-hybrid screening, protein 4.1N, a scaffolding protein, was identified as a binding partner of the α7 ACh (acetylcholine) receptor. For rat hippocampal slices, the linoleic acid derivative DCP-LA {8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid} increased the association of the α7 ACh receptor with 4.1N, and the effect was inhibited by GF109203X, an inhibitor of PKC (protein kinase C), although DCP-LA did not induce PKC phosphorylation of 4.1N. For PC-12 cells, the presence of the α7 ACh receptor in the plasma membrane fraction was significantly suppressed by knocking down 4.1N. DCP-LA increased the presence of the α7 ACh receptor in the plasma membrane fraction, and the effect was still inhibited by knocking down 4.1N. In the monitoring of α7 ACh receptor mobilization, DCP-LA enhanced signal intensities for the α7 ACh receptor at the membrane surface in PC-12 cells, which was clearly prevented by knocking down 4.1N. Taken together, the results of the present study show that 4.1N interacts with the α7 ACh receptor and participates in the receptor tethering to the plasma membrane. The results also indicate that DCP-LA increases membrane surface localization of the α7 ACh receptor in a 4.1N-dependent manner under the control of PKC, but without phosphorylating 4.1N.

  9. Nicotine Inhibits Cisplatin-Induced Apoptosis via Regulating α5-nAChR/AKT Signaling in Human Gastric Cancer Cells.

    PubMed

    Jia, Yanfei; Sun, Haiji; Wu, Hongqiao; Zhang, Huilin; Zhang, Xiuping; Xiao, Dongjie; Ma, Xiaoli; Wang, Yunshan

    2016-01-01

    Gastric cancer incidence demonstrates a strong etiologic association with smoking. Nicotine, the major component in tobacco, is a survival agonist that inhibits apoptosis induced by certain chemotherapeutic agents, but the precise mechanisms involved remain largely unknown. Recently studies have indicated that α5-nicotinic acetylcholine receptor (α5-nAChR) is highly associated with lung cancer risk and nicotine dependence. Nevertheless, no information has been available about whether nicotine also affects proliferation of human gastric cancer cells through regulation of α5-nAChR. To evaluate the hypothesis that α5-nAChR may play a role in gastric cancer, we investigated its expression in gastric cancer tissues and cell lines. The expression of α5-nAChR increased in gastric cancer tissue compared with para-carcinoma tissues. In view of the results, we proceeded to investigate whether nicotine inhibits cisplatin-induced apoptosis via regulating α5-nAChR in gastric cancer cell. The results showed that nicotine significantly promoted cell proliferation in a dose and time-dependent manner through α5-nAChR activation in human gastric cells. Furthermore, nicotine inhibited apoptosis induced by cisplatin. Silence of α5-nAChR ablated the protective effects of nicotine. However, when co-administrating LY294002, an inhibitor of PI3K/AKT pathway, an increased apoptosis was observed. This effect correlated with the induction of Bcl-2, Bax, Survivin and Caspase-3 by nicotine in gastric cell lines. These results suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutic drugs and that α5-nAChR/AKT signaling plays a key role in the anti-apoptotic activity of nicotine induced by cisplatin.

  10. Vertical Axis Wind Turbine Foundation parameter study

    SciTech Connect

    Lodde, P.F.

    1980-07-01

    The dynamic failure criterion governing the dimensions of prototype Vertical Axis Wind Turbine Foundations is treated as a variable parameter. The resulting change in foundation dimensions and costs is examined.

  11. Founding a Foundation: A Mini Case Study.

    ERIC Educational Resources Information Center

    Lake, Dale B.

    1981-01-01

    Lists factors contributing to the need for increased fund raising in community colleges. Discusses advantages of a foundation as a means of obtaining private funds. Delineates specifics of establishing, organizing, and implementing the Kalamazoo Valley Community College Foundation. (DMM)

  12. Chronic ethanol (EtOH) feeding increases muscarinic receptor (mAChR) density in esophagus without parallel change in dose response (D-R) to cholinergic agonists

    SciTech Connect

    Keshavarzian, A.; Gordon, J.H.; Urban, G.; Fields, J.Z. VA Hospital, Hines, IL )

    1991-03-11

    The mAChR/effector pathway for signal transduction is important in the physiology of esophagus and mAChR alterations are involved in EtOH induced changes in several organs. To see if EtOH-induced increases in lower esophageal sphincter pressure (LESP) are due to upregulation of mAChR, the authors evaluated mAChR binding and D-R curves for bethanechol (IV) induced increases in LESP, and compared these values to changes in LESP after acute and chronic EtOH. EtOH was given to cats acutely or chronically. The number of mAChR sites (Bmax) in esophagus was lowered by acute EtOH, withdrawal from chronic EtOH raised Bmax. Acute injection of EtOH to cats in withdrawal reversed this increase in mAChR density. These changes correlated with the earlier data on EtOH-induced changes in LESP. In contrast, the D-R curve for bethanechol shifted to the right. Thus, the withdrawal-associated increase in Bmax is more likely to be a compensatory response to deficits distal to the receptor recognition site than to proximal deficits and doesn't cause LESP hyperactivity. Also, receptor binding changes do not necessarily translate into physiological changes.

  13. Geological Mapping of the Ac-H-5 Fejokoo Quadrangle of Ceres from NASA's Dawn Mission

    NASA Astrophysics Data System (ADS)

    Hughson, Kynan; Russell, Christopher; Williams, David; Buczkowski, Debra; Mest, Scott; Scully, Jennifer; Kneissl, Thomas; Ruesch, Ottaviano; Frigeri, Alessandro; Combe, Jean-Philippe; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Platz, Thomas; Nathues, Andreas; Hoffmann, Martin; Schaefer, Michael; Park, Ryan; Marchi, Simone; Raymond, Carol

    2016-04-01

    NASA's Dawn spacecraft arrived at Ceres on March 6, 2015, and has been studying the dwarf planet through a series of successively lower orbits, obtaining morphological & topographical image, mineralogical, elemental abundance, and gravity data. Ceres is the largest object in the asteroid belt with a mean diameter of ~950 km. The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for the asteroid Vesta [1, 2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map, and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we present the LAMO-based geologic map of the Ac-H-5 Fejokoo quadrangle (21-66 °N and 270-360 °E) and discuss its geologic evolution. At the time of this writing LAMO images (35 m/pixel) are just becoming available. Thus, our geologic maps are based on HAMO images (~140 m/pixel) and Survey (~400 m/pixel) digital terrain models (for topographic information) [3, 4]. Dawn Framing Camera (FC) color images are also used to provide context for map unit identification. The maps to be presented as posters will be updated from analyses of LAMO images (~35 m/pixel). The Fejokoo quadrangle hosts six primary geologic features: (1) the centrally located, ~80 km diameter, distinctly hexagonal impact crater Fejokoo; (2) Victa crater with its large exterior dark lobate flow feature, and interior lobate and furrowed deposits; (3) Abellio crater, which exhibits a well formed ejecta blanket and has an arcuately textured infilled floor whose morphology is similar to those of homologously sized craters on some of the icy Saturnian satellites [5]; (4) Cozobi crater, whose floor is filled with an unusually bulbous and smooth deposit, thin sheeted multi-lobed flow-like features that are reminiscent of fluidized ejecta as seen on Mars are also observed to be emanating outwards from the N and S rims of this crater [6]; (5) the peculiar Oxo crater on the eastern

  14. Geological Mapping of the Ac-H-3 Dantu Quadrangle of Ceres from NASA's Dawn Mission.

    NASA Astrophysics Data System (ADS)

    Kneissl, Thomas; Schmedemann, Nico; Neesemann, Adrian; Williams, David A.; Crown, David A.; Mest, Scott C.; Buczkowski, Debra L.; Scully, Jennifer E. C.; Frigeri, Allessandro; Ruesch, Ottaviano; Hiesinger, Harald; Walter, Sebastian H. G.; Jaumann, Ralf; Roatsch, Thomas; Preusker, Frank; Kersten, Elke; Naß, Andrea; Nathues, Andreas; Platz, Thomas; Russell, Chistopher T.

    2016-04-01

    The Dawn Science Team is conducting a geologic mapping campaign for Ceres similar to that done for Vesta [1,2], including production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the geologic evolution of the Ac-H-3 Dantu Quadrangle. The current map is based on a Framing Camera (FC) clear-filter image mosaic from HAMO data (~140 m/px) as well as a digital terrain model (DTM) derived from imagery of the Survey phase [3]. Albedo variations were identified and mapped using a mosaic of photometrically corrected HAMO images provided by DLR. FC color images provided further context for map unit identification. LAMO images (35m/pixel), which have just become available at the time of writing, will be used to update the map to be presented as a poster. The quadrangle is located between 21-66°N and 90-180°E in a large-scale depression north of the impact basin Kerwan. The northern and southeastern parts of the quadrangle are characterized by cratered terrain while the south and southwest are dominated by the partially smooth ejecta blankets of craters Dantu and Gaue. East-west oriented pit/crater chains in the southern half of the quadrangle might be related to tectonic processes [4,5]. Dantu crater (d=~126 km) is a complex impact crater showing slump terraces and a partially smooth crater floor with concentric and radial fractures. Furthermore, Dantu shows a central pit structure with pitted terrain on its floor as well as several bright spots in the interior and exterior of the crater. High-resolution measurements of crater size-frequency distributions (CSFDs) superposed on Dantu indicate a formation/modification age of ~200 - 700 Ma. Most of the ejecta appear to be relatively bright and correspond to parts of the #2 high albedo region observed with the Hubble Space Telescope [6]. However, the southwestern portion of the ejecta blanket is

  15. Geological Mapping of the Ac-H-14 Yalode Quadrangle of Ceres from NASA's Dawn Mission

    NASA Astrophysics Data System (ADS)

    Crown, David; Yingst, Aileen; Mest, Scott; Platz, Thomas; Sizemore, Hanna; Berman, Daniel; Williams, David; Roatsch, Thomas; Preusker, Frank; Nathues, Andreas; Hoffman, Martin; Schäfer, Michael; Raymond, Carol; Russell, Christopher

    2016-04-01

    The Dawn Science Team is conducting a geologic mapping campaign for Ceres that includes production of a Survey- and High Altitude Mapping Orbit (HAMO)-based global map and a series of 15 Low Altitude Mapping Orbit (LAMO)-based quadrangle maps. In this abstract we discuss the surface geology and geologic evolution of the Ac-H-14 Yalode Quadrangle (21-66°S, 270-360°E). The current geologic map was produced using ArcGIS software based on HAMO images (140 m/pixel) for surface morphology and stratigraphic relationships, Survey (400 m/pixel) digital terrain models for topographic information, and Dawn Framing Camera (FC) color images as context for map unit identification. The map will be updated through analysis of LAMO images (35 m/pixel) that are just becoming available. The Yalode Quadrangle is dominated by the 260-km diameter impact basin Yalode (42.3°S, 293.6°E) and includes rugged and smooth terrains to the east. Preliminary geologic mapping defined two regional units (cratered terrain and smooth material), which dominate the quadrangle, as well as a series of impact crater material units. Mapped geologic features include crater rims, graben, ridges, troughs, scarp, lineaments, and impact crater chains. Geologic contacts are typically not distinct in Survey and HAMO images. Impact craters in Yalode Quadrangle display a range of preservation states. Degraded features, including Yalode basin and numerous smaller craters, exhibit subdued rims, lack discrete ejecta deposits, and have infilled interiors. More pristine features (including Mondamin, Besua, Lono and craters on the Yalode basin floor) have well-defined, quasi-circular forms with prominent rims and in some cases discernible ejecta. Some of these craters have bowl-shaped interiors, and others contain hills or mounds on their floors that are interpreted as central peaks. Yalode basin has a variably preserved rim, which is continuous and sharply defined to the north/northwest and is irregular or degraded

  16. Grantmaking to School Districts: Lessons for Foundations

    ERIC Educational Resources Information Center

    Coffman, Julia; Weiss, Heather; Harris, Erin; Little, Priscilla M. D.

    2010-01-01

    This brief offers lessons and best practices from foundations across the country on grantmaking to school districts. It offers advice to foundations that are considering school district investments for the first time. It also offers a useful "check" to more experienced foundations that want to examine their thinking and approaches against the…

  17. A Foundation Manual for California Community Colleges.

    ERIC Educational Resources Information Center

    Anderson, James M., Ed.; And Others

    Designed to aid the development and organization of effective college foundations in California, this reference guide reviews the purposes of foundations and the steps in their organization, providing sample documents from existing foundations. The manual is divided into 11 sections, the first of which discusses reasons for establishing…

  18. The Community College Foundation Manual & Guide.

    ERIC Educational Resources Information Center

    Anderson, James M., Comp.; Snyder, Tom, Comp.

    This collection of resources and information about community college foundations includes brief articles, selected data, materials from foundations, sample mission statements and articles of incorporation, sample forms and correspondence, relevant educational legislation, and other related materials from specific active foundations at two-year…

  19. Report on Illinois Public Community College Foundations.

    ERIC Educational Resources Information Center

    Illinois Community Coll. Board, Springfield.

    At the request of the Illinois Community College Board's (ICCB's) Committee on Foundations, the ICCB surveyed the state's public community college district to determine the purposes, resources, and activities of the colleges' foundations. The study found that all of the community college districts, except one, have foundations to assist them in…

  20. Bernard van Leer Foundation Annual Report 1996.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This document provides an annual report and financial review for 1996 of the Bernard van Leer Foundation, a private institution created in 1949 for broad humanitarian purposes. Following a summary by the executive director of the Foundation, the report includes a description of the foundation and its grants. It then lists, by country, the major…

  1. Bernard van Leer Foundation Annual Report, 1999.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This annual report details the activities and financial status for 1999 of the Bernard van Leer Foundation, a private institution created in 1949 for broad humanitarian purposes. Following the introduction by the chairman of the Foundation's board of trustees, the report of the executive director details activities during the Foundation's fiftieth…

  2. Bernard van Leer Foundation. Annual Report 1997.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This document provides an annual report and financial review of the Bernard van Leer Foundation, a private institution created in 1949 for broad humanitarian purposes. Following an introduction by the chairman of the Foundation's board of trustees, a report of the executive director details the first full-year of implementation of the Foundation's…

  3. Beyond Dependency: Strategies for Saving Foundations

    ERIC Educational Resources Information Center

    Schutz, Aaron; Butin, Dan

    2013-01-01

    The foundations field cannot sustain itself in its present condition. A range of complex forces have combined to marginalize foundations over the past few decades. The decline of this field as a separate discipline in schools of education has been abetted by the fact that foundations is generally a "service provider" to other programs.…

  4. Philanthropy and Private Foundations: Expanding Revenue Sources

    ERIC Educational Resources Information Center

    Drummer, Carlee; Marshburn, Roxann

    2014-01-01

    As community colleges seek new revenue streams, philanthropic organizations, including college foundations and private funders, have already begun to influence both revenues and college programming. This chapter discusses the current role of philanthropy, especially private foundations such as the Lumina Foundation for Education and the Bill and…

  5. {alpha}7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis.

    PubMed

    Abdrakhmanova, Galya R; AlSharari, Shakir; Kang, Minho; Damaj, M Imad; Akbarali, Hamid I

    2010-09-01

    Controlled clinical trials of nicotine transdermal patch for treatment of ulcerative colitis have been shown to improve histological and global clinical scores of colitis. Here we report that nicotine (1 microM) suppresses in vitro hyperexcitability of colonic dorsal root ganglia (DRG) (L(1)-L(2)) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation. Nicotine gradually reduced regenerative multiple-spike action potentials in colitis mice to a single action potential. Nicotine's effect on hyperexcitability of inflamed neurons was blocked in the presence of an alpha(7)-nicotinic acetylcholine receptor (nAChR) antagonist, methyllicaconitine, while choline, the alpha(7)-nAChR agonist, induced a similar effect to that of nicotine. Consistent with these findings, nicotine failed to suppress hyperexcitability in colonic DRG neurons from DSS-treated alpha(7) knockout mice. Furthermore, colonic DRG neurons from DSS-treated alpha(7) knockout mice were characterized by lower rheobase (10 +/- 5 vs. 77 +/- 13 pA, respectively) and current threshold (28 +/- 4 vs. 103 +/- 8 pA, respectively) levels than DSS-treated C57BL/J6 mice. An interesting observation of this study is that 8 of 12 colonic DRG (L(1)-L(2)) neurons from control alpha(7) knockout mice exhibited multiple-spike action potential firing while no wild-type neurons did. Overall, our findings suggest that nicotine at low 1 microM concentration suppresses in vitro hyperexcitability of inflamed colonic DRG neurons in a mouse model of acute colonic inflammation via activation of alpha(7)-nAChRs.

  6. Nicotinic acetylcholine receptors (nAChRs) at zebrafish red and white muscle show different properties during development.

    PubMed

    Ahmed, Kazi T; Ali, Declan W

    2016-08-01

    Nicotinic acetylcholine receptors (nAChRs) are highly expressed at the vertebrate neuromuscular junction (NMJ) where they are required for muscle activation. Understanding the factors that underlie NMJ development is critical for a full understanding of muscle function. In this study we performed whole cell and outside-out patch clamp recordings, and single-cell RT-qPCR from zebrafish red and white muscle to examine the properties of nAChRs during the first 5 days of development. In red fibers miniature endplate currents (mEPCs) exhibit single exponential time courses at 1.5 days postfertilization (dpf) and double exponential time courses from 2 dpf onwards. In white fibers, mEPCs decay relatively slowly, with a single exponential component at 1.5 dpf. By 2 and 3 dpf, mEPC kinetics speed up, and decay with a double exponential component, and by 4 dpf the exponential decay reverts back to a single component. Single channel recordings confirm the presence of two main conductance classes of nAChRs (∼45 pS and ∼65 pS) in red fibers with multiple time courses. Two main conductance classes are also present in white fibers (∼55 pS and ∼73 pS), but they exhibit shorter mean open times by 5 dpf compared with red muscle. RT-qPCR of mRNA for nicotinic receptor subunits supports a switch from γ to ε subunits in white fibers but not in red. Our findings provide a developmental profile of mEPC properties from red and white fibers in embryonic and larval zebrafish, and reveal previously unknown differences between the NMJs of these muscle fibers.© 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 916-936, 2016.

  7. Topographic Characterization of Cu-Ni NPs @ a-C:H Films by AFM and Multifractal Analysis.

    PubMed

    Ţălu, Ştefan; Stach, Sebastian; Ghodselahi, Tayebeh; Ghaderi, Atefeh; Solaymani, Shahram; Boochani, Arash; Garczyk, Żaneta

    2015-04-30

    In the present work three-dimensional (3-D) surface topography of Cu-Ni nanoparticles in hydrogenated amorphous carbon (Cu-Ni NPs @ a-C:H) with constant thickness of Cu and three thicknesses of Ni prepared by RF-Plasma Enhanced Chemical Vapor Deposition (RF-PECVD) system were investigated. The thin films of Cu-Ni NPs @ a-C:H with constant thickness of Cu and three thicknesses of Ni deposited by radio frequency (RF)-sputtering and RF-PECVD systems, were characterized. To determine the mass thickness and atomic structure of the films, the Rutherford backscattering spectroscopy (RBS) spectra was applied. The absorption spectra were applied to study localized surface plasmon resonance (LSPR) peaks of Cu-Ni NPs (observed around 608 nm in visible spectra), which is widened and shifted to lower wavelengths as the thickness of Ni over layer increases, and their changes are also evaluated by the 3-D surface topography. These nanostructures were investigated over square areas of 1 μm × 1 μm using atomic force microscopy (AFM) and multifractal analysis. Topographic characterization of surface samples (in amplitude, spatial distribution, and pattern of surface characteristics) highlighted 3-D surfaces with multifractal features which can be quantitatively estimated by the multifractal measures. The 3-D surface topography Cu-Ni NPs @ a-C:H with constant thickness of Cu and three thicknesses of Ni prepared by RF-PECVD system can be characterized using the multifractal geometry in correlation with the surface statistical parameters. PMID:25839675

  8. Nicotine activates YAP1 through nAChRs mediated signaling in esophageal squamous cell cancer (ESCC).

    PubMed

    Zhao, Yue; Zhou, Wei; Xue, Liyan; Zhang, Weimin; Zhan, Qimin

    2014-01-01

    Cigarette smoking is an established risk factor for esophageal cancers. Yes-associated protein 1 (YAP1), the key transcription factor of the mammalian Hippo pathway, has been reported to be an oncogenic factor for many cancers. In this study, we find nicotine administration can induce nuclear translocation and activation of YAP1 in ESCC. Consistently, we observed nuclear translocation and activation of YAP1 by knockdown of CHRNA3, which is a negative regulator of nicotine signaling in bronchial and esophageal cancer cells. Nicotine administration or CHRNA3 depletion substantially increased proliferation and migration in esophageal cancer cells. Interestingly, we find that YAP1 physically interacts with nAChRs, and nAChRs-signaling dissociates YAP1 from its negative regulatory complex composed with α-catenin, β-catenin and 14-3-3 in the cytoplasm, leading to upregulation and nuclear translocation of YAP1. This process likely requires PKC activation, as PKC specific inhibitor Enzastaurin can block nicotine induced YAP1 activation. In addition, we find nicotine signaling also inhibits the interaction of YAP1 with P63, which contributes to the inhibitory effect of nicotine on apoptosis. Using immunohistochemistry analysis we observed upregulation of YAP1 in a significant portion of esophageal cancer samples. Consistently, we have found a significant association between YAP1 upregulation and cigarette smoking in the clinical esophageal cancer samples. Together, these findings suggest that the nicotine activated nAChRs signaling pathway which further activates YAP1 plays an important role in the development of esophageal cancer, and this mechanism may be of a general significance for the carcinogenesis of smoking related cancers.

  9. The identification and restitution of human remains from an Aché girl named "Damiana": an interdisciplinary approach.

    PubMed

    Koel-Abt, Katrin; Winkelmann, Andreas

    2013-10-01

    In June 2010, the postcranial skeleton of an adolescent girl was returned by the Natural History Museum of La Plata, Argentina, to the Aché community in Paraguay. In March 2011 the missing skull was identified in the anatomical collection of Charité in Berlin. We initiated a historical and anthropological investigation to confirm the identity of the human remains and to reconstruct the fate of the individual in question in its historical context. Anthropological publications from Argentina had indicated that the girl named "Damiana" was abducted by colonising settlers in Southern Paraguay in 1897 at the age of 3-4 years, later taken to La Plata in Argentina where she grew up as a "maidservant", and died in 1907 of "galloping consumption". In accordance with these reports, the present palaeopathological investigation confirms tuberculous meningitis as a likely cause of death. It also demonstrates some markers of "stress", the nature of which, however, is difficult to determine. Surviving letters and publications by Berlin anatomist Hans Virchow reveal that the girl's preserved head was sent from La Plata to Berlin in January 1908 for comparative investigations in the context of the racial theories of the time. We were convinced that the justified wishes of the Aché community to bury these remains alongside those restituted in 2010 outweighed any future scientific interest in these remains. In April 2012, the skull and two related specimens were returned from the Charité to the Aché community, mediated by the Paraguayan ambassador in Berlin.

  10. Topographic Characterization of Cu-Ni NPs @ a-C:H Films by AFM and Multifractal Analysis.

    PubMed

    Ţălu, Ştefan; Stach, Sebastian; Ghodselahi, Tayebeh; Ghaderi, Atefeh; Solaymani, Shahram; Boochani, Arash; Garczyk, Żaneta

    2015-04-30

    In the present work three-dimensional (3-D) surface topography of Cu-Ni nanoparticles in hydrogenated amorphous carbon (Cu-Ni NPs @ a-C:H) with constant thickness of Cu and three thicknesses of Ni prepared by RF-Plasma Enhanced Chemical Vapor Deposition (RF-PECVD) system were investigated. The thin films of Cu-Ni NPs @ a-C:H with constant thickness of Cu and three thicknesses of Ni deposited by radio frequency (RF)-sputtering and RF-PECVD systems, were characterized. To determine the mass thickness and atomic structure of the films, the Rutherford backscattering spectroscopy (RBS) spectra was applied. The absorption spectra were applied to study localized surface plasmon resonance (LSPR) peaks of Cu-Ni NPs (observed around 608 nm in visible spectra), which is widened and shifted to lower wavelengths as the thickness of Ni over layer increases, and their changes are also evaluated by the 3-D surface topography. These nanostructures were investigated over square areas of 1 μm × 1 μm using atomic force microscopy (AFM) and multifractal analysis. Topographic characterization of surface samples (in amplitude, spatial distribution, and pattern of surface characteristics) highlighted 3-D surfaces with multifractal features which can be quantitatively estimated by the multifractal measures. The 3-D surface topography Cu-Ni NPs @ a-C:H with constant thickness of Cu and three thicknesses of Ni prepared by RF-PECVD system can be characterized using the multifractal geometry in correlation with the surface statistical parameters.

  11. Deontological foundations for medical ethics?

    PubMed

    Gillon, R

    1985-05-01

    Gillon outlines the principles of the deontological, or duty-based, group of moral theories in one of a series of British Medical Journal articles on the philosophical foundations of medical ethics. He differentiates between monistic theories, such as Immanuel Kant's, which rely on a single moral principle, and pluralistic theories, such as that of W.D. Ross, which rely on several principles that potentially could conflict. He summarizes the contributions of Kant and Ross to the development of deontological thought, then concludes his essay with brief paragraphs on other deontological approaches to the resolution of conflicting moral principles.

  12. EVOLUTIONARY FOUNDATIONS FOR MOLECULAR MEDICINE

    PubMed Central

    Nesse, Randolph M.; Ganten, Detlev; Gregory, T. Ryan; Omenn, Gilbert S.

    2015-01-01

    Evolution has long provided a foundation for population genetics, but many major advances in evolutionary biology from the 20th century are only now being applied in molecular medicine. They include the distinction between proximate and evolutionary explanations, kin selection, evolutionary models for cooperation, and new strategies for tracing phylogenies and identifying signals of selection. Recent advances in genomics are further transforming evolutionary biology and creating yet more opportunities for progress at the interface of evolution with genetics, medicine, and public health. This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and others to speed the development of evolutionary molecular medicine. PMID:22544168

  13. The shifting foundations of nursing.

    PubMed

    Law, Kate; Aranda, Kay

    2010-08-01

    In this paper we argue that the concerns generated by the development of Foundation Degrees and the Assistant and Associate Practitioner roles have rekindled some of the unresolved debates regarding the status and identity of nursing and nurses. Through the application of the sociological theories of professionalisation and nostalgia we have identified the shifting and unresolved nature of nursing. We argue that these theories continue to have resonance in the current climate of change and 'upskilling' of the health care workforce and argue, that the shifts illuminated are perhaps so significant as to demonstrate that we have entered a post-nursing era.

  14. Improved resolution of single channel dwell times reveals mechanisms of binding, priming, and gating in muscle AChR.

    PubMed

    Mukhtasimova, Nuriya; daCosta, Corrie J B; Sine, Steven M

    2016-07-01

    The acetylcholine receptor (AChR) from vertebrate skeletal muscle initiates voluntary movement, and its kinetics of activation are crucial for maintaining the safety margin for neuromuscular transmission. Furthermore, the kinetic mechanism of the muscle AChR serves as an archetype for understanding activation mechanisms of related receptors from the Cys-loop superfamily. Here we record currents through single muscle AChR channels with improved temporal resolution approaching half an order of magnitude over our previous best. A range of concentrations of full and partial agonists are used to elicit currents from human wild-type and gain-of-function mutant AChRs. For each agonist-receptor combination, rate constants are estimated from maximum likelihood analysis using a kinetic scheme comprised of agonist binding, priming, and channel gating steps. The kinetic scheme and rate constants are tested by stochastic simulation, followed by incorporation of the experimental step response, sampling rate, background noise, and filter bandwidth. Analyses of the simulated data confirm all rate constants except those for channel gating, which are overestimated because of the established effect of noise on the briefest dwell times. Estimates of the gating rate constants were obtained through iterative simulation followed by kinetic fitting. The results reveal that the agonist association rate constants are independent of agonist occupancy but depend on receptor state, whereas those for agonist dissociation depend on occupancy but not on state. The priming rate and equilibrium constants increase with successive agonist occupancy, and for a full agonist, the forward rate constant increases more than the equilibrium constant; for a partial agonist, the forward rate and equilibrium constants increase equally. The gating rate and equilibrium constants also increase with successive agonist occupancy, but unlike priming, the equilibrium constants increase more than the forward rate

  15. A geometricla error in some Computer Programs based on the Aki-Christofferson-Husebye (ACH) Method of Teleseismic Tomography

    USGS Publications Warehouse

    Julian, B.R.; Evans, J.R.; Pritchard, M.J.; Foulger, G.R.

    2000-01-01

    Some computer programs based on the Aki-Christofferson-Husebye (ACH) method of teleseismic tomography contain an error caused by identifying local grid directions with azimuths on the spherical Earth. This error, which is most severe in high latitudes, introduces systematic errors into computed ray paths and distorts inferred Earth models. It is best dealt with by explicity correcting for the difference between true and grid directions. Methods for computing these directions are presented in this article and are likely to be useful in many other kinds of regional geophysical studies that use Cartesian coordinates and flat-earth approximations.

  16. Acute toxicity of a commercial glyphosate formulation on European sea bass juveniles (Dicentrarchus labrax L.): gene expressions of heme oxygenase-1 (ho-1), acetylcholinesterase (AChE) and aromatases (cyp19a and cyp19b).

    PubMed

    Prevot-D'Alvise, N; Richard, S; Coupé, S; Bunet, R; Grillasca, J P

    2013-12-31

    Acute toxicity of Roundup, a commercial glyphosate--based herbicide, was evaluated in a teleost marine fish, the European sea bass, after 96 h of exposure. The LC50 96-h value of Roundup was 529 mg/L. Juveniles (Dicentrarchus labrax L.) were exposed to a sublethal concentration (35% of the LC50, i.e. 193 mg/L) of Roundup for 96-h. The study of heme oxygenase-1 (ho-1) gene expression was performed in four tissues (liver, gills, brain and gonads) and highlighted the disruption of antioxidant defence system. Results showed that ho-1 mRNA levels in liver and gills significantly decreased (p<0.001 and p<0.01 respectively) in fish exposed to 193 mg/L of Roundup, whereas in brain and gonads, ho-1 mRNA level was not altered. The analysis of acetylcholinesterase expression was used to evaluate the overall neurotoxicity of the herbicide and aromatase genes to assess the alteration of the endocrine system. Results showed that AChE and cyp19b gene transcriptions significantly increased (p<0.01) in brain of sea bass, whereas aromatase gene expression (cyp19a) in gonads was not significantly altered. Our results showed complex tissue-specific transcriptional responses after 96 h of exposure to a sublethal concentration. All these disruptions confirmed the deleterious effects of this glyphosate-based herbicide in a marine species.

  17. α4β2 nicotinic receptors play a role in the nAChR-mediated decline in L-dopa-induced dyskinesias in parkinsonian rats

    PubMed Central

    Quik, Maryka; Campos, Carla; Bordia, Tanuja; Strachan, Jon-Paul; Zhang, Jenny; McIntosh, J. Michael; Letchworth, Sharon; Jordan, Kristen

    2013-01-01

    L-dopa-induced dyskinesias are a serious long-term side effect of dopamine replacement therapy for Parkinson’s disease for which there are few treatment options. Our previous studies showed that nicotine decreased L-dopa-induced abnormal involuntary movements (AIMs). Subsequent work with knockout mice demonstrated that α6β2* nicotinic receptors (nAChRs) play a key role. The present experiments were done to determine if α4β2* nAChRs are also involved in L-dopa-induced dyskinesias. To approach this, we took advantage of the finding that α6β2* nAChRs are predominantly present on striatal dopaminergic nerve terminals, while a significant population of α4β2* nAChRs are located on other neurons. Thus, a severe dopaminergic lesion would cause a major loss in α6β2*, but not α4β2* nAChRs. Experiments were therefore done in which rats were unilaterally lesioned with 6-hydroxydopamine, at a dose that lead to severe nigrostriatal damage. The dopamine transporter, a dopamine nerve terminal marker, was decreased by >99%. This lesion also decreased striatal α6β2* nAChRs by 97%, while α4β2* nAChRs were reduced by only 12% compared to control. A series of β2* nAChR compounds, including TC-2696, TI-10165, TC-8831, TC-10600 and sazetidine reduced L-dopa-induced AIMs in these rats by 23–32%. TC-2696, TI-10165, TC-8831 were also tested for parkinsonism, with no effect on this behavior. Tolerance did not develop with up to 3 months of treatment. Since α4a5β2 nAChRs are also predominantly on striatal dopamine terminals, these data suggest that drugs targeting α4β2 nAChRs may reduce L-dopa-induced dyskinesias in late stage Parkinson’s disease. PMID:23583932

  18. Foundations for offshore wind turbines.

    PubMed

    Byrne, B W; Houlsby, G T

    2003-12-15

    An important engineering challenge of today, and a vital one for the future, is to develop and harvest alternative sources of energy. This is a firm priority in the UK, with the government setting a target of 10% of electricity from renewable sources by 2010. A component central to this commitment will be to harvest electrical power from the vast energy reserves offshore, through wind turbines or current or wave power generators. The most mature of these technologies is that of wind, as much technology transfer can be gained from onshore experience. Onshore wind farms, although supplying 'green energy', tend to provoke some objections on aesthetic grounds. These objections can be countered by locating the turbines offshore, where it will also be possible to install larger capacity turbines, thus maximizing the potential of each wind farm location. This paper explores some civil-engineering problems encountered for offshore wind turbines. A critical component is the connection of the structure to the ground, and in particular how the load applied to the structure is transferred safely to the surrounding soil. We review previous work on the design of offshore foundations, and then present some simple design calculations for sizing foundations and structures appropriate to the wind-turbine problem. We examine the deficiencies in the current design approaches, and the research currently under way to overcome these deficiencies. Designs must be improved so that these alternative energy sources can compete economically with traditional energy suppliers. PMID:14667305

  19. Foundations for offshore wind turbines.

    PubMed

    Byrne, B W; Houlsby, G T

    2003-12-15

    An important engineering challenge of today, and a vital one for the future, is to develop and harvest alternative sources of energy. This is a firm priority in the UK, with the government setting a target of 10% of electricity from renewable sources by 2010. A component central to this commitment will be to harvest electrical power from the vast energy reserves offshore, through wind turbines or current or wave power generators. The most mature of these technologies is that of wind, as much technology transfer can be gained from onshore experience. Onshore wind farms, although supplying 'green energy', tend to provoke some objections on aesthetic grounds. These objections can be countered by locating the turbines offshore, where it will also be possible to install larger capacity turbines, thus maximizing the potential of each wind farm location. This paper explores some civil-engineering problems encountered for offshore wind turbines. A critical component is the connection of the structure to the ground, and in particular how the load applied to the structure is transferred safely to the surrounding soil. We review previous work on the design of offshore foundations, and then present some simple design calculations for sizing foundations and structures appropriate to the wind-turbine problem. We examine the deficiencies in the current design approaches, and the research currently under way to overcome these deficiencies. Designs must be improved so that these alternative energy sources can compete economically with traditional energy suppliers.

  20. Biochemical and functional properties of distinct nicotinic acetylcholine receptors in the superior cervical ganglion of mice with targeted deletions of nAChR subunit genes.

    PubMed

    David, Reinhard; Ciuraszkiewicz, Anna; Simeone, Xenia; Orr-Urtreger, Avi; Papke, Roger L; McIntosh, J M; Huck, Sigismund; Scholze, Petra

    2010-03-01

    Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in ganglia of the autonomic nervous system. Here, we determined the subunit composition of hetero-pentameric nAChRs in the mouse superior cervical ganglion (SCG), the function of distinct receptors (obtained by deletions of nAChR subunit genes) and mechanisms at the level of nAChRs that might compensate for the loss of subunits. As shown by immunoprecipitation and Western blots, wild-type (WT) mice expressed: alpha 3 beta 4 (55%), alpha 3 beta 4 alpha 5 (24%) and alpha 3 beta 4 beta 2 (21%) nAChRs. nAChRs in beta 4 knockout (KO) mice were reduced to < 15% of controls and no longer contained the alpha 5 subunit. Compound action potentials, recorded from the postganglionic (internal carotid) nerve and induced by preganglionic nerve stimulation, did not differ between alpha 5 beta 4 KO and WT mice, suggesting that the reduced number of receptors in the KO mice did not impair transganglionic transmission. Deletions of alpha 5 or beta2 did not affect the overall number of receptors and we found no evidence that the two subunits substitute for each other. In addition, dual KOs allowed us to study the functional properties of distinct alpha 3 beta4 and alpha 3 beta 2 receptors that have previously only been investigated in heterologous expression systems. The two receptors strikingly differed in the decay of macroscopic currents, the efficacy of cytisine, and their responses to the alpha-conotoxins AuIB and MII. Our data, based on biochemical and functional experiments and several mouse KO models, clarify and significantly extend previous observations on the function of nAChRs in heterologous systems and the SCG. PMID:20377613

  1. Pyridostigmine but not 3,4-diaminopyridine exacerbates ACh receptor loss and myasthenia induced in mice by muscle-specific kinase autoantibody

    PubMed Central

    Morsch, Marco; Reddel, Stephen W; Ghazanfari, Nazanin; Toyka, Klaus V; Phillips, William D

    2013-01-01

    In myasthenia gravis, the neuromuscular junction is impaired by the antibody-mediated loss of postsynaptic acetylcholine receptors (AChRs). Muscle weakness can be improved upon treatment with pyridostigmine, a cholinesterase inhibitor, or with 3,4-diaminopyridine, which increases the release of ACh quanta. The clinical efficacy of pyridostigmine is in doubt for certain forms of myasthenia. Here we formally examined the effects of these compounds in the antibody-induced mouse model of anti-muscle-specific kinase (MuSK) myasthenia gravis. Mice received 14 daily injections of IgG from patients with anti-MuSK myasthenia gravis. This caused reductions in postsynaptic AChR densities and in endplate potential amplitudes. Systemic delivery of pyridostigmine at therapeutically relevant levels from days 7 to 14 exacerbated the anti-MuSK-induced structural alterations and functional impairment at motor endplates in the diaphragm muscle. No such effect of pyridostigmine was found in mice receiving control human IgG. Mice receiving smaller amounts of MuSK autoantibodies did not display overt weakness, but 9 days of pyridostigmine treatment precipitated generalised muscle weakness. In contrast, one week of treatment with 3,4-diaminopyridine enhanced neuromuscular transmission in the diaphragm muscle. Both pyridostigmine and 3,4-diaminopyridine increase ACh in the synaptic cleft yet only pyridostigmine potentiated the anti-MuSK-induced decline in endplate ACh receptor density. These results thus suggest that ongoing pyridostigmine treatment potentiates anti-MuSK-induced AChR loss by prolonging the activity of ACh in the synaptic cleft. PMID:23440963

  2. Partnering: The foundation for performance

    SciTech Connect

    Edelman, L.

    1994-12-31

    Over the past several decades, the US has experienced an unprecedented increase in the number of disputes in litigation. The environmental area, particularly contracts involving remediation projects, have not been immune from this situation. The adverse impact of this litigation mindset on the financial and personnel resources of the contracting parties has escalated and the detrimental effect on contractual relationships has become more apparent. Both owners and contractors are confronted with unrealized contract expectations, hostility on the jobsite and disappointment in the traditional dispute resolution processes. Relying exclusively on litigation when negotiations fail to settle contract disputes is time consuming, costly and frustrating. Now in the 1990s, the Corps along with the construction industry are moving to establish a new relationship beneficial to all contracting parties that focus on disputes avoidance. This new relationship is fostered by a process called Partnering. In undertaking environmental remediation work, Partnering can lay the foundation for a successful relationship among all involved parties.

  3. The foundation of kinship: Households

    PubMed Central

    Leonetti, Donna L.; Chabot-Hanowell, Benjamin

    2011-01-01

    Men’s hunting has dominated the discourse on energy capture and flow in the past decade or so. We turn to women’s roles as critical to household formation, pair bonding and intergenerational bonds. Their pivotal contributions in food processing and distribution likely promoted kinship, both genetic and affinal, and appear to be the foundation from which households evolved. With conscious recognition of household social units, variable cultural constructions of human kinship systems could emerge that were sensitive to environmental and technological conditions. Kinship dramatically altered the organization of resource access for our species creating what we term “kinship ecologies.” We present simple mathematical models to show how hunting leads to dependence on women’s contributions, bonds men to women and generations together. Kinship, as it organized transfers of food and labor energy centered on women, also became integrated with the biological evolution of human reproduction and life history. PMID:21799658

  4. Foundation Depth for Bridge Piers

    NASA Astrophysics Data System (ADS)

    Veerappadevaru, G.; Gangadharaiah, T.; Jagadeesh, T. R.

    2013-09-01

    The safety of bridge piers built in rivers having the bed is one of the prime aspects in the study of scouring process around bridge piers. The stability of bridge piers depends on the depth of foundation provided below maximum scour level. The stability analysis of bridge piers is carried based on moment of forces acting on the caisson pier when the pier slides and tilts slightly in downstream from its position. The experiments are conducted for three pier shapes on two sediment beds and for different flow conditions. The curves indicating the stability limits are compared with Lacey's recommendations which are used in present day practice in India. The analysis presented here indicates that the Lacey's recommendation for railway bridges is safe and for some cases of the road bridges depends on grip length, angle of tilt and weight of caisson.

  5. Emotional foundations of cognitive control.

    PubMed

    Inzlicht, Michael; Bartholow, Bruce D; Hirsh, Jacob B

    2015-03-01

    Often seen as the paragon of higher cognition, here we suggest that cognitive control is dependent on emotion. Rather than asking whether control is influenced by emotion, we ask whether control itself can be understood as an emotional process. Reviewing converging evidence from cybernetics, animal research, cognitive neuroscience, and social and personality psychology, we suggest that cognitive control is initiated when goal conflicts evoke phasic changes to emotional primitives that both focus attention on the presence of goal conflicts and energize conflict resolution to support goal-directed behavior. Critically, we propose that emotion is not an inert byproduct of conflict but is instrumental in recruiting control. Appreciating the emotional foundations of control leads to testable predictions that can spur future research.

  6. Emotional foundations of cognitive control

    PubMed Central

    Inzlicht, Michael; Bartholow, Bruce D.; Hirsh, Jacob B.

    2015-01-01

    Often seen as the paragon of higher cognition, here we suggest that cognitive control is dependent on emotion. Rather than asking whether control is influenced by emotion, we ask whether control itself can be understood as an emotional process. Reviewing converging evidence from cybernetics, animal research, cognitive neuroscience, and social and personality psychology, we suggest that cognitive control is initiated when goal conflicts evoke phasic changes to emotional primitives that both focus attention on the presence of goal conflicts and energize conflict resolution to support goal-directed behavior. Critically, we propose that emotion is not an inert byproduct of conflict but is instrumental in recruiting control. Appreciating the emotional foundations of control leads to testable predictions that can spur future research. PMID:25659515

  7. PACAP induces plasticity at autonomic synapses by nAChR-dependent NOS1 activation and AKAP-mediated PKA targeting.

    PubMed

    Jayakar, Selwyn S; Pugh, Phyllis C; Dale, Zack; Starr, Eric R; Cole, Samantha; Margiotta, Joseph F

    2014-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide found at synapses throughout the central and autonomic nervous system. We previously found that PACAP engages a selective G-protein coupled receptor (PAC1R) on ciliary ganglion neurons to rapidly enhance quantal acetylcholine (ACh) release from presynaptic terminals via neuronal nitric oxide synthase (NOS1) and cyclic AMP/protein kinase A (PKA) dependent processes. Here, we examined how PACAP stimulates NO production and targets resultant outcomes to synapses. Scavenging extracellular NO blocked PACAP-induced plasticity supporting a retrograde (post- to presynaptic) NO action on ACh release. Live-cell imaging revealed that PACAP stimulates NO production by mechanisms requiring NOS1, PKA and Ca(2+) influx. Ca(2+)-permeable nicotinic ACh receptors composed of α7 subunits (α7-nAChRs) are potentiated by PKA-dependent PACAP/PAC1R signaling and were required for PACAP-induced NO production and synaptic plasticity since both outcomes were drastically reduced following their selective inhibition. Co-precipitation experiments showed that NOS1 associates with α7-nAChRs, many of which are perisynaptic, as well as with heteromeric α3*-nAChRs that generate the bulk of synaptic activity. NOS1-nAChR physical association could facilitate NO production at perisynaptic and adjacent postsynaptic sites to enhance focal ACh release from juxtaposed presynaptic terminals. The synaptic outcomes of PACAP/PAC1R signaling are localized by PKA anchoring proteins (AKAPs). PKA regulatory-subunit overlay assays identified five AKAPs in ganglion lysates, including a prominent neuronal subtype. Moreover, PACAP-induced synaptic plasticity was selectively blocked when PKA regulatory-subunit binding to AKAPs was inhibited. Taken together, our findings indicate that PACAP/PAC1R signaling coordinates nAChR, NOS1 and AKAP activities to induce targeted, retrograde plasticity at autonomic synapses. Such

  8. 3D MI-DRAGON: new model for the reconstruction of US FDA drug- target network and theoretical-experimental studies of inhibitors of rasagiline derivatives for AChE.

    PubMed

    Prado-Prado, Francisco; García-Mera, Xerardo; Escobar, Manuel; Alonso, Nerea; Caamaño, Olga; Yañez, Matilde; González-Díaz, Humberto

    2012-01-01

    The number of neurodegenerative diseases has been increasing in recent years. Many of the drug candidates to be used in the treatment of neurodegenerative diseases present specific 3D structural features. An important protein in this sense is the acetylcholinesterase (AChE), which is the target of many Alzheimer's dementia drugs. Consequently, the prediction of Drug-Protein Interactions (DPIs/nDPIs) between new drug candidates and specific 3D structure and targets is of major importance. To this end, we can use Quantitative Structure-Activity Relationships (QSAR) models to carry out a rational DPIs prediction. Unfortunately, many previous QSAR models developed to predict DPIs take into consideration only 2D structural information and codify the activity against only one target. To solve this problem we can develop some 3D multi-target QSAR (3D mt-QSAR) models. In this study, using the 3D MI-DRAGON technique, we have introduced a new predictor for DPIs based on two different well-known software. We have used the MARCH-INSIDE (MI) and DRAGON software to calculate 3D structural parameters for drugs and targets respectively. Both classes of 3D parameters were used as input to train Artificial Neuronal Network (ANN) algorithms using as benchmark dataset the complex network (CN) made up of all DPIs between US FDA approved drugs and their targets. The entire dataset was downloaded from the DrugBank database. The best 3D mt-QSAR predictor found was an ANN of Multi-Layer Perceptron-type (MLP) with profile MLP 37:37-24-1:1. This MLP classifies correctly 274 out of 321 DPIs (Sensitivity = 85.35%) and 1041 out of 1190 nDPIs (Specificity = 87.48%), corresponding to training Accuracy = 87.03%. We have validated the model with external predicting series with Sensitivity = 84.16% (542/644 DPIs; Specificity = 87.51% (2039/2330 nDPIs) and Accuracy = 86.78%. The new CNs of DPIs reconstructed from US FDA can be used to explore large DPI databases in order to discover both new drugs

  9. The Community College Foundation Today: A. History, Characteristics, and Assets.

    ERIC Educational Resources Information Center

    Angel, Dan; Gares, Dale

    1989-01-01

    Offers a historical perspective on the community college foundation, reviews 1987 research findings concerning foundation assets, lists 10 steps to establishing a foundation, and identifies key factors in organizational success. Describes the revitalization of the Citrus College Foundation. (DMM)

  10. α6 nAChR subunit residues that confer α-conotoxin BuIA selectivity.

    PubMed

    Kim, Hyun-Woo; McIntosh, J Michael

    2012-10-01

    Nicotinic acetylcholine receptors (nAChRs) containing α6 and/or α4 subunits modulate the release of dopamine. However, few compounds can effectively discriminate between ligand-binding sites that contain α6 vs. α4 nAChR subunits. Using a chimeric (α6/α4) subunit, we showed that α-conotoxin BuIA binds the extracellular rat α6β2 vs. α4β2 interface with ∼60,000-fold selectivity. Chimeras containing residues from the α6 subunit were inserted into the homologous position of the α4 subunit to identify critical sequence segments. The region between residues 184 and 207 in the α6 subunit accounted for the potency difference. Chimeras within this region followed by point mutations were constructed for further definition. α6 Lys185, Thr187, and Ile188 form a triad of key residues that influence BuIA binding; when these 3 α6 residues were inserted into the α4 subunit, there was an ∼2000-fold increase in toxin potency. We used a crystal structure of BuIA bound to the acetylcholine-binding protein together with the structure of the Torepedo marmorata nAChR to build a homology model of BuIA bound to the interface between α6 and β2 subunits. The results indicate that the triad of α6 residues lies outside the C loop and is distantly located from bound BuIA (>10 Å). This suggests that alterations in potency are not caused by the direct interaction between the triad and BuIA. Instead, alterations in C-loop 3-dimensional structure and/or flexibility may account for differential potency. Thr198 and Tyr205 also contributed to BuIA potency. In addition, Thr198 caused BuIA potency differences between the closely related α6 and α3 subunits. Together, the findings provide insight into differences between the α6 and other α subunits that may be exploited by α-conotoxins to achieve binding selectivity. PMID:22751014

  11. Textural break foundation wall construction modules

    DOEpatents

    Phillips, Steven J.

    1990-01-01

    Below-grade, textural-break foundation wall structures are provided for inhibiting diffusion and advection of liquids and gases into and out from a surrounding hydrogeologic environment. The foundation wall structure includes a foundation wall having an interior and exterior surface and a porous medium disposed around a portion of the exterior surface. The structure further includes a modular barrier disposed around a portion of the porous medium. The modular barrier is substantially removable from the hydrogeologic environment.

  12. Mathematical foundation of quantum annealing

    SciTech Connect

    Morita, Satoshi; Nishimori, Hidetoshi

    2008-12-15

    Quantum annealing is a generic name of quantum algorithms that use quantum-mechanical fluctuations to search for the solution of an optimization problem. It shares the basic idea with quantum adiabatic evolution studied actively in quantum computation. The present paper reviews the mathematical and theoretical foundations of quantum annealing. In particular, theorems are presented for convergence conditions of quantum annealing to the target optimal state after an infinite-time evolution following the Schroedinger or stochastic (Monte Carlo) dynamics. It is proved that the same asymptotic behavior of the control parameter guarantees convergence for both the Schroedinger dynamics and the stochastic dynamics in spite of the essential difference of these two types of dynamics. Also described are the prescriptions to reduce errors in the final approximate solution obtained after a long but finite dynamical evolution of quantum annealing. It is shown there that we can reduce errors significantly by an ingenious choice of annealing schedule (time dependence of the control parameter) without compromising computational complexity qualitatively. A review is given on the derivation of the convergence condition for classical simulated annealing from the view point of quantum adiabaticity using a classical-quantum mapping.

  13. Evolutionary foundations for cancer biology

    PubMed Central

    Aktipis, C Athena; Nesse, Randolph M

    2013-01-01

    New applications of evolutionary biology are transforming our understanding of cancer. The articles in this special issue provide many specific examples, such as microorganisms inducing cancers, the significance of within-tumor heterogeneity, and the possibility that lower dose chemotherapy may sometimes promote longer survival. Underlying these specific advances is a large-scale transformation, as cancer research incorporates evolutionary methods into its toolkit, and asks new evolutionary questions about why we are vulnerable to cancer. Evolution explains why cancer exists at all, how neoplasms grow, why cancer is remarkably rare, and why it occurs despite powerful cancer suppression mechanisms. Cancer exists because of somatic selection; mutations in somatic cells result in some dividing faster than others, in some cases generating neoplasms. Neoplasms grow, or do not, in complex cellular ecosystems. Cancer is relatively rare because of natural selection; our genomes were derived disproportionally from individuals with effective mechanisms for suppressing cancer. Cancer occurs nonetheless for the same six evolutionary reasons that explain why we remain vulnerable to other diseases. These four principles—cancers evolve by somatic selection, neoplasms grow in complex ecosystems, natural selection has shaped powerful cancer defenses, and the limitations of those defenses have evolutionary explanations—provide a foundation for understanding, preventing, and treating cancer. PMID:23396885

  14. From the Cajal alumni Achúcarro and Río-Hortega to the rediscovery of never-resting microglia

    PubMed Central

    Tremblay, Marie-Ève; Lecours, Cynthia; Samson, Louis; Sánchez-Zafra, Víctor; Sierra, Amanda

    2015-01-01

    Under the guidance of Ramón y Cajal, a plethora of students flourished and began to apply his silver impregnation methods to study brain cells other than neurons: the neuroglia. In the first decades of the twentieth century, Nicolás Achúcarro was one of the first researchers to visualize the brain cells with phagocytic capacity that we know today as microglia. Later, his pupil Pío del Río-Hortega developed modifications of Achúcarro's methods and was able to specifically observe the fine morphological intricacies of microglia. These findings contradicted Cajal's own views on cells that he thought belonged to the same class as oligodendroglia (the so called “third element” of the nervous system), leading to a long-standing discussion. It was only in 1924 that Río-Hortega's observations prevailed worldwide, thus recognizing microglia as a unique cell type. This late landing in the Neuroscience arena still has repercussions in the twenty first century, as microglia remain one of the least understood cell populations of the healthy brain. For decades, microglia in normal, physiological conditions in the adult brain were considered to be merely “resting,” and their contribution as “activated” cells to the neuroinflammatory response in pathological conditions mostly detrimental. It was not until microglia were imaged in real time in the intact brain using two-photon in vivo imaging that the extreme motility of their fine processes was revealed. These findings led to a conceptual revolution in the field: “resting” microglia are constantly surveying the brain parenchyma in normal physiological conditions. Today, following Cajal's school of thought, structural and functional investigations of microglial morphology, dynamics, and relationships with neurons and other glial cells are experiencing a renaissance and we stand at the brink of discovering new roles for these unique immune cells in the healthy brain, an essential step to understand their

  15. Contributions of β2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice

    PubMed Central

    Cole, Robert D.; Poole, Rachel L.; Guzman, Dawn M.; Gould, Thomas J.; Parikh, Vinay

    2014-01-01

    Rationale Deficits in executive functions underlie compulsive drug use and understanding how nicotine influences these cognitive processes may provide important information on neurobiological substrates of nicotine addiction. Accumulating evidence suggests that β2 subunit-containing nicotinic receptors (nAChRs) are involved in the reinforcing process of nicotine addiction. Whether these nAChRs also contributes to the detrimental effects of chronic nicotine on flexible decision-making is not known. Objectives In the present study, the effects of chronic nicotine were assessed in mice with partial or complete deletion of the β2-subunit containing nAChR gene (β2+/- or β2-/-) performing an operant cognitive flexibility task. Results Visual discrimination learning was not affected in saline-treated β2 nAChR mutants as compared to the wild-type (β2+/+) mice; yet, chronic nicotine facilitated acquisition of visual discrimination in all genotypes. The acquisition of new egocentric response strategy set-shifting remained similar in all genotypes and there was no effect of treatment. Chronic nicotine treatment impaired reversal learning in β2+/+ mice by increasing response perseveration to the previously rewarded stimulus. Moreover, the acquisition of inverted stimulus-reward contingencies did not differ between β2+/+ and β2-/- mice exposed to chronic nicotine. Interestingly, nicotine-induced reversal learning deficits were not observed in β2+/- mice. Conclusions Collectively, these findings suggest that β2 subunit-containing nAChRs are not critical for visual discrimination learning and extradimensional rule shift. However, sustained activation of these nAChRs with nicotine may interfere with inhibitory control processes influencing affective shifts in stimulus-reward contingencies. PMID:25281224

  16. Foundations and Higher Education: Whose Agenda?

    ERIC Educational Resources Information Center

    Schneider, John C.

    2007-01-01

    Grant programs that had been relatively open-ended were now tightly drawn, grounded in the foundations' own carefully articulated take on issues and receptive only to proposals that responded appropriately. Initiative and creativity had shifted heavily from prospective grantee to grantor. As foundations embraced this funding-by-agenda, it burdened…

  17. Liberating Foundations of Art and Design

    ERIC Educational Resources Information Center

    Lerner, Fern

    2012-01-01

    Research concerning the basic course known as Foundations of Art and Design strengthens the pedagogical approach for K-16 art and design education. The version of Foundations introduced to America by Josef Albers, although hardly changed, is shown to have continued, timeless relevance. Next, a sequential, implicit logic is revealed in linking the…

  18. Bernard van Leer Foundation Annual Report, 2001.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This annual report for 2001 describes the year's activities, achievements, and financial status of the Bernard van Leer Foundation, a private foundation based in The Netherlands operating internationally to improve opportunities for young children from birth to age 7 living in circumstances of social and economic disadvantage. Following the…

  19. Bernard van Leer Foundation Annual Report 1998.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This document provides an annual report and financial review for 1998 of the Bernard van Leer Foundation, a private institution created in 1949 for broad humanitarian purposes. Following an introduction by chairman of the Foundation's board of trustees, a report of the executive director details the second year of implementation of the…

  20. Bernard van Leer Foundation Annual Report, 2000.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This annual report for 2000 describes the year's activities, achievements, and financial status of the Bernard van Leer Foundation, a private foundation based in The Netherlands that operates internationally to improve opportunities for young children from birth to age 7 living in circumstances of social and economic disadvantage. Following an…

  1. Bernard van Leer Foundation Annual Report, 2002.

    ERIC Educational Resources Information Center

    Bernard Van Leer Foundation, The Hague (Netherlands).

    This annual report for 2002 describes the year's activities, achievements, and financial status of the Bernard van Leer Foundation, a private foundation based in The Netherlands operating internationally to improve opportunities for young children from birth to age 7 living in circumstances of social and economic disadvantage. Following the…

  2. Inter-American Foundation Annual Report 1987.

    ERIC Educational Resources Information Center

    Inter-American Foundation, Rosslyn, VA.

    This annual report from the Inter-American Foundation (IAF), a federal development agency, includes letters from foundation officials describing the IAF-funded work in poverty areas of Latin America and the Caribbean. The report describes IAF's In-Country Support System (ICS), staffed by local professionals who assist grantees and report their…

  3. Peace Education: Exploring Some Philosophical Foundations

    ERIC Educational Resources Information Center

    Page, James S.

    2004-01-01

    Peace education has been recognized as an important aspect of social education for the past three decades. The critical literature as well as official documents, however, have given little attention to its philosophical foundations. This essay explores these foundations in the ethics of (1) virtue, (2) consequentialism, (3) aesthetics, (4)…

  4. Support for Science from a Foundation Perspective.

    ERIC Educational Resources Information Center

    Finberg, Barbara D.

    1990-01-01

    Presents examples of unique contributions of individuals at private foundations to the emergence and growth of scientific research on child and adolescent development. Discusses specific leaders of the Carnegie Foundation and the Laura Spelman Rockefeller Memorial Fund to demonstrate how influential individuals can be in determining major…

  5. Foundations of Education: Texts and the Canon.

    ERIC Educational Resources Information Center

    Gottlieb, Esther E.

    This paper attempts to outline the textual canon of the foundations of education in U.S. teacher education programs. Background research for the project included a review of selected texts and samples of course syllabi. Analysis of the contents and prefaces of the two volumes of "Reading in the Foundations of Education" (published in 1941 by…

  6. Kellogg Foundation Still Investing in People

    ERIC Educational Resources Information Center

    Abdul-Alim, Jamaal

    2011-01-01

    When the W.K. Kellogg Foundation first approached a group of tribal college presidents in 1994 with a $23 million grant for a handful of their institutions, the tribal college leaders did not exactly trip over themselves to get the money. They wanted it to be split among all of them, and the foundation honored the tribal college leaders' wish.…

  7. On the Need to Live Educational Foundations

    ERIC Educational Resources Information Center

    Schubert, William H.

    2013-01-01

    William H. Schubert, retired faculty member at the University of Illinois, Chicago, reflects on his teaching career and the loss of "educational foundations." Schubert states that "Foundations of Education" are being pushed toward the precipice of extinction. He describes a loss of "back-to-basics" education with a…

  8. Energy foundations for sustainable development

    SciTech Connect

    Sather, N.F.

    1992-01-01

    Worldwide, more than three-quarters of our energy needs are obtained from nonrenewable reserves of coal, oil, gas, and uranium. The unavoidable outcome of our present path is the depletion of all non-renewable energy resources. Further exacerbating the energy picture is the mounting cost of mitigating the adverse environmental and health impacts of energy use. Problems ranging from acid rain and radioactive waste storage to the potential for widespread environmental disaster that could result from the buildup of greenhouse gases in the atmosphere have made it that the earth's capacity to absorb the waste products of energy use without serious consequences is being severely strained. Potential supply shortages and mounting costs for the energy component of our industrial enterprise will increasingly undermine our ability to sustain global economic development. Strong positive actions that shore up the energy foundations of our economy arc called for. The purpose of this presentation is to focus attention on two such proactive steps which, though insufficient to the task by themselves, are nevertheless crucial to any effective plan for heading off the recessionary tendencies of our growing energy supply and cost dilemma. The first of these essential steps is to develop a much better arrangement than we currently have for including all costs for the adverse health and environmental impacts of industrial production in the price paid by consumers for fuels, electricity, and manufactured goods. The second essential action is to expand our R D effort to develop new manufacturing processes and new materials and products that meet our needs for power, fuels and consumer goods at lower cost, greater efficiency, and with reduced environmental cost.

  9. Energy foundations for sustainable development

    SciTech Connect

    Sather, N.F.

    1992-09-01

    Worldwide, more than three-quarters of our energy needs are obtained from nonrenewable reserves of coal, oil, gas, and uranium. The unavoidable outcome of our present path is the depletion of all non-renewable energy resources. Further exacerbating the energy picture is the mounting cost of mitigating the adverse environmental and health impacts of energy use. Problems ranging from acid rain and radioactive waste storage to the potential for widespread environmental disaster that could result from the buildup of greenhouse gases in the atmosphere have made it that the earth`s capacity to absorb the waste products of energy use without serious consequences is being severely strained. Potential supply shortages and mounting costs for the energy component of our industrial enterprise will increasingly undermine our ability to sustain global economic development. Strong positive actions that shore up the energy foundations of our economy arc called for. The purpose of this presentation is to focus attention on two such proactive steps which, though insufficient to the task by themselves, are nevertheless crucial to any effective plan for heading off the recessionary tendencies of our growing energy supply and cost dilemma. The first of these essential steps is to develop a much better arrangement than we currently have for including all costs for the adverse health and environmental impacts of industrial production in the price paid by consumers for fuels, electricity, and manufactured goods. The second essential action is to expand our R&D effort to develop new manufacturing processes and new materials and products that meet our needs for power, fuels and consumer goods at lower cost, greater efficiency, and with reduced environmental cost.

  10. Density functional theory: Foundations reviewed

    NASA Astrophysics Data System (ADS)

    Kryachko, Eugene S.; Ludeña, Eduardo V.

    2014-11-01

    Guided by the above motto (quotation), we review a broad range of issues lying at the foundations of Density Functional Theory, DFT, a theory which is currently omnipresent in our everyday computational study of atoms and molecules, solids and nano-materials, and which lies at the heart of modern many-body computational technologies. The key goal is to demonstrate that there are definitely the ways to improve DFT. We start by considering DFT in the larger context provided by reduced density matrix theory (RDMT) and natural orbital functional theory (NOFT), and examine the implications that N-representability conditions on the second-order reduced density matrix (2-RDM) have not only on RDMT and NOFT but, also, by extension, on the functionals of DFT. This examination is timely in view of the fact that necessary and sufficient N-representability conditions on the 2-RDM have recently been attained. In the second place, we review some problems appearing in the original formulation of the first Hohenberg-Kohn theorem which is still a subject of some controversy. In this vein we recall Lieb's comment on this proof and the extension to this proof given by Pino et al. (2009), and in this context examine the conditions that must be met in order that the one-to-one correspondence between ground-state densities and external potentials remains valid for finite subspaces (namely, the subspaces where all Kohn-Sham solutions are obtained in practical applications). We also consider the issue of whether the Kohn-Sham equations can be derived from basic principles or whether they are postulated. We examine this problem in relation to ab initio DFT. The possibility of postulating arbitrary Kohn-Sham-type equations, where the effective potential is by definition some arbitrary mixture of local and non-local terms, is discussed. We also deal with the issue of whether there exists a universal functional, or whether one should advocate instead the construction of problem

  11. The Foundation-Institution Partnership: The Role of Institutionally Related Foundations in Public Higher Education

    ERIC Educational Resources Information Center

    Bass, David

    2010-01-01

    Institutionally related foundations have played a vital role in raising and managing private resources in support of public institutions of higher education. Unlike private grant-making foundations, college and university foundations are typically incorporated as public charities under section 501(c)(3) of the Internal Revenue Code. Although they…

  12. Density functional theory: Foundations reviewed

    NASA Astrophysics Data System (ADS)

    Kryachko, Eugene S.; Ludeña, Eduardo V.

    2014-11-01

    Guided by the above motto (quotation), we review a broad range of issues lying at the foundations of Density Functional Theory, DFT, a theory which is currently omnipresent in our everyday computational study of atoms and molecules, solids and nano-materials, and which lies at the heart of modern many-body computational technologies. The key goal is to demonstrate that there are definitely the ways to improve DFT. We start by considering DFT in the larger context provided by reduced density matrix theory (RDMT) and natural orbital functional theory (NOFT), and examine the implications that N-representability conditions on the second-order reduced density matrix (2-RDM) have not only on RDMT and NOFT but, also, by extension, on the functionals of DFT. This examination is timely in view of the fact that necessary and sufficient N-representability conditions on the 2-RDM have recently been attained. In the second place, we review some problems appearing in the original formulation of the first Hohenberg-Kohn theorem which is still a subject of some controversy. In this vein we recall Lieb's comment on this proof and the extension to this proof given by Pino et al. (2009), and in this context examine the conditions that must be met in order that the one-to-one correspondence between ground-state densities and external potentials remains valid for finite subspaces (namely, the subspaces where all Kohn-Sham solutions are obtained in practical applications). We also consider the issue of whether the Kohn-Sham equations can be derived from basic principles or whether they are postulated. We examine this problem in relation to ab initio DFT. The possibility of postulating arbitrary Kohn-Sham-type equations, where the effective potential is by definition some arbitrary mixture of local and non-local terms, is discussed. We also deal with the issue of whether there exists a universal functional, or whether one should advocate instead the construction of problem

  13. Activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) reverses referred mechanical hyperalgesia induced by colonic inflammation in mice.

    PubMed

    Costa, Robson; Motta, Emerson M; Manjavachi, Marianne N; Cola, Maíra; Calixto, João B

    2012-10-01

    In the current study, we investigated the effect of the activation of the alpha-7 nicotinic acetylcholine receptor (α7 nAchR) on dextran sulphate sodium (DSS)-induced colitis and referred mechanical hyperalgesia in mice. Colitis was induced in CD1 male mice through the intake of 4% DSS in tap water for 7 days. Control mice received unadulterated water. Referred mechanical hyperalgesia was evaluated for 7 days after the beginning of 4% DSS intake. Referred mechanical hyperalgesia started within 1 day after beginning DSS drinking, peaked at 3 days and persisted for 7 days. This time course profile perfectly matched with the appearance of signs of colitis. Both acute and chronic oral treatments with nicotine (0.1-1.0 mg/kg, p.o.) were effective in inhibiting the established referred mechanical hyperalgesia. The antinociceptive effect of nicotine was completely abrogated by cotreatment with the selective α7 nAchR antagonist methyllycaconitine (MLA) (1.0 mg/kg). Consistent with these results, i.p. treatment with the selective α7 nAchR agonist PNU 282987 (0.1-1.0 mg/kg) reduced referred mechanical hyperalgesia at all periods of evaluation. Despite their antinociceptive effects, nicotinic agonists did not affect DSS-induced colonic damage or inflammation. Taken together, the data generated in the present study show the potential relevance of using α7 nAchR agonists to treat referred pain and discomfort associated with inflammatory bowel diseases.

  14. Characterization of a T-superfamily conotoxin TxVC from Conus textile that selectively targets neuronal nAChR subtypes.

    PubMed

    Wang, Shuo; Du, Tianpeng; Liu, Zhuguo; Wang, Sheng; Wu, Ying; Ding, Jiuping; Jiang, Ling; Dai, Qiuyun

    2014-11-01

    T-superfamily conotoxins have a typical cysteine pattern of "CC-CC", and are known to mainly target calcium or sodium ion channels. Recently, we screened the targets of a series of T-superfamily conotoxins and found that a new T-superfamily conotoxin TxVC (KPCCSIHDNSCCGL-NH2) from the venom of Conus textile. It selectively targeted the neuronal nicotinic acetylcholine receptor (nAChR) subtypes α4β2 and α3β2, with IC50 values of 343.4 and 1047.2nM, respectively, but did not exhibit obvious pharmacological effects on voltage-gated potassium, sodium or calcium channel in DRG cells, the BK channels expressed in HEK293 cells, or the Kv channels in LβT2 cells. The changes in the inhibitory activities of its Ala mutants, the NMR structure, and molecular simulation results based on other conotoxins targeting nAChR α4β2, all demonstrated that the residues Ile(6) and Leu(14) were the main hydrophobic pharmacophores. To our best knowledge, this is the first T-superfamily conotoxin that inhibits neuronal nAChRs and possesses high binding affinity to α4β2. This finding will expand the knowledge of the targets of T-superfamily conotoxins and the motif information could help the design of new nAChR inhibitors.

  15. Electrical and Optical Properties of Si-Incorporated a-C:H Films via the Radio Frequency Plasma-Enhanced Chemical Vapor Deposition Method.

    PubMed

    Kim, In Jun; Choi, Won Seok; Hong, Byungyou

    2016-05-01

    The optical and electrical properties of silicon-incorporated hydrogenated amorphous carbon (a-C:H:Si) films deposited via the radio frequency (RF) plasma-enhanced chemical vapor deposition (PECVD) method using a mixture of CH4, H2, and SiH4 were observed. The silane gas whose ranged from 0 to 25 vol.% [SiH4/(SiH4 + CH4) was fed into the reactor while the other deposition parameters were kept constant. The basic properties of these films were investigated via Raman spectroscopy, UV-visible spectrometry, I-V measurement, and surface profiling. The experiment results showed that the film thickness increased from 300 nm to 800 nm for the same deposition time as the silane gas increased. The Raman spectrum obtained from the silicon-incorporated a-C:H films suggested that the film property changed from graphitic-like to more diamond-like. As the silane gas increased, the optical gap, E04, slightly increased from 1.98 eV to 2.62 eV. It was shown that the Si atoms incorporated into the a-C:H films reduced the size of the sp2 clusters. As for the I-V characteristics, the Si-incorporated a-C:H films had a lower leakage current than the a-C:H films without Si. PMID:27483937

  16. Notes on three new immigrant species of spilanthes jacq. (Asteraceae) in India and the identity of the common 'tooth - ache plant'.

    PubMed

    Sivarajan, V V; Mathew, P

    1984-01-01

    Three new immigrant species of Spilanthes Jacq. (Asteraceae) is described for the first time from India. Their current nomenclature and an artificial key for the identification of the 5 Indian species are provided. The identity of the commonly used 'tooth-ache' plant is also discussed. PMID:22557401

  17. Sharing the Vision, Leading the Way: Continuing Educators in the New Millennium. ACHE Proceedings (62nd, Myrtle Beach, South Carolina, October 14-17, 2000).

    ERIC Educational Resources Information Center

    Barrineau, Irene T., Ed.

    This document presents the proceedings of the 2000 annual meeting of the Association for Continuing Higher Education (ACHE). Part 1 contains the text of the presidential address, "Building Solid Communities within Higher Education" (Nancy Thomason), as well as summaries of the following addresses: "Riding the Rapids of Change: Survival Tactics for…

  18. Seismic isolation of two dimensional periodic foundations

    SciTech Connect

    Yan, Y.; Mo, Y. L.; Laskar, A.; Cheng, Z.; Shi, Z.; Menq, F.; Tang, Y.

    2014-07-28

    Phononic crystal is now used to control acoustic waves. When the crystal goes to a larger scale, it is called periodic structure. The band gaps of the periodic structure can be reduced to range from 0.5 Hz to 50 Hz. Therefore, the periodic structure has potential applications in seismic wave reflection. In civil engineering, the periodic structure can be served as the foundation of upper structure. This type of foundation consisting of periodic structure is called periodic foundation. When the frequency of seismic waves falls into the band gaps of the periodic foundation, the seismic wave can be blocked. Field experiments of a scaled two dimensional (2D) periodic foundation with an upper structure were conducted to verify the band gap effects. Test results showed the 2D periodic foundation can effectively reduce the response of the upper structure for excitations with frequencies within the frequency band gaps. When the experimental and the finite element analysis results are compared, they agree well with each other, indicating that 2D periodic foundation is a feasible way of reducing seismic vibrations.

  19. Foundations for a theory of gravitation theories

    NASA Technical Reports Server (NTRS)

    Thorne, K. S.; Lee, D. L.; Lightman, A. P.

    1972-01-01

    A foundation is laid for future analyses of gravitation theories. This foundation is applicable to any theory formulated in terms of geometric objects defined on a 4-dimensional spacetime manifold. The foundation consists of (1) a glossary of fundamental concepts; (2) a theorem that delineates the overlap between Lagrangian-based theories and metric theories; (3) a conjecture (due to Schiff) that the Weak Equivalence Principle implies the Einstein Equivalence Principle; and (4) a plausibility argument supporting this conjecture for the special case of relativistic, Lagrangian-based theories.

  20. Relativistic Navigation: A Theoretical Foundation

    NASA Technical Reports Server (NTRS)

    Turyshev, Slava G.

    1996-01-01

    We present a theoretical foundation for relativistic astronomical measurements in curved space-time. In particular, we discuss a new iterative approach for describing the dynamics of an isolated astronomical N-body system in metric theories of gravity. To do this, we generalize the Fock-Chandrasekhar method of the weak-field and slow-motion approximation (WFSMA) and develop a theory of relativistic reference frames (RF's) for a gravitationally bounded many-extended-body problem. In any proper RF constructed in the immediate vicinity of an arbitrary body, the N-body solutions of the gravitational field equations are formally presented as a sum of the Riemann-flat inertial space-time, the gravitational field generated by the body itself, the unperturbed solutions for each body in the system transformed to the coordinates of this proper RF, and the gravitational interaction term. We develop the basic concept of a general WFSMA theory of the celestial RF's applicable to a wide class of metric theories of gravity and an arbitrary model of matter distribution. We apply the proposed method to general relativity. Celestial bodies are described using a perfect fluid model; as such, they possess any number of internal mass and current multipole moments that explicitly characterize their internal structures. The obtained relativistic corrections to the geodetic equations of motion arise because of a coupling of the bodies' multiple moments to the surrounding gravitational field. The resulting relativistic transformations between the different RF's extend the Poincare group to the motion of deformable self-gravitating bodies. Within the present accuracy of astronomical measurements we discuss the properties of the Fermi-normal-like proper RF that is defined in the immediate vicinity of the extended compact bodies. We further generalize the proposed approximation method and include two Eddington parameters (gamma, Beta). This generalized approach was used to derive the

  1. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    SciTech Connect

    Machaalani, R.; Ghazavi, E.; Hinton, T.; Waters, K.A.; Hennessy, A.

    2014-05-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

  2. Pharmacological stress is required for the anti-alcohol effect of the α3β4* nAChR partial agonist AT-1001.

    PubMed

    Cippitelli, Andrea; Brunori, Gloria; Gaiolini, Kelly A; Zaveri, Nurulain T; Toll, Lawrence

    2015-06-01

    Alcohol and nicotine are often taken together. The mechanisms underlying this frequent co-abuse are not well known. Genetic and pharmacological evidence suggests that the nicotinic acetylcholine receptors (nAChRs) containing the α3 and β4 subunits play a role in alcohol as well as nicotine addiction. AT-1001 is a high affinity α3β4 nAChR partial agonist recently found to block nicotine self-administration and relapse-like behavior in rats. Here, to study the involvement of α3β4 nAChRs in the mechanisms that regulate alcohol abuse we evaluated the effects of AT-1001 on alcohol taking and seeking in Sprague-Dawley rats. AT-1001 reduced operant alcohol self-administration at the highest dose examined (3.0 mg/kg), an effect also observed for food self-administration. A dose of 1.5 mg/kg AT-1001, which had no effect on alcohol or food self-administration, essentially eliminated reinstatement of alcohol seeking induced by yohimbine (0.625 mg/kg) whereas, reinstatement induced by alcohol-associated cues was not altered, nor did AT-1001 induce reinstatement of extinguished self-administration on its own. Finally, AT-1001 showed an anxiolytic activity when measured in the presence or absence of yohimbine stress in the elevated plus maze paradigm. Together, these observations do not support a specific involvement of the α3β4 nAChR in mediating alcohol reward or cue-induced relapse to alcohol seeking but rather indicate that the α3β4 nAChR partial agonism may constitute an attractive approach for treating alcohol use disorders exacerbated by elevated stress response.

  3. Investigation of Acetylcholine Receptor Diversity in a Nematode Parasite Leads to Characterization of Tribendimidine- and Derquantel-Sensitive nAChRs

    PubMed Central

    Neveu, Cedric; Cabaret, Jacques; Cortet, Jacques; Peineau, Nicolas; Abongwa, Melanie; Courtot, Elise; Robertson, Alan P.; Martin, Richard J.

    2014-01-01

    Nicotinic acetylcholine receptors (nAChRs) of parasitic nematodes are required for body movement and are targets of important “classical” anthelmintics like levamisole and pyrantel, as well as “novel” anthelmintics like tribendimidine and derquantel. Four biophysical subtypes of nAChR have been observed electrophysiologically in body muscle of the nematode parasite Oesophagostomum dentatum, but their molecular basis was not understood. Additionally, loss of one of these subtypes (G 35 pS) was found to be associated with levamisole resistance. In the present study, we identified and expressed in Xenopus oocytes, four O. dentatum nAChR subunit genes, Ode-unc-38, Ode-unc-63, Ode-unc-29 and Ode-acr-8, to explore the origin of the receptor diversity. When different combinations of subunits were injected in Xenopus oocytes, we reconstituted and characterized four pharmacologically different types of nAChRs with different sensitivities to the cholinergic anthelmintics. Moreover, we demonstrate that the receptor diversity may be affected by the stoichiometric arrangement of the subunits. We show, for the first time, different combinations of subunits from a parasitic nematode that make up receptors sensitive to tribendimidine and derquantel. In addition, we report that the recombinant levamisole-sensitive receptor made up of Ode-UNC-29, Ode-UNC-63, Ode-UNC-38 and Ode-ACR-8 subunits has the same single-channel conductance, 35 pS and 2.4 ms mean open-time properties, as the levamisole-AChR (G35) subtype previously identified in vivo. These data highlight the flexible arrangements of the receptor subunits and their effects on sensitivity and resistance to the cholinergic anthelmintics; pyrantel, tribendimidine and/or derquantel may still be effective on levamisole-resistant worms. PMID:24497826

  4. Sudden Arrhythmia Death Syndromes (SADS) Foundation

    MedlinePlus

    ... SADS Foundation and John Hopkins Hospital Division of Cardiology are hosting a family support and educational meeting ... Baltimore/DC area families with cardiac arrhythmias. Sports Cardiology & Sudden Cardiac Arrest in the Young Conference 01/ ...

  5. Sartre: A Possible Foundation for Educational Theory.

    ERIC Educational Resources Information Center

    Burstow, Bonnie

    1983-01-01

    The claim by Khemais Benhamida and others that Jean-Paul Sartre's philosophy is too hostile and restrictive to serve as the foundation of progressive educational theory is based on an incomplete understanding of the philosopher's work. (IS)

  6. NCI collaborates with Multiple Myeloma Research Foundation

    Cancer.gov

    The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available datab

  7. Veatch's new foundation for medical ethics.

    PubMed

    Kultgen, J

    1985-11-01

    Robert M. Veatch proposes a "triple contract theory" as a new foundation for medical ethics. His criticisms of unilateral "physician ethics" are sound, but uncertainty as to whether he is proposing merely imaginary or real contracts vitiates his constructive arguments. If the former, he is recommending a minor heuristic device for thinking about ethics, not a foundation. If the latter, his proposal is utterly impractical and a medical covenant will have to be developed another way.

  8. Health legacy foundations: a new census.

    PubMed

    Niggel, Sabrina Jones; Brandon, William P

    2014-01-01

    Health care merger and acquisition activity has increased since enactment of the Affordable Care Act in 2010. Proceeds from transactions involving nonprofit hospitals, health systems, and health plans will endow philanthropic foundations, collectively known as health legacy foundations. Building on work by Grantmakers In Health, we undertook a systematic search for these foundations and generated a newly updated, comprehensive database. We found 306 organizations in forty-three states that have been endowed with proceeds from the sale, merger, lease, joint venture, or other restructuring of nonprofit health care assets. These health legacy foundations had $26.2 billion in assets in 2010. Concentrated in the southern United States, foundations originating from hospitals and specialty care facilities (86.6 percent) held mean assets of $64.7 million per funder and typically restricted grants to local communities. Foundations formed from health plans (13.4 percent) held higher mean assets ($222 million), usually served larger areas, and were more likely to engage in health care advocacy. Recent transactions involving smaller and stand-alone nonprofit hospitals will infuse many more communities with unprecedented charitable wealth.

  9. Health legacy foundations: a new census.

    PubMed

    Niggel, Sabrina Jones; Brandon, William P

    2014-01-01

    Health care merger and acquisition activity has increased since enactment of the Affordable Care Act in 2010. Proceeds from transactions involving nonprofit hospitals, health systems, and health plans will endow philanthropic foundations, collectively known as health legacy foundations. Building on work by Grantmakers In Health, we undertook a systematic search for these foundations and generated a newly updated, comprehensive database. We found 306 organizations in forty-three states that have been endowed with proceeds from the sale, merger, lease, joint venture, or other restructuring of nonprofit health care assets. These health legacy foundations had $26.2 billion in assets in 2010. Concentrated in the southern United States, foundations originating from hospitals and specialty care facilities (86.6 percent) held mean assets of $64.7 million per funder and typically restricted grants to local communities. Foundations formed from health plans (13.4 percent) held higher mean assets ($222 million), usually served larger areas, and were more likely to engage in health care advocacy. Recent transactions involving smaller and stand-alone nonprofit hospitals will infuse many more communities with unprecedented charitable wealth. PMID:24395949

  10. The foundation of self-esteem.

    PubMed

    Bailey, Joseph A

    2003-05-01

    Self-esteem is a simplistic term for varied and complex mental states pertaining to how one views oneself. It takes but little research in the voluminous literature to see the vagueness and inconsistencies in its various definitions. Even more problematic is the uncertainty concerning its foundational components. The importance of having a solid definition and specific ideas about the foundational components of self-esteem is that both pave the way to recognizing its causes; to predicting effects from those causes; and to organizing the trouble-shooting process for locating those philosophical flaws or psychological scars which lead to low self-esteem. The purpose of this paper is to offer a common ground for thinking about self-esteem at its most basic level. In order to distinguish the "basic level" from the rest of the components of self-esteem, let us liken it to a skyscraper building. Here, the focus is on the building's "underground foundation" and the base upon which that foundation rests. The base is a definition that allows for the assessment of the foundation. The underground foundation itself consists of the mental building blocks called self-meaning, self-identity, self-image, and self-concepts. To help illustrate their interactions, a few of the "masks" and "faces" of self-esteem will be mentioned. What is not being addressed is the "above ground structure"--those theories and manifestations dealt with by most mental health specialists.

  11. The foundation of self-esteem.

    PubMed Central

    Bailey, Joseph A.

    2003-01-01

    Self-esteem is a simplistic term for varied and complex mental states pertaining to how one views oneself. It takes but little research in the voluminous literature to see the vagueness and inconsistencies in its various definitions. Even more problematic is the uncertainty concerning its foundational components. The importance of having a solid definition and specific ideas about the foundational components of self-esteem is that both pave the way to recognizing its causes; to predicting effects from those causes; and to organizing the trouble-shooting process for locating those philosophical flaws or psychological scars which lead to low self-esteem. The purpose of this paper is to offer a common ground for thinking about self-esteem at its most basic level. In order to distinguish the "basic level" from the rest of the components of self-esteem, let us liken it to a skyscraper building. Here, the focus is on the building's "underground foundation" and the base upon which that foundation rests. The base is a definition that allows for the assessment of the foundation. The underground foundation itself consists of the mental building blocks called self-meaning, self-identity, self-image, and self-concepts. To help illustrate their interactions, a few of the "masks" and "faces" of self-esteem will be mentioned. What is not being addressed is the "above ground structure"--those theories and manifestations dealt with by most mental health specialists. PMID:12793795

  12. 75 FR 2844 - African Development Foundation, Board of Directors Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, January 26, 2010, 8:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  13. 75 FR 14418 - African Development Foundation, Board of Directors Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-25

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, April 13, 2010, 9:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  14. 75 FR 45600 - African Development Foundation, Board of Directors Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ...; ] AFRICAN DEVELOPMENT FOUNDATION African Development Foundation, Board of Directors Meeting Time: Tuesday, August 17, 2010, 8:30 a.m. to 1 p.m. Place: African Development Foundation, Conference Room, 1400...

  15. Evaluation of Z-(R,R)-IQNP for the potential imaging of m2 mAChR rich regions of the brain and heart.

    PubMed

    McPherson, D W; Greenbaum, M; Luo, H; Beets, A L; Knapp, F F

    2000-01-01

    Alterations in the function or density of the m2 muscarinic (mAChR) subtype have been postulated to play an important role in various dementias such as Alzheimer's disease. The ability to image and quantify the m2 mAChR subtype is of importance for a better understanding of the m2 subtype function in various dementias. Z-(R)-1-Azabicyclo[2.2.2]oct-3-y (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-(R,R)-IQNP) has demonstrated significant uptake in cerebral regions that contain a high concentration of m2 mAChR subtype in addition to heart tissue. The present study was undertaken to determine if the uptake of Z-(R,R)-IQNP in these regions is a receptor mediated process and to identify the radiospecies responsible for binding at the receptor site. A blocking study demonstrated cerebral and cardiac levels of activity were significantly reduced by pretreatment (2-3 mg/kg) of (R)-3-quinuclidinyl benzilate, dexetimide and scopolamine, established muscarinic antagonists. A direct comparison of the cerebral and cardiac uptake of [I-125]-Z-(R,R)-IQNP and [I-131]-E-(R,R)-IQNP (high uptake in ml, m4 rich mAChR cerebral regions) demonstrated Z-(R,R)-IQNP localized to a higher degree in cerebral and cardiac regions containing a high concentration of the m2 mAChR subtype as directly compared to E-(R,R)-IQNP. In addition, a study utilizing [I-123]-Z-(R,R)-IQNP, [I-131]-iododexetimide and [I-125]-R-3-quinuclidinyl S-4-iodobenzilate, Z-(R,R)-IQNP demonstrated significantly higher uptake and longer residence time in those regions which contain a high concentration of the m2 receptor subtype. Folch extraction of global brain and heart tissue at various times post injection of [I-125]-Z-(R,R)-IQNP demonstrated that approximately 80% of the activity was extracted in the lipid soluble fraction and identified as the parent ligand by TLC and HPLC analysis. These results demonstrate Z-(R,R)-IQNP has significant uptake, long residence time and high stability in

  16. The Foundation Programme in psychiatry: a qualitative study into the effects of a foundation placement

    PubMed Central

    Boyle, Ann; Davies, Sophie; Dogra, Nisha; Perry, Jennifer; Fosker, Hannah

    2016-01-01

    Aims and method There is a drive to increase the number of psychiatry foundation placements to ensure that training keeps up with the changing health and social care landscape. This qualitative study aimed to explore, by interview, the experiences of 17 doctors who have completed a foundation placement in psychiatry. Results The study highlights the benefits of foundation psychiatry placements and some of their positive and negative aspects. Clinical implications Those developing foundation placements will need to ensure they are of high quality. PMID:27752349

  17. Oooh, Your Aching Head!

    MedlinePlus

    ... RYE SIN-drome). previous continue When Should You Go to a Doctor? Headaches are very rarely a ... is particularly painful when a headache doesn't go away easily when a headache follows an injury, ...

  18. Orthopaedic research and education foundation and industry.

    PubMed

    Wurth, Gene R; Sherr, Judy H; Coffman, Thomas M

    2003-07-01

    Members of orthopaedic industry commit a significant amount of funds each year to support research and education programs that are directly related to their product(s). In addition, industry supports organizations such as the Orthopaedic Research and Education Foundation. The relationship between the Orthopaedic Research and Education Foundation and industry began in the early 1980s. The support to the Orthopaedic Research and Education Foundation from industry primarily has come in the form of unrestricted grants. These grants best can be looked at as an investment rather than a contribution. This form of giving, once called corporate philanthropy is more accurately referred to as strategic philanthropy. Members of industry make these investments to enhance their reputations, build brand awareness, market their products and services, improve employee morale, increase customer loyalty, and establish strategic alliances. The specialty of orthopaedics is among the leaders in medicine in the amount of funding raised within the specialty for research and education programs. This is because of the amount of support from members of industry and the surgeons. During the past 15 years, 40% of the annual support to the Orthopaedic Research and Education Foundation has come from industry and the balance has come from surgeons and members of lay public. Future industry support of the Orthopaedic Research and Education Foundation and other organizations within the specialty of orthopaedics will be dependent on the continued demonstration of tangible returns in areas described. PMID:12838052

  19. Impaired terrestrial and arboreal locomotor performance in the western fence lizard (Sceloporus occidentalis) after exposure to an AChE-inhibiting pesticide.

    PubMed

    DuRant, Sarah E; Hopkins, William A; Talent, Larry G

    2007-09-01

    We examined the effects of a commonly used AChE-inhibiting pesticide on terrestrial and arboreal sprint performance, important traits for predator avoidance and prey capture, in the western fence lizard (Sceloporus occidentalis). Lizards were exposed to carbaryl (2.5, 25, and 250 microg/g) and were raced before and 4, 24, and 96 h after dosing. In the terrestrial setting, exposure to low concentrations of carbaryl had stimulatory effects on performance, but exposure to the highest concentration was inhibitory. No stimulatory effects of carbaryl were noted in the arboreal environment and performance in lizards was reduced after exposure to both the medium and highest dose of carbaryl. Our findings suggest that acute exposure to high concentrations of carbaryl can have important sublethal consequences on fitness-related traits in reptiles and that arboreal locomotor performance is a more sensitive indicator of AChE-inhibiting pesticide poisoning than terrestrial locomotor performance. PMID:17360091

  20. The Frequency of Calcium Oscillations Induced by 5-HT, ACH, and KCl Determine the Contraction of Smooth Muscle Cells of Intrapulmonary Bronchioles

    PubMed Central

    Perez, Jose F.; Sanderson, Michael J.

    2005-01-01

    Increased resistance of airways or blood vessels within the lung is associated with asthma or pulmonary hypertension and results from contraction of smooth muscle cells (SMCs). To study the mechanisms regulating these contractions, we developed a mouse lung slice preparation containing bronchioles and arterioles and used phase-contrast and confocal microscopy to correlate the contractile responses with changes in [Ca2+]i of the SMCs. The airways are the focus of this study. The agonists, 5-hydroxytrypamine (5-HT) and acetylcholine (ACH) induced a concentration-dependent contraction of the airways. High concentrations of KCl induced twitching of the airway SMCs but had little effect on airway size. 5-HT and ACH induced asynchronous oscillations in [Ca2+]i that propagated as Ca2+ waves within the airway SMCs. The frequency of the Ca2+ oscillations was dependent on the agonist concentration and correlated with the extent of sustained airway contraction. In the absence of extracellular Ca2+ or in the presence of Ni2+, the frequency of the Ca2+ oscillations declined and the airway relaxed. By contrast, KCl induced low frequency Ca2+ oscillations that were associated with SMC twitching. Each KCl-induced Ca2+ oscillation consisted of a large Ca2+ wave that was preceded by multiple localized Ca2+ transients. KCl-induced responses were resistant to neurotransmitter blockers but were abolished by Ni2+ or nifedipine and the absence of extracellular Ca2+. Caffeine abolished the contractile effects of 5-HT, ACH, and KCl. These results indicate that (a) 5-HT and ACH induce airway SMC contraction by initiating Ca2+ oscillations, (b) KCl induces Ca2+ transients and twitching by overloading and releasing Ca2+ from intracellular stores, (c) a sustained, Ni2+-sensitive, influx of Ca2+ mediates the refilling of stores to maintain Ca2+ oscillations and, in turn, SMC contraction, and (d) the magnitude of sustained airway SMC contraction is regulated by the frequency of Ca2+ oscillations

  1. Queensland Emergency Medicine Research Foundation: special report.

    PubMed

    FitzGerald, Gerry; Codd, Catrina; Aitken, Peter; Sinnott, Michael

    2012-02-01

    Development of any new profession is dependent on the development of a special body of knowledge that is the domain of the profession. Key to this is research. Following sustained lobbying, the Queensland Government agreed to establish an emergency medicine research fund as part of an Enterprise Bargaining Agreement in 2006. That fund is managed by the Queensland Emergency Medicine Research Foundation. The present article describes the strategic approaches of the Foundation in its first 3 years, the application of research funds, and foreshadows an evaluative framework for determining the strategic value of this investment. The Foundation has developed a range of personnel and project support funding programmes, and competition for funding has increased. Ongoing evaluation will seek to determine the effectiveness of the current funding strategy on improving the effectiveness of research performance. It will also evaluate the clinical and organizational outcomes.

  2. Expert Meeting Report. Foundations Research Results

    SciTech Connect

    Ojczyk, C.; Huelman, P.; Carmody, J.

    2013-05-01

    The NorthernSTAR Building America Partnership held an expert meeting on Foundations–Research Results on November 15, 2011, in Minneapolis, MN. Audience participation was actively encouraged during each presentation to uncover needs and promote dialog among researchers and industry professionals. Key results were: greater understanding of the role of moisture transport through foundation and insulation materials and its potential impact on building durability; greater understanding of the role of foundation type in the process of selecting an insulation system for energy performance and building durability; need for research to quantify the risks associated with insulation processes to better enable users to weigh costs and benefits against the existing conditions of a home; need for improved performance modeling capabilities that address variations in foundation types and soil conditions.

  3. Analysis of foundations on reinforced soil

    NASA Astrophysics Data System (ADS)

    Brown, B. S.; Poulos, H. G.

    1980-10-01

    A finite element model of reinforced earth is used to investigate the increase in bearing capacity and stiffness of a foundation due to the placement of reinforcement in the soil. The analysis is used to examine the effect of reinforcement on the load settlement behavior of a strip foundation founded on a c-theta soil. It is shown that the improvement in foundation performance depends on both the number of reinforcing layers and on the concentration (surface area per unit width of footing) of the reinforcement. The case of a footing on a reinforced soil mass overlying a cavity or a very soft zone is also analyzed, and the reinforced soil is shown to result in a significant improvement in footing performance.

  4. Signature Pedagogies for Social Foundations: Negotiating Social Foundations Teaching Practices in the Field of Education

    ERIC Educational Resources Information Center

    Schneider, Sandra B.

    2010-01-01

    The conflicts arising between the pedagogical preferences of the fields of instructional design and technology (IDT) and social foundations of education are substantial. This conflict is primarily one of pedagogical values separating the Social Foundations with its emphasis on critical and creative thinking and the presumption of value and theory…

  5. Foundations for the Future: The Fundraising Role of Foundation Boards at Public Colleges and Universities

    ERIC Educational Resources Information Center

    Worth, Michael

    2012-01-01

    In the face of rising costs and a prolonged economic downturn, public colleges and universities are being challenged to increase their sources of private support and philanthropy. Drawing on the findings of a recent AGB survey of public college- and university-affiliated foundation board chairs and chief executive officers, Foundations for the…

  6. Effective Foundation Boards: A Guide for Members of Institutionally Related Foundation Boards

    ERIC Educational Resources Information Center

    Association of Governing Boards of Universities and Colleges, 2012

    2012-01-01

    Institutionally related foundations are an important partner to all institutions of public higher education. As public colleges, universities, and systems respond to a shifting landscape, related foundations have become increasingly important to their financial sustainability, commitment to academic access and educational excellence, and…

  7. Kellogg Foundation Initiative: Rewriting the Way Foundations Do Business in Indian Country.

    ERIC Educational Resources Information Center

    Boyer, Paul

    2000-01-01

    Describes the multi-million dollar initiative announced by W. K. Kellogg Foundation in 1995 to support the Native American Higher Education Initiative, and how the Kellogg initiative deserves attention from the nation as a whole because it is attempting to fundamentally rewrite the way foundations do business with Indian communities. (VWC)

  8. Enhancing the Reliability of GPCR Models by Accounting for Flexibility of Their Pro-Containing Helices: the Case of the Human mAChR1 Receptor.

    PubMed

    Pedretti, Alessandro; Mazzolari, Angelica; Ricci, Chiara; Vistoli, Giulio

    2015-04-01

    To better investigate the GPCR structures, we have recently proposed to explore their flexibility by simulating the bending of their Pro-containing TM helices so generating a set of models (the so-called chimeras) which exhaustively combine the two conformations (bent and straight) of these helices. The primary objective of the study is to investigate whether such an approach can be exploited to enhance the reliability of the GPCR models generated by distant templates. The study was focused on the human mAChR1 receptor for which a presumably reliable model was generated using the congener mAChR3 as the template along with a second less reliable model based on the distant β2-AR template. The second model was then utilized to produce the chimeras by combining the conformations of its Pro-containing helices (i.e., TM4, TM5, TM6 and TM7 with 16 modeled chimeras). The reliability of such chimeras was assessed by virtual screening campaigns as evaluated using a novel skewness metric where they surpassed the predictive power of the more reliable mAChR1 model. Finally, the virtual screening campaigns emphasize the opportunity of synergistically combining the scores of more chimeras using a specially developed tool which generates highly predictive consensus functions by maximizing the corresponding enrichment factors. PMID:27490167

  9. Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating.

    PubMed

    Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G

    2016-10-01

    We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating. PMID:27375219

  10. Mutations Causing Slow-Channel Myasthenia Reveal That a Valine Ring in the Channel Pore of Muscle AChR is Optimized for Stabilizing Channel Gating.

    PubMed

    Shen, Xin-Ming; Okuno, Tatsuya; Milone, Margherita; Otsuka, Kenji; Takahashi, Koji; Komaki, Hirofumi; Giles, Elizabeth; Ohno, Kinji; Engel, Andrew G

    2016-10-01

    We identify two novel mutations in acetylcholine receptor (AChR) causing a slow-channel congenital myasthenia syndrome (CMS) in three unrelated patients (Pts). Pt 1 harbors a heterozygous βV266A mutation (p.Val289Ala) in the second transmembrane domain (M2) of the AChR β subunit (CHRNB1). Pts 2 and 3 carry the same mutation at an equivalent site in the ε subunit (CHRNE), εV265A (p.Val285Ala). The mutant residues are conserved across all AChR subunits of all species and are components of a valine ring in the channel pore, which is positioned four residues above the leucine ring. Both βV266A and εV265A reduce the amino acid size and lengthen the channel opening bursts by fourfold by enhancing gating efficiency by approximately 30-fold. Substitution of alanine for valine at the corresponding position in the δ and α subunit prolongs the burst duration four- and eightfold, respectively. Replacing valine at ε codon 265 either by a still smaller glycine or by a larger leucine also lengthens the burst duration. Our analysis reveals that each valine in the valine ring contributes to channel kinetics equally, and the valine ring has been optimized in the course of evolution to govern channel gating.

  11. External-Field-Induced Growth Effect of an a-C:H Film for Manipulating Its Medium-Range Nanostructures and Properties.

    PubMed

    Song, Hui; Ji, Li; Li, Hongxuan; Liu, Xiaohong; Wang, Weiqi; Zhou, Huidi; Chen, Jianmin

    2016-03-01

    A special catalytic growth effect (called the "external-field-induced effect") was found to exist on the poisoning target surface during the reactive sputtering process of a-C:H films. Enlightened by this effect, we demonstrate a facile approach to manipulate the medium-range-ordered nanostructure and mechanical and tribological properties of a-C:H films. By adjusting the plasma ionization degree, a graphene precursor was successfully produced at the graphite target surface through the synergistic catalytic effects of both the catalyst and plasma. Then, graphene was further sputtered into amorphous carbon films to form graphene-like nanoclusters. This special graphene-like nanostructure endows the a-C:H film with outstanding hardness, high elasticity, and excellent tribological properties. The elastic recovery of the film was improved to 92.5%, and the wear life in a vacuum environment was also prolonged to 8.8 × 10(5) cycles at a contact stress of 0.9 GPa, which suggests that medium-range-ordered clusters in an amorphous carbon matrix provide an important way to improve the properties of carbon films. PMID:26895554

  12. Impairment of contextual fear extinction by chronic nicotine and withdrawal from chronic nicotine is associated with hippocampal nAChR upregulation.

    PubMed

    Kutlu, Munir Gunes; Oliver, Chicora; Huang, Peng; Liu-Chen, Lee-Yuan; Gould, Thomas J

    2016-10-01

    Chronic nicotine and withdrawal from chronic nicotine have been shown to be major modulators of fear learning behavior. Moreover, recent studies from our laboratory have shown that acute nicotine impaired fear extinction and safety learning in mice. However, the effects of chronic nicotine and withdrawal on fear extinction are unknown. Therefore, the current experiments were conducted to investigate the effects of chronic nicotine as well as withdrawal from chronic nicotine on contextual fear extinction in mice. C57BL6/J mice were given contextual fear conditioning training and retention testing during chronic nicotine administration. Mice then received contextual fear extinction either during chronic nicotine or during withdrawal from chronic nicotine. Our results showed that contextual fear extinction was impaired both during chronic nicotine administration and subsequent withdrawal. However, it was also observed that the effects of prior chronic nicotine disappeared after 72 h in withdrawal, a timeline that closely matches with the timing of the chronic nicotine-induced upregulation of hippocampal nicotinic acetylcholine receptor (nAChR) density. Additional experiments found that 4 days, but not 1 day, of continuous nicotine administration upregulated hippocampal nAChRs and impaired contextual fear extinction. These effects disappeared following 72 h withdrawal. Overall, these experiments provide a potential link between nicotine-induced upregulation of hippocampal nAChRs and fear extinction deficits observed in patients with anxiety disorders, which may lead to advancements in the pharmacological treatment methods for this disorder. PMID:27378334

  13. Philosophical foundations of respect for autonomy.

    PubMed

    Gauthier, C C

    1993-03-01

    Understanding the philosophical foundations of the principle of respect for autonomy is essential for its proper application within medical ethics. The foundations provided by Immanuel Kant's principle of humanity and John Stuart Mill's principle of liberty share substantial areas of agreement including: the grounding of respect for autonomy in the capacity for rational agency, the restriction of this principle to rational agents, and the important distinction between influence and control. Their work helps to clarify the scope and role of the principle of respect for autonomy in health care delivery; its implications for truth telling, informed consent, and confidentiality; and its relationship to other moral principles, such as beneficence and distributive justice.

  14. Peace Education: Exploring Some Philosophical Foundations

    NASA Astrophysics Data System (ADS)

    Page, James S.

    2004-01-01

    Peace education has been recognized as an important aspect of social education for the past three decades. The critical literature as well as official documents, however, have given little attention to its philosophical foundations. This essay explores these foundations in the ethics of (1) virtue, (2) consequentialism, (3) aesthetics, (4) conservative politics and (5) care. Each of these alone composes a significant element of peace education, although ultimately its solid basis can only be established through an integrative approach encouraging a culture of peace. The more complete development and articulation of the philosophical rationale of peace education is yet to be accomplished and remains a task for the future.

  15. 22 CFR 1502.3 - Access to Foundation records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Access to Foundation records. 1502.3 Section 1502.3 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.3 Access to Foundation records. Any person desiring to have access to Foundation records may call or apply in...

  16. 22 CFR 1502.3 - Access to Foundation records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Access to Foundation records. 1502.3 Section 1502.3 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.3 Access to Foundation records. Any person desiring to have access to Foundation records may call or apply in...

  17. 22 CFR 1502.3 - Access to Foundation records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Access to Foundation records. 1502.3 Section 1502.3 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.3 Access to Foundation records. Any person desiring to have access to Foundation records may call or apply in...

  18. 22 CFR 1002.3 - Access to Foundation records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Access to Foundation records. 1002.3 Section 1002.3 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.3 Access to Foundation records. Any person desiring to have access to Foundation records should call or apply in...

  19. 22 CFR 1002.3 - Access to Foundation records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Access to Foundation records. 1002.3 Section 1002.3 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.3 Access to Foundation records. Any person desiring to have access to Foundation records should call or apply in...

  20. 22 CFR 1002.3 - Access to Foundation records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Access to Foundation records. 1002.3 Section 1002.3 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.3 Access to Foundation records. Any person desiring to have access to Foundation records should call or apply in...

  1. 22 CFR 1502.3 - Access to Foundation records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Access to Foundation records. 1502.3 Section 1502.3 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.3 Access to Foundation records. Any person desiring to have access to Foundation records may call or apply in...

  2. 22 CFR 1002.3 - Access to Foundation records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Access to Foundation records. 1002.3 Section 1002.3 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.3 Access to Foundation records. Any person desiring to have access to Foundation records should call or apply in...

  3. 22 CFR 1002.3 - Access to Foundation records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Access to Foundation records. 1002.3 Section 1002.3 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.3 Access to Foundation records. Any person desiring to have access to Foundation records should call or apply in...

  4. 22 CFR 1502.3 - Access to Foundation records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Access to Foundation records. 1502.3 Section 1502.3 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.3 Access to Foundation records. Any person desiring to have access to Foundation records may call or apply in...

  5. National Science Foundation Annual Report 1989.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC.

    The report begins with a statement from the National Science Foundation (NSF) director, followed by a series of research notes summarizing research findings and results during the year 1989. Chapter 1, "Research Collaborations," describes some examples of the collaborations between universities, industry, and government in astronomy, atmospheric…

  6. Siemens Foundation and the STEM Challenge

    ERIC Educational Resources Information Center

    Harper-Taylor, Jeniffer

    2010-01-01

    For more than 12 years, the Siemens Foundation has found unique ways to partner with organizations to support educational initiatives in science, technology, engineering and mathematics (STEM) in the United States. Its focus is clear--to educate the next generation of innovators by supporting math and science education from grade school to grad…

  7. Excavationless Exterior Foundation Insulation Field Study

    SciTech Connect

    Schirber, T.; Mosiman, G.; Ojczyk, C.

    2014-10-01

    Building science research supports installing exterior (soil side) foundation insulation as the optimal method to enhance the hygrothermal performance of new homes. With exterior foundation insulation, water management strategies are maximized while insulating the basement space and ensuring a more even temperature at the foundation wall. However, such an approach can be very costly and disruptive when applied to an existing home, requiring deep excavation around the entire house. The NorthernSTAR Building America Partnership team implemented an innovative, minimally invasive foundation insulation upgrade technique on an existing home. The approach consisted of using hydrovac excavation technology combined with a liquid insulating foam. The team was able to excavate a continuous 4" wide by 4' to 5' deep trench around the entire house, 128 linear feet, except for one small part under the stoop that was obstructed with concrete debris. The combination pressure washer and vacuum extraction technology also enabled the elimination of large trenches and soil stockpiles normally produced by backhoe excavation. The resulting trench was filled with liquid insulating foam, which also served as a water-control layer of the assembly. The insulation was brought above grade using a liquid foam/rigid foam hybrid system and terminated at the top of the rim joist. Cost savings over the traditional excavation process ranged from 23% to 50%. The excavationless process could result in even greater savings since replacement of building structures, exterior features, utility meters, and landscaping would be minimal or non-existent in an excavationless process.

  8. Readiness, Behavior, and Foundational Mathematics Course Success

    ERIC Educational Resources Information Center

    Li, Kevin; Zelenka, Richard; Buonaguidi, Larry; Beckman, Robert; Casillas, Alex; Crouse, Jill; Allen, Jeff; Hanson, Mary Ann; Acton, Tara; Robbins, Steve

    2013-01-01

    This study examines the effects of math readiness and student course behavior (e.g., attendance, participation, homework completion) on knowledge gain and course success using two samples of students enrolled in foundational skills (noncredit-bearing) mathematics courses. As hypothesized, entering student mathematics readiness and course behavior…

  9. Social Skills: Laying the Foundation for Success

    ERIC Educational Resources Information Center

    Lynch, Sharon A.; Simpson, Cynthia G.

    2010-01-01

    Well-informed teachers of young children recognize the importance of children's social development. The development of social skills lays a critical foundation for later academic achievement as well as work-related skills. Social development is such a key issue with young children that a number of methods to address social skills have been…

  10. Foundation: Transforming data bases into knowledge bases

    NASA Technical Reports Server (NTRS)

    Purves, R. B.; Carnes, James R.; Cutts, Dannie E.

    1987-01-01

    One approach to transforming information stored in relational data bases into knowledge based representations and back again is described. This system, called Foundation, allows knowledge bases to take advantage of vast amounts of pre-existing data. A benefit of this approach is inspection, and even population, of data bases through an intelligent knowledge-based front-end.

  11. Pavlov and the foundation of behavior therapy.

    PubMed

    Plaud, Joseph J

    2003-11-01

    The foundation, achievements, and proliferation of behavior therapy have largely been fueled by the movement's foundation in behavioral principles and theories. Although behavioral accounts of the genesis and treatment of psychopathology differ in the extent to which they emphasize classical or operant conditioning, the mediation of cognitive factors, and the role of biological variables, Pavlov's discovery of conditioning principles was essential to the founding of behavior therapy in the 1950s, and continues to be central to modern behavior therapy. Pavlov's reliance on a physiological model of the nervous system, sensible in the context of an early science of neurology, has had an implication for behavior therapists interested in the study of personality types. However, Pavlov's major legacy to behavior therapy was his discovery of "experimental neuroses," shown by his students Eroféeva and Shenger-Krestovnikova, to be produced and eliminated through the principles of conditioning and counter-conditioning. This discovery laid the foundation for the first empirically-validated behavior therapy procedure, systematic desensitization, pioneered by Wolpe. The Pavlovian origins of behavior therapy are analyzed in this paper, and the relevance of conditioning principles to modern behavior therapy is demonstrated. It is shown that Pavlovian conditioning represents far more than a systematic basic learning paradigm. It is also an essential theoretical foundation for the theory and practice of behavior therapy. PMID:14628701

  12. Plain English: The Language of Foundations.

    ERIC Educational Resources Information Center

    McGuire, Betty E.

    1981-01-01

    Since hundreds of requests for grants appear at the offices of American foundations, a proposal that wastes an opportunity by making a poor case cannot be tolerated. Suggestions are given for beginning the grant-writing, drafting the proposal, and avoiding certain problem approaches. (Author/MSE)

  13. The Emotional Foundations of Social Understanding

    ERIC Educational Resources Information Center

    Warren, Heather K.; Denham, Susanne A.; Bassett, Hideko H.

    2008-01-01

    The infant and toddler years are a watershed of development in the emotional domain. These skills lay the foundation for positive social interactions, and ultimately, academic and life success. This article describes the development of three skills that are central in creating successful relationships: expressing emotion, understanding emotion,…

  14. Theoretical Foundations for Website Design Courses.

    ERIC Educational Resources Information Center

    Walker, Kristin

    2002-01-01

    Considers how theoretical foundations in website design courses can facilitate students learning the genres of Internet communication. Proposes ways that theories can be integrated into website design courses. Focuses on two students' website portfolios and ways they utilize genre theory and activity theory discussed in class to produce websites…

  15. Foundation for the Future: Turning Points.

    ERIC Educational Resources Information Center

    National Science Foundation, Arlington, VA. Directorate for Education and Human Resources.

    This booklet, the third publication in the Foundation for the Future series, illustrates how involvement in the Directorate for Education and Human Resources' (EHR's) projects has been a watershed for many people. The personal profiles contained within describe how EHR programs are: changing people's lives, opening people's minds to new…

  16. The Philosophical Foundations of Lifelong Learning.

    ERIC Educational Resources Information Center

    Michopoulos, Aristotle

    The current lifelong learning movement, the new force toward global education, owes much to the League of Nations and the United Nations that sponsored an expanded multiracial "polis." Its philosophical foundations go back, however, to ancient China, India, and especially Greece, where philosophers and scientists got their creative stimulus from…

  17. Philosophical Foundations of Adult Education. Second Edition.

    ERIC Educational Resources Information Center

    Elias, John L.; Merriam, Sharan B.

    This book examines the philosophical foundations of adult education (AE). The following topics are discussed: philosophy of AE (philosophy and action in theory and practice and philosophy for adult educators); liberal AE (historical development, liberal education and the educated person, broad scope, process, liberal education of adults, Great…

  18. Fundraising in Community College Foundations. ERIC Digest.

    ERIC Educational Resources Information Center

    Schuyler, Gwyer

    In response to declining local and state appropriations for public education, community colleges have taken steps to formalize fundraising efforts by creating institutional foundations as recipients of tax-deductible contributions. Large-scale external fundraising at community colleges began as a result of the 1965 Higher Education Act and the…

  19. National Science Foundation Annual Report 1976.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC.

    This document provides highlights of research efforts supported by the National Science Foundation (NSF) in the areas of mathematics, physical sciences, and engineering; astronomical, atmospheric, earth, and ocean sciences; science education; research applied to national needs; and scientific, technological, and international affairs for fiscal…

  20. National Science Foundation Annual Report 1979.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC.

    Presented are highlights of research efforts supported by the National Science Foundation (NSF) in the areas of mathematical and physical sciences; astronomical, atmospheric, earth, and ocean sciences; biological, behavioral, and social sciences; science education; engineering and applied science; and scientific, technological, and international…

  1. Theoretical Foundations of Rorschach by Piotrowski.

    ERIC Educational Resources Information Center

    Daly, William C.

    2005-01-01

    The writer has tried to lift the veil of mystery from the Rorschach Cards by uncovering in simple form the ten basic principles of Zygmunt Protrowski which can be considered the foundation stones of Rorschach; they are composed of psycho-justifications as well as meaningful administrative procedures allowing the reader broader understanding of…

  2. Bernard van Leer Foundation Newsletter, 1996.

    ERIC Educational Resources Information Center

    Bernard van Leer Foundation, Newsletter, 1996

    1996-01-01

    This document consists of the four issues of the Bernard van Leer Foundation's "Newsletter" published during 1996. The newsletter covers topics related to, or about efforts to foster, the education and welfare of children around the world, and includes descriptions of programs around the world, lists of resources and publications, and early…

  3. Research and the Bernard van Leer Foundation.

    ERIC Educational Resources Information Center

    Wall, W. D.

    1978-01-01

    Outlines Bernard van Leer Foundation sponsorship of action programs and research studies of child development in 25 countries. The problems and possibilities of such work are discussed from the viewpoint of evaluation and the contribution which can be made to the behavioral sciences--notably to comparative child development. (Author/RH)

  4. The Joyce Foundation 2011 Annual Report

    ERIC Educational Resources Information Center

    O'Connell, Mary

    2012-01-01

    In a period such as this, marked by extreme political partisanship and apparent gridlock at the federal level, it would be tempting to throw up one's hands in frustration. But this is just the time that a foundation like Joyce can add the most value--because the Joyce team members are non-partisan, not subject to the pressures of political and…

  5. Excavationless Exterior Foundation Insulation Field Study

    SciTech Connect

    Schirber, T.; Mosiman, G.; Ojczyk, C.

    2014-09-01

    Building science research supports installing exterior (soil side) foundation insulation as the optimal method to enhance the hygrothermal performance of new homes. With exterior foundation insulation, water management strategies are maximized while insulating the basement space and ensuring a more even temperature at the foundation wall. However, such an approach can be very costly and disruptive when applied to an existing home, requiring deep excavation around the entire house. The NorthernSTAR Building America Partnership team implemented an innovative, minimally invasive foundation insulation upgrade technique on an existing home. The approach consisted of using hydrovac excavation technology combined with liquid insulating foam. The team was able to excavate a continuous 4 inches wide by 4 feet to 5 feet deep trench around the entire house, 128 linear feet, except for one small part under the stoop that was obstructed with concrete debris. The combination pressure washer and vacuum extraction technology also enabled the elimination of large trenches and soil stockpiles normally produced by backhoe excavation. The resulting trench was filled with liquid insulating foam, which also served as a water-control layer of the assembly. The insulation was brought above grade using a liquid foam/rigid foam hybrid system and terminated at the top of the rim joist. Cost savings over the traditional excavation process ranged from 23% to 50%. The excavationless process could result in even greater savings since replacement of building structures, exterior features, utility meters, and landscaping would be minimal or non-existent in an excavationless process.

  6. Aboriginal Healing Foundation Annual Report, 2001.

    ERIC Educational Resources Information Center

    Aboriginal Healing Foundation, Ottawa (Ontario).

    The Aboriginal Healing Foundation (AHF) is a nonprofit organization established in 1998 with funding from the Canadian Government. Its mission is to support Aboriginal people in building sustainable healing processes that address the legacy of physical and sexual abuse in the residential school system, including intergenerational impacts. AHF…

  7. Foundations for Policy in Guidance and Counseling.

    ERIC Educational Resources Information Center

    Herr, Edwin L., Ed.; Pinson, Nancy M., Ed.

    This book provides educators, counselors, policy makers, and community members with information about the state of the art of federal and state policy in guidance and counseling. The two chapters in part 1, Overview, are: "Foundations for Policy in Guidance and Counseling: An Introduction", by Edwin L. Herr and Nancy M. Pinson; and "A Counselor…

  8. FELS FOUNDATION PROJECT FOR DEVELOPING YOUTH POTENTIAL.

    ERIC Educational Resources Information Center

    BAIR, ROBERT A.; AND OTHERS

    THE OPERATION OF THE FELS FOUNDATION PROJECT FOR DEVELOPING YOUTH POTENTIAL IN HANFORD, CALIFORNIA, IS DESCRIBED. OF GENERAL CONCERN WAS THE PREPARATION OF CULTURALLY DEPRIVED CHILDREN FOR SCHOOL EXPERIENCES AND FOR FUTURE EMPLOYMENT. A MAJOR GOAL WAS TO IMPROVE THE SELF-IMAGE OF THE CHILDREN AND TO ASSIST THE PARENTS AND CHILDREN IN PROVIDING…

  9. Corner Office Interview: Gates Foundation's Deborah Jacobs

    ERIC Educational Resources Information Center

    Miller, Rebecca

    2010-01-01

    U.S. libraries gave the world a top talent when Deborah Jacobs left her transformational role as City Librarian of Seattle in 2008 to head the Bill & Melinda Gates Foundation's Global Libraries program, the international sibling to the U.S. Libraries program. The initiative fosters national-scale projects with grantees in transitioning countries…

  10. Foundations for Effective School Library Media Programs.

    ERIC Educational Resources Information Center

    Haycock, Ken, Ed.

    This collection of 38 articles, reprinted from "Emergency Librarian," addresses critical elements of school library media program development and implementation, organized by seven areas: foundations; the school context; role clarification; information literacy; collaborative program planning and teaching; program development; and accountability.…

  11. Theoretical Foundations of Learning Environments. Second Edition

    ERIC Educational Resources Information Center

    Jonassen, David, Ed.; Land, Susan, Ed.

    2012-01-01

    "Theoretical Foundations of Learning Environments" provides students, faculty, and instructional designers with a clear, concise introduction to the major pedagogical and psychological theories and their implications for the design of new learning environments for schools, universities, or corporations. Leading experts describe the most important…

  12. The National Science Foundation: A Brief History.

    ERIC Educational Resources Information Center

    National Science Foundation, Washington, DC.

    On May 10, 1950, President Truman signed the bill creating the National Science Foundation (NSF). The act provided for a National Science Board to be created and the law directed the agency to encourage and develop a national policy for the promotion of basic research and education in the mathematical, physical, medical, biological, engineering,…

  13. Online Assessment and Measurement: Foundations and Challenges

    ERIC Educational Resources Information Center

    Hricko, Mary; Howell, Scott

    2006-01-01

    Online learning is one of the most important topics in distance learning, but practitioners and researchers have experienced difficulty in defining the process. "Online Assessment and Measurement: Foundations and Challenges" approaches the topic by finding a common ground to properly analyze online assessment and measurement. "Online Assessment…

  14. Foundational Academic Development: Building Collegiality across Divides?

    ERIC Educational Resources Information Center

    Clarke, Catherine; Reid, Jacqueline

    2013-01-01

    There is limited research into the effectiveness of non-accredited foundational courses for new academic staff. An ongoing issue is that of attention and anxiety overload in the critical first period of employment when the challenges of establishing oneself in a new collegial environment are most acute. Approaches to addressing this issue may be…

  15. Sound Foundations. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2006

    2006-01-01

    "Sound Foundations," a literacy curriculum designed to teach phonological awareness to preliterate children, focuses exclusively on phoneme identity (that is, different words can start and end with the same sound). It works from the principle that phonemic awareness is necessary but not sufficient to reading, which depends on the alphabetic…

  16. Deriving a Pedagogy of Educational Foundations

    ERIC Educational Resources Information Center

    Fenstermacher, Gary D.

    2007-01-01

    This sixth and last paper in the series describes four elements believed to be crucial to a high quality pedagogy for educational foundations. These four elements are derived from a close reading of the previous papers. The work of Osguthorpe, Sanger, Haniford, and Mucher, four of the authors in this series, is cited as both a source for these…

  17. Cultural Foundations of Education. Second Edition.

    ERIC Educational Resources Information Center

    Pai, Young; Adler, Susan A.

    This book is designed to provide educators and prospective educators with knowledge essential to making decisions about teaching and learning. The book is intended as a foundation for thinking about curriculum and pedagogy. Case studies involving African American, Asian American, Hispanic American, Native American, and white American groups are…

  18. The Promises of Moral Foundations Theory

    ERIC Educational Resources Information Center

    Musschenga, Bert

    2013-01-01

    In this article I examine whether Moral Foundations Theory can fulfil the promises that Haidt claims for the theory: that it will help in developing new approaches to moral education and to the moral conflicts that divide our diverse society. I argue that, first, the model that Haidt suggests for understanding the plurality of moralities--a shared…

  19. Foundation literacy acquisition in European orthographies.

    PubMed

    Seymour, Philip H K; Aro, Mikko; Erskine, Jane M

    2003-05-01

    Several previous studies have suggested that basic decoding skills may develop less effectively in English than in some other European orthographies. The origins of this effect in the early (foundation) phase of reading acquisition are investigated through assessments of letter knowledge, familiar word reading, and simple nonword reading in English and 12 other orthographies. The results confirm that children from a majority of European countries become accurate and fluent in foundation level reading before the end of the first school year. There are some exceptions, notably in French, Portuguese, Danish, and, particularly, in English. The effects appear not to be attributable to differences in age of starting or letter knowledge. It is argued that fundamental linguistic differences in syllabic complexity and orthographic depth are responsible. Syllabic complexity selectively affects decoding, whereas orthographic depth affects both word reading and nonword reading. The rate of development in English is more than twice as slow as in the shallow orthographies. It is hypothesized that the deeper orthographies induce the implementation of a dual (logographic + alphabetic) foundation which takes more than twice as long to establish as the single foundation required for the learning of a shallow orthography.

  20. Western European Art Foundations and Publishing

    ERIC Educational Resources Information Center

    King, Lindsay M.; Clement, Russell T.

    2011-01-01

    Western European art foundations create invaluable opportunities for research and exhibition by artists, curators, and scholars. These activities are often documented and disseminated via high-quality publications. This article highlights an important but under-recognized collecting resource for academic and museum libraries by profiling several…

  1. Excavations and Foundations in Soft Soils

    NASA Astrophysics Data System (ADS)

    Kempfert, Hans-Georg; Gebreselassie, Berhane

    The book reviews the experiences with, as well as recent developments and research results on excavations and foundations in and on soft soil deposits. Geotechnical design and execution of civil engineering structures on very soft soils are usually associated with substantial difficulties.

  2. SUSTAINABLE CONCRETE FOR WIND TURBINE FOUNDATIONS.

    SciTech Connect

    BERNDT,M.L.

    2004-06-01

    The use of wind power to generate electricity continues to grow, especially given commitments by various countries throughout the world to ensure that a significant percentage of energy comes from renewable sources. In order to meet such objectives, increasingly larger turbines with higher capacity are being developed. The engineering aspects of larger turbine development tend to focus on design and materials for blades and towers. However, foundations are also a critical component of large wind turbines and represent a significant cost of wind energy projects. Ongoing wind research at BNL is examining two areas: (a) structural response analysis of wind turbine-tower-foundation systems and (b) materials engineering of foundations. This work is investigating the dynamic interactions in wind turbine systems, which in turn assists the wind industry in achieving improved reliability and more cost efficient foundation designs. The results reported herein cover initial studies of concrete mix designs for large wind turbine foundations and how these may be tailored to reduce cost and incorporate sustainability and life cycle concepts. The approach taken was to investigate material substitutions so that the environmental, energy and CO{sub 2}-impact of concrete could be reduced. The use of high volumes of ''waste'' materials in concrete was examined. These materials included fly ash, blast furnace slag and recycled concrete aggregate. In addition, the use of steel fiber reinforcement as a means to improve mechanical properties and potentially reduce the amount of bar reinforcement in concrete foundations was studied. Four basic mixes were considered. These were: (1) conventional mix with no material substitutions, (2) 50% replacement of cement with fly ash, (3) 50% replacement of cement with blast furnace slag and (4) 25% replacement of cement with fly ash and 25% replacement with blast furnace slag. Variations on these mixes included the addition of 1% by volume steel

  3. Suppression of experimental autoimmune myasthenia gravis in IL-10 gene-disrupted mice is associated with reduced B cells and serum cytotoxicity on mouse cell line expressing AChR.

    PubMed

    Poussin, M A; Goluszko, E; Hughes, T K; Duchicella, S I; Christadoss, P

    2000-11-01

    To analyze the role of interleukin-10 (IL-10) in experimental autoimmune myasthenia gravis (EAMG) pathogenesis, we induced clinical EAMG in C57BL/6 and IL-10 gene-knockout (KO) mice. IL-10 KO mice had a lower incidence and severity of EAMG, with less muscle acetylcholine receptor (AChR) loss. AChR-immunized IL-10 KO mice showed a significantly higher AChR-specific proliferative response, altered cytokine response, lower number of class II-positive cells and B-cells, but a greater CD5(+)CD19(+) population than C57BL/6 mice. The lower clinical incidence in IL-10 KO could be explained not by a reduction of the quantity, but by a possible difference in the pathogenicity of anti-AChR antibodies.

  4. Rodent habenulo-interpeduncular pathway expresses a large variety of uncommon nAChR subtypes, but only the α3β4* and α3β3β4* subtypes mediate acetylcholine release

    PubMed Central

    Grady, Sharon R.; Moretti, Milena; Zoli, Michele; Marks, Michael J.; Zanardi, Alessio; Pucci, Luca; Clementi, Francesco; Gotti, Cecilia

    2009-01-01

    Recent studies suggest that the neuronal nicotinic receptors (nAChRs) present in the habenulo-interpeduncular (Hb-IPn) system can modulate the reinforcing effect of addictive drugs and the anxiolytic effect of nicotine. Hb and IPn neurons express mRNAs for most nAChR subunits thus making it difficult to establish the subunit composition of functional receptors. We used immunoprecipitation and immunopurification studies performed in rat, and wildtype (+/+) and β2 knockout (−/−) mice to establish that the Hb and IPn contain significant β2* and β4* populations of nAChR receptors (each of which is heterogeneous). The β4* nAChR are more highly expressed in the IPn. We also identified novel native subtypes (α2β2*, α4β3β2*α3β3β4*, α6β3β4*). Our studies on IPn synaptosomes obtained from +/+ and α2, α4, α5, α6, α7, β2, β3 and β4−/− mice, show that only the α3β4 and α3β3β4 subtypes facilitate acetylcholine (ACh) release. Ligand binding, immunoprecipitation and Western blotting studies in β3−/− mice showed that in the IPn of these mice there is a concomitant reduction of ACh release and α3β4* receptors, while the receptor number remains the same in the Hb. We suggest that in habenular cholinergic neurons the β3 subunit may be important for transporting the α3β4* subtype from the medial habenula (MHb) to the IPn. Overall, these studies highlight the presence of a wealth of uncommon nAChR subtypes in the Hb-IPn system and identify α3β4 and α3β3β4, transported from the Hb and highly enriched in the IPn, as the subtypes modulating ACh release in the IPn. PMID:19228980

  5. Acetylcholine Receptor (AChR) Clustering Is Regulated Both by Glycogen Synthase Kinase 3β (GSK3β)-dependent Phosphorylation and the Level of CLIP-associated Protein 2 (CLASP2) Mediating the Capture of Microtubule Plus-ends*

    PubMed Central

    Basu, Sreya; Sladecek, Stefan; Pemble, Hayley; Wittmann, Torsten; Slotman, Johan A.; van Cappellen, Wiggert; Brenner, Hans-Rudolf; Galjart, Niels

    2014-01-01

    The postsynaptic apparatus of the neuromuscular junction (NMJ) traps and anchors acetylcholine receptors (AChRs) at high density at the synapse. We have previously shown that microtubule (MT) capture by CLASP2, a MT plus-end-tracking protein (+TIP), increases the size and receptor density of AChR clusters at the NMJ through the delivery of AChRs and that this is regulated by a pathway involving neuronal agrin and several postsynaptic kinases, including GSK3. Phosphorylation by GSK3 has been shown to cause CLASP2 dissociation from MT ends, and nine potential phosphorylation sites for GSK3 have been mapped on CLASP2. How CLASP2 phosphorylation regulates MT capture at the NMJ and how this controls the size of AChR clusters are not yet understood. To examine this, we used myotubes cultured on agrin patches that induce AChR clustering in a two-dimensional manner. We show that expression of a CLASP2 mutant, in which the nine GSK3 target serines are mutated to alanine (CLASP2–9XS/9XA) and are resistant to GSK3β-dependent phosphorylation, promotes MT capture at clusters and increases AChR cluster size, compared with myotubes that express similar levels of wild type CLASP2 or that are noninfected. Conversely, myotubes expressing a phosphomimetic form of CLASP2 (CLASP2–8XS/D) show enrichment of immobile mutant CLASP2 in clusters, but MT capture and AChR cluster size are reduced. Taken together, our data suggest that both GSK3β-dependent phosphorylation and the level of CLASP2 play a role in the maintenance of AChR cluster size through the regulated capture and release of MT plus-ends. PMID:25231989

  6. Can Innate, modular "foundations" explain morality? Challenges for Haidt's Moral Foundations Theory.

    PubMed

    Suhler, Christopher L; Churchland, Patricia

    2011-09-01

    Jonathan Haidt's Moral Foundations Theory is an influential scientific account of morality incorporating psychological, developmental, and evolutionary perspectives. The theory proposes that morality is built upon five innate "foundations," each of which is believed to have been selected for during human evolution and, subsequently, tuned-up by learning during development. We argue here that although some general elements of Haidt's theory are plausible, many other important aspects of his account are seriously flawed. First, innateness and modularity figure centrally in Haidt's account, but terminological and conceptual problems foster confusion and ambiguities. Second, both the theory's proposed number of moral foundations and its taxonomy of the moral domain appear contrived, ignoring equally good candidate foundations and the possibility of substantial intergroup differences in the foundations' contents. Third, the mechanisms (viz., modules) and categorical distinctions (viz., between foundations) proposed by the theory are not consilient with discoveries in contemporary neuroscience concerning the organization, functioning, and development of the brain. In light of these difficulties, we suggest that Haidt's theory is inadequate as a scientific account of morality. Nevertheless, the theory's weaknesses are instructive, and hence, criticism may be useful to psychologists, neuroscientists, and philosophers attempting to advance theories of morality, as well as to researchers wishing to invoke concepts such as innateness and modularity more generally.

  7. Technique in Cleft Rhinoplasty: The Foundation Graft.

    PubMed

    Gassner, Holger G; Schwan, Franziska; Haubner, Frank; Suárez, Gustavo A; Vielsmeier, Veronika

    2016-04-01

    Secondary cleft rhinoplasty represents a particular surgical challenge. The authors have identified the deficit in skeletal projection of the cleft-sided piriform rim as an important contributor to the pathology. A graft is described to augment the piriform crest on the cleft side. This foundation graft is suture fixated to the piriform crest after complete release of all soft tissue attachments to the alar base. The foundation graft is articulated with a long alar strut graft, which allows for powerful projection of the cleft-sided nasal tip. An advancement flap of vestibular skin is described to correct the vestibular stenosis. A transplant of diced cartilage in fascia is added to augment maxillary soft tissue volume. Subjective and objective measures of form and function are presented in a retrospective series of five cases, illustrating the efficacy of the techniques described. PMID:27097143

  8. Excavationless Exterior Foundation Insulation Exploratory Study

    SciTech Connect

    Mosimann, Garrett; Wagner, Rachel; Schirber, Tom

    2013-02-01

    The key objective of this exploratory study was to investigate the feasibility of the development or adoption of technologies that would enable a large percentage of existing homes in cold climates to apply a combination 'excavationless' soil removal process with appropriate insulation and water management on the exterior of existing foundations at a low cost. Our approach was to explore existing excavation and material technologies and systems to discover whether potential successful combinations existed.

  9. Foundation Trusts: economics in the 'postmodern hospital'.

    PubMed

    Newbold, David

    2005-09-01

    Foundation Trust Hospitals are community-controlled health care providers which have increased autonomy about how they produce outcomes for the British National Health Service. Although there is a literature on hospital economics it is unclear how these innovative providers will behave, if they have to compete for scarce resources with other hospitals. This paper reviews some of the earlier theories, such as the neoclassical theory of the firm, and discusses their relevance along with 'newer' economic theories such as the transaction costs and evolutionary theory of the firm, plus organizational and human resources theory, to the performance of Foundation Trusts. Much contemporary health care provision is shaped along modernist lines, using scientific endeavour to maximize the impact on health outcomes and technical and social efficiency. However, there is an increasingly postmodern standpoint--critical of modernity--being taken by both patients and hospital staff, to deconstruct processes in the organizations that serve them. Foundation Trusts are postmodern hospitals insomuch as they (to attract scarce resources in a competitive environment), need to marshal the diverse theories of the firm together in order to provide a mass-customized, quality experience, transparently and at least cost--whilst maintaining a stable organizational culture for staff.

  10. Preliminary Geological Map of the Ac-H-8 Nawish Quadrangle of Ceres: An Integrated Mapping Study Using Dawn Spacecraft Data

    NASA Astrophysics Data System (ADS)

    Frigeri, Alessandro; De Sanctis, Maria Cristina; Carrozzo, Giacomo; Ammannito, Eleonora; Williams, David; Mest, Scott; Buczkowski, Debra; Preusker, Frank; Jaumann, Ralf; Roatsch, Thomas; Scully, Jennifer; Raymond, Carol; Russell, Christopher

    2016-04-01

    Herein we present the geologic mapping of the Ac-H-8 Nawish Quadrangle of dwarf planet Ceres, produced on the basis of the Dawn spacecraft data. The Ac-H-08 Nawish quadrangle is located between -22°S and 22°N and between 144°E and 216°E. At the north-east border, a polygonal, 75km-wide crater named Nawish gives the name to the whole quadrangle. An unamed, partially degraded, 100km-diameter crater is evident in the lower central sector of the quadrangle. Bright materials have been mapped and are associated with craters. For example, bright materials occur in the central peak region of Nawish crater and in the ejecta of an unnamed crater, which is located in the nearby quadrangle Ac-H-09. The topography of the area obtained from stereo-processing of imagery shows an highland in the middle of the quadrangle. Topography is lower in the northern and southern borders, with a altitude span of about 9500 meters. At the time of this writing geologic mapping was based on Framing Camera (FC) mosaics from the High Altitude Mapping Orbit (HAMO, 140 m/px) and Survey (415 m/px) orbits, including grayscale and color images and digital terrain models derived from stereo images. The first sessions of Low Altitude Mapping Orbit (LAMO, 35 m/px) images have been received as we are writing this abstract in the first half of January 2016. LAMO images represent the maximum spatial resolution images available for Ceres from the Dawn mission. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA, and from the German and Italian Space Agencies.

  11. Identification of the Chemical Bonding Prompting Adhesion of a-C:H Thin Films on Ferrous Alloy Intermediated by a SiCx:H Buffer Layer.

    PubMed

    Cemin, F; Bim, L T; Leidens, L M; Morales, M; Baumvol, I J R; Alvarez, F; Figueroa, C A

    2015-07-29

    Amorphous carbon (a-C) and several related materials (DLCs) may have ultralow friction coefficients that can be used for saving-energy applications. However, poor chemical bonding of a-C/DLC films on metallic alloys is expected, due to the stability of carbon-carbon bonds. Silicon-based intermediate layers are employed to enhance the adherence of a-C:H films on ferrous alloys, although the role of such buffer layers is not yet fully understood in chemical terms. The chemical bonding of a-C:H thin films on ferrous alloy intermediated by a nanometric SiCx:H buffer layer was analyzed by X-ray photoelectron spectroscopy (XPS). The chemical profile was inspected by glow discharge optical emission spectroscopy (GDOES), and the chemical structure was evaluated by Raman and Fourier transform infrared spectroscopy techniques. The nature of adhesion is discussed by analyzing the chemical bonding at the interfaces of the a-C:H/SiCx:H/ferrous alloy sandwich structure. The adhesion phenomenon is ascribed to specifically chemical bonding character at the buffer layer. Whereas carbon-carbon (C-C) and carbon-silicon (C-Si) bonds are formed at the outermost interface, the innermost interface is constituted mainly by silicon-iron (Si-Fe) bonds. The oxygen presence degrades the adhesion up to totally delaminate the a-C:H thin films. The SiCx:H deposition temperature determines the type of chemical bonding and the amount of oxygen contained in the buffer layer.

  12. Preliminary Geological Map of the Ac-H-8 Nawish Quadrangle of Ceres: An Integrated Mapping Study Using Dawn Spacecraft Data

    NASA Astrophysics Data System (ADS)

    Frigeri, A.; De Sanctis, M. C.; Carrorro, F. G.; Ammannito, E.; Williams, D. A.; Mest, S. C.; Buczkowski, D.; Preusker, F.; Jaumann, R.; Roatsch, T.; Scully, J. E. C.; Raymond, C. A.; Russell, C. T.

    2015-12-01

    Herein we present the geologic mapping of the Ac-H-8 Nawish Quadrangle of dwarf planet Ceres, produced on the basis of the Dawn spacecraft data. The Ac-H-08 Nawish quadrangle is located between -22°S and 22°N and between 144°E and 216°E. At the north-east border, a polygonal, 75km-wide crater named Nawish gives the name to the whole quadrangle. An unamed, partially degraded, 100km-diameter crater is evident in the lower central sector of the quadrangle. Bright materials have been mapped and are associated with craters. For example, bright materials occur in the central peak region of Nawish crater and in the ejecta of an unnamed crater, which is located in the nearby quadrangle Ac-H-09. The topography of the area obtained from stereo-processing of imagery shows an highland in the middle of the quadrangle. Topography is lower in the northern and southern borders, with a altitude span of about 9500 meters. At the time of this writing geologic mapping was performed on Framing Camera (FC) mosaics from the Approach (1.3 km/px) and Survey (415 m/px) orbits, including grayscale and color images and digital terrain models derived from stereo images. In Fall 2015 images from the High Altitude Mapping Orbit (140 m/px) will be used to refine the mapping, followed by Low Altitude Mapping Orbit (35 m/px) images in January 2016. Support of the Dawn Instrument, Operations, and Science Teams is acknowledged. This work is supported by grants from NASA, and from the German and Italian Space Agencies.

  13. Molecular dynamical simulations on a-C:H film growth from atomic flux of C and H: Effect of H fraction

    NASA Astrophysics Data System (ADS)

    Quan, W. L.; Li, H. X.; Zhao, F.; Ji, L.; Du, W.; Zhou, H. D.; Chen, J. M.

    2010-04-01

    Molecular dynamical simulations are carried out to studying the hydrogenated amorphous carbon (a-C:H) film growth from C and H atoms. The effects of the H fraction in source atoms and incident energy on the film formation are investigated. Our simulations show that almost all the H atoms incorporating into the films bond to carbon and the amount of H 2 molecules is very slight. Increasing the H fraction in source atoms raises the sp 3-C fraction, leads to a linear increase of H concentration in film, but decreases the film growth rate. The influence of H fraction on the film growth mechanism is also discussed.

  14. The Role of Community College Trustees in Supporting the Foundation

    ERIC Educational Resources Information Center

    Nielsen, Norm; Newton, Wayne; Mitvalsky, Cheryle W.

    2003-01-01

    The role of the institutional trustees in supporting foundation efforts is explored. Four priorities are described: projecting a positive image for the college, overseeing and maintaining an institutional structure that supports the foundation, sustaining an engaged administration, and encouraging innovation.

  15. IET. Exhaust stack foundation under construction. Reinforced concrete footings for ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    IET. Exhaust stack foundation under construction. Reinforced concrete footings for duct at right of stack. Foundation is in octagonal shape. Date: October 29, 1954. INEEL negative no. 12711 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

  16. 14. FLOODED POWER HOUSE FOUNDATION EXCAVATION BEING PUMPED OUT. NOTE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. FLOODED POWER HOUSE FOUNDATION EXCAVATION BEING PUMPED OUT. NOTE KEYS IN FOREBAY ABUTMENT TO INTERLOCK WITH POWER HOUSE FOUNDATION, March 1918. - Dam No. 5 Hydroelectric Plant, On Potomac River, Hedgesville, Berkeley County, WV

  17. Sub-micro a-C:H patterning of silicon surfaces assisted by atmospheric-pressure plasma-enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Boileau, Alexis; Gries, Thomas; Noël, Cédric; Perito Cardoso, Rodrigo; Belmonte, Thierry

    2016-11-01

    Micro and nano-patterning of surfaces is an increasingly popular challenge in the field of the miniaturization of devices assembled via top-down approaches. This study demonstrates the possibility of depositing sub-micrometric localized coatings—spots, lines or even more complex shapes—made of amorphous hydrogenated carbon (a-C:H) thanks to a moving XY stage. Deposition was performed on silicon substrates using chemical vapor deposition assisted by an argon atmospheric-pressure plasma jet. Acetylene was injected into the post-discharge region as a precursor by means of a glass capillary with a sub-micrometric diameter. A parametric study was carried out to study the influence of the geometric configurations (capillary diameter and capillary-plasma distance) on the deposited coating. Thus, the patterns formed were investigated by scanning electron microscopy and atomic force microscopy. Furthermore, the chemical composition of large coated areas was investigated by Fourier transform infrared spectroscopy according to the chosen atmospheric environment. The observed chemical bonds show that reactions of the gaseous precursor in the discharge region and both chemical and morphological stability of the patterns after treatment are strongly dependent on the surrounding gas. Various sub-micrometric a-C:H shapes were successfully deposited under controlled atmospheric conditions using argon as inerting gas. Overall, this new process of micro-scale additive manufacturing by atmospheric plasma offers unusually high-resolution at low cost.

  18. Acetylsalicylic acid and ascorbic acid combination improves cognition; via antioxidant effect or increased expression of NMDARs and nAChRs?

    PubMed

    Kara, Yusuf; Doguc, Duygu Kumbul; Kulac, Esin; Gultekin, Fatih

    2014-05-01

    Chronic inflammation occurs systematically in the central nervous system during ageing, it has been shown that neuroinflammation plays an important role in the pathogenesis of many neurodegenerative disorders. Aspirin, a nonselective COX inhibitor, as well as ascorbic acid, has been purported to protect cerebral tissue. We investigated the effects of subchronic aspirin and ascorbic acid usage on spatial learning, oxidative stress and expressions of NR2A, NR2B, nAChRα7, α4 and β2. Forty male rats (16-18 months) were divided into 4 groups, namely, control, aspirin-treated, ascorbic acid-treated, aspirin+ascorbic acid-treated groups. Following 10-weeks administration period, rats were trained and tested in the Morris water maze. 8-Hydroxy-2-deoxyguanosine and malondialdehyde were evaluated by ELISA and HPLC, respectively. Receptor expressions were assessed by western blotting of hippocampi. Spatial learning performance improved partially in the aspirin group, but significant improvement was seen in the aspirin+ascorbic acid group (p < 0.05). While 8-hydroxy-2-deoxyguanosine and malondialdehyde levels were significantly decreased, NR2B and nAChRα7 expressions were significantly increased in the aspirin+ascorbic acid group as compared to the control group (p < 0.05). Subchronic treatment with aspirin+ascorbic acid in aged rats was shown to enhance cognitive performance and increase the expressions of several receptors related to learning and memory process.

  19. The influence of DC biasing on the uniformity of a-C:H films for three-dimensional substrates by using a plasma-based ion implantation technique

    NASA Astrophysics Data System (ADS)

    Watanabe, Toshiya; Yamamoto, Kazuhiro; Tsuda, Osamu; Tanaka, Akihiro; Koga, Yoshinori; Takai, Osamu

    2003-05-01

    Amorphous hydrogenated carbon (a-C:H) films were synthesized by the use of a PBII technique using an electron cyclotron resonance plasma source with a mirror field, and the influence of the biasing conditions on the properties and the uniformity of the three-dimensional surfaces of a-C:H films was investigated. For convex faces, the film thickness was almost constant, independent of the deposition conditions, because a uniform plasma surrounded the substrates. For concave faces, the thickness of the films that formed without biasing and with only the application of a pulse bias decreased when the microwave-incident angle was decreased. On the other hand, when a DC bias was applied to the substrate in addition to a pulse bias, the uniformity of the thickness was much improved with a distribution within ±10%. The improvement in the uniformity was assumed to be the result of the continuous supply of ions in the plasma to the surfaces by the DC biasing.

  20. Electrical And OES Diagnostics Of A Magnetized RF Discharge In CH{sub 4} Created By A Multihole Cathode Used For a-C:H Deposition

    SciTech Connect

    Djerourou, S.; Henda, K.; Ouchabane, M.

    2008-09-23

    The present work is carried out in the context of the electrical and spectroscopic study of a reactor used for a-C:H deposition. We have studied the influence of the operation system parameters (incident power, pressure) on the self-bias voltage and on the saturation ion current density. The optical emission spectroscopy (OES) is used for the diagnostic by actinometry to determine the relative concentration of species (CH, H) present in the discharge. These measurements have been made over a wide range of incident power inputs of 50-300 W and pressures of 20-100 mTorr. For electrical diagnostic, the results obtained showed that the energy and ion flow bombarding the substrate presented a maximum values at high incident power and decreased with pressure. For spectroscopic diagnostic, the relative concentration of hydrogen and the kinetic of methylidyne radical versus the operation system parameters are studied. The first correlation between electrical and spectroscopic parameters and a-C:H deposition was found, polymer-like thin films with high deposition rates can be obtained at low pressure and with grounded substrate holder.

  1. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats.

    PubMed

    Sun, Fen; Jin, Kunlin; Uteshev, Victor V

    2013-01-01

    In the absence of clinically-efficacious therapies for ischemic stroke there is a critical need for development of new therapeutic concepts and approaches for prevention of brain injury secondary to cerebral ischemia. This study tests the hypothesis that administration of PNU-120596, a type-II positive allosteric modulator (PAM-II) of α7 nicotinic acetylcholine receptors (nAChRs), as long as 6 hours after the onset of focal cerebral ischemia significantly reduces brain injury and neurological deficits in an animal model of ischemic stroke. Focal cerebral ischemia was induced by a transient (90 min) middle cerebral artery occlusion (MCAO). Animals were then subdivided into two groups and injected intravenously (i.v.) 6 hours post-MCAO with either 1 mg/kg PNU-120596 (treated group) or vehicle only (untreated group). Measurements of cerebral infarct volumes and neurological behavioral tests were performed 24 hrs post-MCAO. PNU-120596 significantly reduced cerebral infarct volume and improved neurological function as evidenced by the results of Bederson, rolling cylinder and ladder rung walking tests. These results forecast a high therapeutic potential for PAMs-II as effective recruiters and activators of endogenous α7 nAChR-dependent cholinergic pathways to reduce brain injury and improve neurological function after cerebral ischemic stroke. PMID:23951360

  2. Boot Camp for Education CEOs: The Broad Foundation Superintendents Academy

    ERIC Educational Resources Information Center

    Jehlen, Alain

    2012-01-01

    The Broad Foundation Superintendents Academy is the most prominent and most controversial training institute for school chiefs. The Academy is the flagship program of the Eli and Edythe Broad Foundation, the smallest of a triumvirate of corporate foundations that are at the heart of the billionaire campaign to remake public education in the image…

  3. 26 CFR 1.507-3 - Special rules; transferee foundations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Special rules; transferee foundations. 1.507-3... TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.507-3 Special rules; transferee foundations. (a) General rule. (1) For purposes of part II, subchapter F, chapter 1 of the Code, in the...

  4. 26 CFR 1.507-3 - Special rules; transferee foundations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Special rules; transferee foundations. 1.507-3... TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.507-3 Special rules; transferee foundations. (a) General rule. (1) For purposes of part II, subchapter F, chapter 1 of the Code, in the...

  5. 26 CFR 1.507-3 - Special rules; transferee foundations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Special rules; transferee foundations. 1.507-3... TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.507-3 Special rules; transferee foundations. (a) General rule. (1) For purposes of part II, subchapter F, chapter 1 of the Code, in the...

  6. 26 CFR 1.507-3 - Special rules; transferee foundations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Special rules; transferee foundations. 1.507-3... TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.507-3 Special rules; transferee foundations. (a) General rule. (1) For purposes of part II, subchapter F, chapter 1 of the Code, in the...

  7. 45 CFR 650.2 - National Science Foundation patent policy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false National Science Foundation patent policy. 650.2 Section 650.2 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.2 National Science Foundation patent policy. As authorized by the National...

  8. 45 CFR 650.2 - National Science Foundation patent policy.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false National Science Foundation patent policy. 650.2 Section 650.2 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.2 National Science Foundation patent policy. As authorized by the National...

  9. 45 CFR 650.2 - National Science Foundation patent policy.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false National Science Foundation patent policy. 650.2... FOUNDATION PATENTS § 650.2 National Science Foundation patent policy. As authorized by the National Science... adopted the following statement of NSF patent policy. (a) In accordance with the Bayh-Dole Act and...

  10. 45 CFR 650.2 - National Science Foundation patent policy.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false National Science Foundation patent policy. 650.2... FOUNDATION PATENTS § 650.2 National Science Foundation patent policy. As authorized by the National Science... adopted the following statement of NSF patent policy. (a) In accordance with the Bayh-Dole Act and...

  11. 45 CFR 650.2 - National Science Foundation patent policy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false National Science Foundation patent policy. 650.2... FOUNDATION PATENTS § 650.2 National Science Foundation patent policy. As authorized by the National Science... adopted the following statement of NSF patent policy. (a) In accordance with the Bayh-Dole Act and...

  12. Foundational model of neuroanatomy: implications for the Human Brain Project.

    PubMed Central

    Martin, R. F.; Mejino, J. L.; Bowden, D. M.; Brinkley, J. F.; Rosse, C.

    2001-01-01

    In order to meet the need for a controlled terminology in neuroinformatics, we have integrated the extensive terminology of NeuroNames into the Foundational Model of anatomy. We illustrate the application of foundational principles for the establishment of an inheritance hierarchy, which accommodates anatomical attributes of neuroanatomical concepts and provides the foundation to which other information may be linked. PMID:11825226

  13. 26 CFR 1.642(c)-4 - Nonexempt private foundations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Nonexempt private foundations. 1.642(c)-4... private foundations. In the case of a trust which is, or is treated under section 4947(a)(1) as though it were, a private foundation (as defined in section 509(a) and the regulations thereunder) that is...

  14. 22 CFR 1002.5 - Records available at the Foundation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Records available at the Foundation. 1002.5 Section 1002.5 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.5 Records available at the Foundation. The General Counsel's Office will make available, to the extent not...

  15. 45 CFR 1100.7 - Foundation report of actions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Foundation report of actions. 1100.7 Section 1100.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS... AVAILABILITY OF INFORMATION § 1100.7 Foundation report of actions. On or before March 1 of each calendar...

  16. 22 CFR 1002.5 - Records available at the Foundation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Records available at the Foundation. 1002.5 Section 1002.5 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.5 Records available at the Foundation. The General Counsel's Office will make available, to the extent not...

  17. 22 CFR 1002.5 - Records available at the Foundation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Records available at the Foundation. 1002.5 Section 1002.5 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.5 Records available at the Foundation. The General Counsel's Office will make available, to the extent not...

  18. 22 CFR 1502.5 - Records available at the Foundation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Records available at the Foundation. 1502.5 Section 1502.5 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.5 Records available at the Foundation. The Administration and Finance Division will make available for...

  19. 22 CFR 1502.5 - Records available at the Foundation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 2 2012-04-01 2009-04-01 true Records available at the Foundation. 1502.5 Section 1502.5 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.5 Records available at the Foundation. The Administration and Finance Division will make available for...

  20. 26 CFR 1.642(c)-4 - Nonexempt private foundations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Nonexempt private foundations. 1.642(c)-4... private foundations. In the case of a trust which is, or is treated under section 4947(a)(1) as though it were, a private foundation (as defined in section 509(a) and the regulations thereunder) that is...

  1. 45 CFR 1100.7 - Foundation report of actions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Foundation report of actions. 1100.7 Section 1100.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS... AVAILABILITY OF INFORMATION § 1100.7 Foundation report of actions. On or before March 1 of each calendar...

  2. 26 CFR 1.642(c)-4 - Nonexempt private foundations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Nonexempt private foundations. 1.642(c)-4... private foundations. In the case of a trust which is, or is treated under section 4947(a)(1) as though it were, a private foundation (as defined in section 509(a) and the regulations thereunder) that is...

  3. 45 CFR 1100.7 - Foundation report of actions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 3 2014-10-01 2014-10-01 false Foundation report of actions. 1100.7 Section 1100.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS... AVAILABILITY OF INFORMATION § 1100.7 Foundation report of actions. On or before March 1 of each calendar...

  4. 26 CFR 1.642(c)-4 - Nonexempt private foundations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Nonexempt private foundations. 1.642(c)-4... foundations. In the case of a trust which is, or is treated under section 4947(a)(1) as though it were, a private foundation (as defined in section 509(a) and the regulations thereunder) that is not exempt...

  5. 45 CFR 1100.7 - Foundation report of actions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Foundation report of actions. 1100.7 Section 1100.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS... AVAILABILITY OF INFORMATION § 1100.7 Foundation report of actions. On or before March 1 of each calendar...

  6. 22 CFR 1002.5 - Records available at the Foundation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 2 2013-04-01 2009-04-01 true Records available at the Foundation. 1002.5 Section 1002.5 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.5 Records available at the Foundation. The General Counsel's Office will make available, to the extent not...

  7. 26 CFR 1.507-3 - Special rules; transferee foundations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Special rules; transferee foundations. 1.507-3... TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.507-3 Special rules; transferee foundations. (a) General rule. (1) For purposes of part II, subchapter F, chapter 1 of the Code, in the...

  8. 45 CFR 1100.7 - Foundation report of actions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 3 2013-10-01 2013-10-01 false Foundation report of actions. 1100.7 Section 1100.7 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL FOUNDATION ON THE ARTS... AVAILABILITY OF INFORMATION § 1100.7 Foundation report of actions. On or before March 1 of each calendar...

  9. 22 CFR 1502.5 - Records available at the Foundation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 2 2014-04-01 2014-04-01 false Records available at the Foundation. 1502.5 Section 1502.5 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.5 Records available at the Foundation. The Administration and Finance Division will make available for...

  10. 22 CFR 1502.5 - Records available at the Foundation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 2 2011-04-01 2009-04-01 true Records available at the Foundation. 1502.5 Section 1502.5 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.5 Records available at the Foundation. The Administration and Finance Division will make available for...

  11. 22 CFR 1002.5 - Records available at the Foundation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Records available at the Foundation. 1002.5 Section 1002.5 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.5 Records available at the Foundation. The General Counsel's Office will make available, to the extent not...

  12. 22 CFR 1502.5 - Records available at the Foundation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Records available at the Foundation. 1502.5 Section 1502.5 Foreign Relations AFRICAN DEVELOPMENT FOUNDATION AVAILABILITY OF RECORDS § 1502.5 Records available at the Foundation. The Administration and Finance Division will make available for...

  13. 26 CFR 1.642(c)-4 - Nonexempt private foundations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Nonexempt private foundations. 1.642(c)-4... private foundations. In the case of a trust which is, or is treated under section 4947(a)(1) as though it were, a private foundation (as defined in section 509(a) and the regulations thereunder) that is...

  14. "We Are Family": Maori Success in Foundation Programmes

    ERIC Educational Resources Information Center

    McMurchy-Pilkington, Colleen

    2013-01-01

    This paper considers the question: What constitutes an optimal learning environment for Maori learners in foundation programmes? Using Kaupapa Maori methodology, nearly 100 adult Maori (Indigenous) students in Aotearoa/New Zealand were interviewed from a range of tertiary providers of foundation programmes. State-funded foundation programmes that…

  15. 49 CFR 230.77 - Foundation brake gear.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Foundation brake gear. 230.77 Section 230.77... Tenders Brake and Signal Equipment § 230.77 Foundation brake gear. (a) Maintenance. Foundation brake gear shall be maintained in a safe and suitable condition for service. Levers, rods, brake beams,...

  16. 49 CFR 230.77 - Foundation brake gear.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Foundation brake gear. 230.77 Section 230.77... Tenders Brake and Signal Equipment § 230.77 Foundation brake gear. (a) Maintenance. Foundation brake gear shall be maintained in a safe and suitable condition for service. Levers, rods, brake beams,...

  17. 49 CFR 230.77 - Foundation brake gear.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Foundation brake gear. 230.77 Section 230.77... Tenders Brake and Signal Equipment § 230.77 Foundation brake gear. (a) Maintenance. Foundation brake gear shall be maintained in a safe and suitable condition for service. Levers, rods, brake beams,...

  18. 49 CFR 230.77 - Foundation brake gear.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Foundation brake gear. 230.77 Section 230.77... Tenders Brake and Signal Equipment § 230.77 Foundation brake gear. (a) Maintenance. Foundation brake gear shall be maintained in a safe and suitable condition for service. Levers, rods, brake beams,...

  19. 49 CFR 230.77 - Foundation brake gear.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Foundation brake gear. 230.77 Section 230.77... Tenders Brake and Signal Equipment § 230.77 Foundation brake gear. (a) Maintenance. Foundation brake gear shall be maintained in a safe and suitable condition for service. Levers, rods, brake beams,...

  20. Gentamicin blocks the ACh-induced BK current in guinea pig type II vestibular hair cells by competing with Ca²⁺ at the L-type calcium channel.

    PubMed

    Yu, Hong; Guo, Chang-Kai; Wang, Yi; Zhou, Tao; Kong, Wei-Jia

    2014-04-22

    Type II vestibular hair cells (VHCs II) contain big-conductance Ca²⁺-dependent K⁺ channels (BK) and L-type calcium channels. Our previous studies in guinea pig VHCs II indicated that acetylcholine (ACh) evoked the BK current by triggering the influx of Ca²⁺ ions through L-type Ca²⁺ channels, which was mediated by M2 muscarinic ACh receptor (mAChRs). Aminoglycoside antibiotics, such as gentamicin (GM), are known to have vestibulotoxicity, including damaging effects on the efferent nerve endings on VHCs II. This study used the whole-cell patch clamp technique to determine whether GM affects the vestibular efferent system at postsynaptic M2-mAChRs or the membrane ion channels. We found that GM could block the ACh-induced BK current and that inhibition was reversible, voltage-independent, and dose-dependent with an IC₅₀ value of 36.3 ± 7.8 µM. Increasing the ACh concentration had little influence on GM blocking effect, but increasing the extracellular Ca²⁺ concentration ([Ca²⁺]₀) could antagonize it. Moreover, 50 µM GM potently blocked Ca²⁺ currents activated by (-)-Bay-K8644, but did not block BK currents induced by NS1619. These observations indicate that GM most likely blocks the M2 mAChR-mediated response by competing with Ca²⁺ at the L-type calcium channel. These results provide insights into the vestibulotoxicity of aminoglycoside antibiotics on mammalian VHCs II.

  1. Measure Guideline. Hybrid Foundation Insulation Retrofits

    SciTech Connect

    Ueno, K.; Lstiburek, J.

    2012-05-01

    This measure guideline provides recommendations for designs and variations for retrofit hybrid assemblies in improving interior foundation insulation and water management of basements. Variations include closed cell spray foam (ccSPF) with membrane waterproofing or air gap membrane drainage layers, rigid board foam insulation at flat walls (cast concrete or CMU block), a “partial drainage” detail making use of the bulk water drainage that occurs through the field of a rubble stone wall, and non-drained spray foam assemblies (including slab insulation).

  2. Measure Guideline: Hybrid Foundation Insulation Retrofits

    SciTech Connect

    Ueno, K.; Lstiburek, J.

    2012-05-01

    This measure guideline provides recommendations for designs and variations for retrofit hybrid assemblies in improving interior foundation insulation and water management of basements. Variations include closed cell spray foam (ccSPF) with membrane waterproofing or air gap membrane drainage layers, rigid board foam insulation at flat walls (cast concrete or CMU block), a 'partial drainage' detail making use of the bulk water drainage that occurs through the field of a rubble stone wall, and non-drained spray foam assemblies (including slab insulation).

  3. Analysis of stone-column reinforced foundations

    NASA Astrophysics Data System (ADS)

    Lee, J. S.; Pande, G. N.

    1998-12-01

    A numerical model is proposed to analyse elastic as well as elastoplastic behaviour of stone-column reinforced foundations. The stone-columns are assumed to be dispersed within the in situ soil and a homogenization technique is invoked to establish equivalent material properties for in situ soil and stone-column composite. The difficulties encountered in carrying out elastoplastic analyses of composite materials are overcome by adopting a separate yield function for each of the constituent materials and a sub-iteration procedure within an implicit backward Euler stress integration scheme. In the proposed procedure, equilibrium as well as kinematic conditions implied in the homogenization procedure are satisfied for both elastic as well as elastoplastic stress states.The proposed model is implemented in an axi-symmetric finite element code and numerical prediction is made for the behaviour of model circular footings resting on stone-column reinforced foundations. This prediction indicates good agreement with experimental observation. Finally, a new scheme in which the length of stone-column is variable is proposed and its behaviour is examined through a numerical example.

  4. Teaching fellowships for UK foundation doctors.

    PubMed

    Qureshi, Shaun

    2015-01-01

    Teaching Fellowships for junior doctors in their second post-graduate (FY2) year should be considered by medical students and junior doctors in UK. FY2 Teaching Fellowships are available in many foundation schools as part of the UK Academic Foundation Programme. Although programme structures differ between schools, they are designed to allow junior trainees to take time out from clinical practice to develop their teaching skills and gain insights into medication education careers. The advantages of an FY2 teaching fellowship include valuable experience of teaching and formal feedback not available to other trainees; the opportunity to further develop your portfolio; further development of the trainee's own knowledge and skills; the stimulation of working with students. Potential drawbacks to be considered are reduced direct clinical contact; reduced salary; difficulty carrying out education research in the allocated time frame; occasional difficulties establishing the teacher-student relationship while the trainee is at a relatively junior level. Experience of medical education as an FY2 trainee provides a helpful stepping stone whether or not the trainee further pursues education as a career, because the teaching skills are transferable to any specialty, and the unique experience enhances the trainee's confidence as a role model for junior colleagues.

  5. Antennal cropping during colony foundation in termites

    PubMed Central

    Nalepa, Christine A.; Evans, Theodore A.; Lenz, Michael

    2011-01-01

    Abstract The literature on pairing and mating behavior in termites indicates that a number of distal antennal segments in dealates of both sexes are often removed during colony foundation, with terms such as amputation, mutilation and cannibalism typically employed to report the phenomenon. Here we propose the use of the phrase ‘antennal cropping’ to describe the behavior, and assess naturally occurring levels of its occurrence by comparing the number of antennal segments in museum specimens of alates and dealates in 16 species of Australian termites (four families), supplemented by analyzing published data on Coptotermes gestroi. Dealates had significantly fewer antennal segments than alates in 14 of the 16 termite species, with both exceptions belonging to the family Termitidae. Levels of antennal cropping were not significantly different between the sexes but did vary by family. Dealates in the Kalotermitidae removed the most segments (41.3%) and those in the Termitidae removed the fewest (8.9%). We discuss the biological significance of this phylogenetically widespread termite behavior, and suggest that controlled antennal cropping is not only a normal part of their behavioral repertoire but also a key influence that changes the conduct and physiology of the royal pair during the initial stages of colony foundation. PMID:22287897

  6. California settles lawsuit by AIDS Healthcare Foundation.

    PubMed

    1999-04-01

    The California Department of Health Services agreed to settle a lawsuit alleging it withheld funding from the AIDS Healthcare Foundation (AHF) in retaliation for AHF's advocacy on behalf of its clients. The public protest arose when the department attempted to cite one of the AHF hospices for not having a licensed nursing home administrator, which would have blocked Medi-Cal payments for patient care. For the type of facility being cited, having a nursing home administrator is not a requirement under State regulations. AHF charged the state with engaging in a pattern of discrimination, in violation of the Americans with Disabilities Act, the Federal Rehabilitation Act, and California's Unruh Civil Rights Act. A U.S. District judge granted summary judgment to the state on all claims except one transferring AHF's oversight responsibility to a county without AHF facilities. The transfer was viewed as having been aimed at AHF lobbying efforts and as an attempt to silence the foundation. The settlement returned AHF monitoring to Los Angeles County and dropped its claim that the two hospices had to hire a licensed nursing home administrator.

  7. Foundations for Measuring Volume Rendering Quality

    NASA Technical Reports Server (NTRS)

    Williams, Peter L.; Uselton, Samuel P.; Chancellor, Marisa K. (Technical Monitor)

    1997-01-01

    The goal of this paper is to provide a foundation for objectively comparing volume rendered images. The key elements of the foundation are: (1) a rigorous specification of all the parameters that need to be specified to define the conditions under which a volume rendered image is generated; (2) a methodology for difference classification, including a suite of functions or metrics to quantify and classify the difference between two volume rendered images that will support an analysis of the relative importance of particular differences. The results of this method can be used to study the changes caused by modifying particular parameter values, to compare and quantify changes between images of similar data sets rendered in the same way, and even to detect errors in the design, implementation or modification of a volume rendering system. If one has a benchmark image, for example one created by a high accuracy volume rendering system, the method can be used to evaluate the accuracy of a given image.

  8. Teachers and the foundations of intercultural interaction

    NASA Astrophysics Data System (ADS)

    Günay, Oya

    2016-08-01

    With the effects of globalisation, the number of people exposed to intercultural interaction has increased significantly. One of the most affected sectors is education. In parallel to the increase in numbers of students going abroad for tertiary education, primary and secondary education classes have also become culturally and religiously more diverse, mainly due to the effects of migration. With the increase in cultural diversity among their students, teachers find themselves facing new challenges. In order to be able to effectively encourage cultural exchange and intercultural dialogue, teachers need to cultivate their own intercultural competence. However, instead of directly jumping to the end result, this paper focuses on the very foundations of any intercultural interaction, namely self-awareness - of one's own normative settings -, acceptance of the equality of different cultural approaches, and strategies for how these can be transformed into personal attributes. The author highlights the importance of the internalisation of a belief in order to be able to reflect it in one's behaviour and convey to others the sense that they are genuinely accepted as they are. Self-Determination Theory (SDT) provides important insights into how and under which conditions internalisation can take place. Combining the insights gained from SDT with questioning techniques used by coaching experts, the author drafts a set of self-assessment questions which aim to help teachers reflect on the foundations of their intercultural interactions, gauge their level of internalisation and define the areas they have to focus on in order to cultivate their intercultural competence.

  9. Moral foundations vignettes: a standardized stimulus database of scenarios based on moral foundations theory.

    PubMed

    Clifford, Scott; Iyengar, Vijeth; Cabeza, Roberto; Sinnott-Armstrong, Walter

    2015-12-01

    Research on the emotional, cognitive, and social determinants of moral judgment has surged in recent years. The development of moral foundations theory (MFT) has played an important role, demonstrating the breadth of morality. Moral psychology has responded by investigating how different domains of moral judgment are shaped by a variety of psychological factors. Yet, the discipline lacks a validated set of moral violations that span the moral domain, creating a barrier to investigating influences on judgment and how their neural bases might vary across the moral domain. In this paper, we aim to fill this gap by developing and validating a large set of moral foundations vignettes (MFVs). Each vignette depicts a behavior violating a particular moral foundation and not others. The vignettes are controlled on many dimensions including syntactic structure and complexity making them suitable for neuroimaging research. We demonstrate the validity of our vignettes by examining respondents' classifications of moral violations, conducting exploratory and confirmatory factor analysis, and demonstrating the correspondence between the extracted factors and existing measures of the moral foundations. We expect that the MFVs will be beneficial for a wide variety of behavioral and neuroimaging investigations of moral cognition. PMID:25582811

  10. Moral foundations vignettes: a standardized stimulus database of scenarios based on moral foundations theory

    PubMed Central

    Iyengar, Vijeth; Cabeza, Roberto; Sinnott-Armstrong, Walter

    2016-01-01

    Research on the emotional, cognitive, and social determinants of moral judgment has surged in recent years. The development of moral foundations theory (MFT) has played an important role, demonstrating the breadth of morality. Moral psychology has responded by investigating how different domains of moral judgment are shaped by a variety of psychological factors. Yet, the discipline lacks a validated set of moral violations that span the moral domain, creating a barrier to investigating influences on judgment and how their neural bases might vary across the moral domain. In this paper, we aim to fill this gap by developing and validating a large set of moral foundations vignettes (MFVs). Each vignette depicts a behavior violating a particular moral foundation and not others. The vignettes are controlled on many dimensions including syntactic structure and complexity making them suitable for neuroimaging research. We demonstrate the validity of our vignettes by examining respondents’ classifications of moral violations, conducting exploratory and confirmatory factor analysis, and demonstrating the correspondence between the extracted factors and existing measures of the moral foundations. We expect that the MFVs will be beneficial for a wide variety of behavioral and neuroimaging investigations of moral cognition. PMID:25582811

  11. Moral foundations vignettes: a standardized stimulus database of scenarios based on moral foundations theory.

    PubMed

    Clifford, Scott; Iyengar, Vijeth; Cabeza, Roberto; Sinnott-Armstrong, Walter

    2015-12-01

    Research on the emotional, cognitive, and social determinants of moral judgment has surged in recent years. The development of moral foundations theory (MFT) has played an important role, demonstrating the breadth of morality. Moral psychology has responded by investigating how different domains of moral judgment are shaped by a variety of psychological factors. Yet, the discipline lacks a validated set of moral violations that span the moral domain, creating a barrier to investigating influences on judgment and how their neural bases might vary across the moral domain. In this paper, we aim to fill this gap by developing and validating a large set of moral foundations vignettes (MFVs). Each vignette depicts a behavior violating a particular moral foundation and not others. The vignettes are controlled on many dimensions including syntactic structure and complexity making them suitable for neuroimaging research. We demonstrate the validity of our vignettes by examining respondents' classifications of moral violations, conducting exploratory and confirmatory factor analysis, and demonstrating the correspondence between the extracted factors and existing measures of the moral foundations. We expect that the MFVs will be beneficial for a wide variety of behavioral and neuroimaging investigations of moral cognition.

  12. Another Foundation Goes to School: The Panasonic Foundation's School Restructuring Program.

    ERIC Educational Resources Information Center

    Sa, Sophie

    1992-01-01

    The Panasonic Foundation made the improvement of elementary and secondary education its primary mission. The article describes its partnership program which involved it in long-term, intensive relationships with urban school districts. Evaluation of the partnership indicates it has been central in promoting reflective thinking and educational…

  13. Foundational issues concerning taxa and taxon names.

    PubMed

    Ereshefsky, Marc

    2007-04-01

    In a series of articles, Rieppel (2005, Biol. Philos. 20:465-487; 2006a, Cladistics 22:186-197; 2006b, Systematist 26:5-9), Keller et al. (2003, Bot. Rev. 69:93-110), and Nixon and Carpenter (2000, Cladistics 16:298-318) criticize the philosophical foundations of the PhyloCode. They argue that species and higher taxa are not individuals, and they reject the view that taxon names are rigid designators. Furthermore, they charge supporters of the individuality thesis and rigid designator theory with assuming essentialism, committing logical inconsistencies, and offering proposals that render taxonomy untestable. These charges are unsound. Such charges turn on confusions over rigid designator theory and the distinction between kinds and individuals. In addition, Rieppel's, Keller et al.'s, and Nixon and Carpenter's proposed alternatives are no better and have their own problems. The individuality thesis and rigid designator theory should not be quickly abandoned. PMID:17464884

  14. Statistical foundations of liquid-crystal theory

    PubMed Central

    Seguin, Brian; Fried, Eliot

    2013-01-01

    We develop a mechanical theory for systems of rod-like particles. Central to our approach is the assumption that the external power expenditure for any subsystem of rods is independent of the underlying frame of reference. This assumption is used to derive the basic balance laws for forces and torques. By considering inertial forces on par with other forces, these laws hold relative to any frame of reference, inertial or noninertial. Finally, we introduce a simple set of constitutive relations to govern the interactions between rods and find restrictions necessary and sufficient for these laws to be consistent with thermodynamics. Our framework provides a foundation for a statistical mechanical derivation of the macroscopic balance laws governing liquid crystals. PMID:23772091

  15. Safety as a Foundation for Project Success

    SciTech Connect

    Schepens, R.J.; Wiegman, S.A.; Shrader, T.; Coleman, S.J.

    2006-07-01

    This paper describes the importance of safety as a foundation for success on the largest and most complex cleanup project in the DOE complex. It describes the breadth of safety considerations ranging from design of systems to prevent low probability large consequence events to the day-to-day work hazard analysis and accident prevention. We are developing many first of a kind systems for handling, treating and disposing of the nation's largest volume of stored radioactive and hazardous waste. It is stored in aging underground tanks distributed across nearly 100 square miles. The project includes the development of retrieval and transfer systems, treatment and product handling, storage and disposal. When considering safety for a project of this magnitude it is necessary to include knowledge from almost every discipline as the breadth of hazard is large. Line ownership, worker involvement, and open communication are keys to safety success. (authors)

  16. Expert Meeting Report: Foundations Research Results

    SciTech Connect

    Ojczyk, C.; Huelman, P.; Carmody, J.

    2013-05-01

    In the Expert Meeting Plan, the NorthernSTAR Team proposed to host two Expert Meetings in calendar year 2011. Invitees to the meetings would include experts in the current field of study, other BA team members, and representatives from DOE and NREL. They will invite leading industry experts to present at these meetings. The Expert Meetings will focus on key systems areas that will be required to meet the Building America performance goals and shall be sufficiently narrow in scope that specific conclusions, action items, and delegation of future tasks can be identified and completed. The two expert meeting topics are 'Foundations' and 'Window Retrofit.' The first session is designed as a webinar only and the second will be a live meeting.

  17. New Directions For Foundations In Health Equity.

    PubMed

    Doykos, Patricia; Gray-Akpa, Kristina; Mitchell, Faith

    2016-08-01

    Rising income inequality and pessimism about the current and future status of race relations in the United States make this both a challenging time for the pursuit of health equity and also an important opportunity for action. We glean lessons from past and ongoing philanthropic investments in health equity and recommend approaches that can guide future work by foundations. Improving health equity is a complex process that must take into account a variety of factors that affect health, of which access to high-quality health care is just one element. Accordingly, improving health equity will require the combined forces of philanthropy, the public sector, and sectors that have not traditionally been identified with health. PMID:27503980

  18. Physical Foundations of Self-organizing Systems

    NASA Astrophysics Data System (ADS)

    Chatterjee, Atanu; Georgiev, Georgi

    2014-03-01

    The appearance of coherent global pattern due to local interactions is known as self-organization. Self-organization is a spontaneous process in highly non-equilibrium dissipative systems that form structures which tend to maximize energy dissipation by leveling off energy gradients. This follows as a direct consequence of the Second Law of Thermodynamics. Also, a local interaction embodies in the above definition a mechanistic dimension to self-organization. The link between mechanics and the Second Law of Thermodynamics lie in the Principle of Least Action, a strong law of nature that is obeyed in every spontaneous process. Thus, self-organization rests on two basic foundational principles of nature namely, the Second Law of Thermodynamics and the Principle of Least Action. We attempt to develop a formal definition of self-organization based on those principles.

  19. Foundations for a natural science of philosophy

    PubMed Central

    Fraley, Lawrence E.

    1999-01-01

    The functional relations among philosophy, science, technology, and intuition are examined. Those domains are each defined as behaviors, and each of them is then classified either as verbal, nonverbal, or both. Finally, those classes of behavior are organized into one integral behavioral system. The concept of a science of philosophy is introduced. A science and technology of philosophy are not only possible but necessary. Such an approach to the discipline of philosophy could lead to a new disciplinary structure for philosophy. Philosophy could be taught in academic departments as a verbal behavioral science. The discipline of behaviorology provides the foundations necessary to capacitate the traditional discipline of philosophy as a science and technology of verbal behavior commensurate with its potential cultural mission. PMID:22477161

  20. Information architecture. Volume 1, The foundations

    SciTech Connect

    1995-03-01

    The Information Management Planning and Architecture Coordinating Team was formed to establish an information architecture framework to meet DOE`s current and future information needs. This department- wide activity was initiated in accordance with the DOE Information Management Strategic Plan; it also supports the Departmental Strategic Plan. It recognizes recent changes in emphasis as reflected in OMB Circular A-130 and the Information Resources Management Planning Process Improvement Team recommendations. Sections of this document provides the foundation for establishing DOE`s Information Architecture: Background, Business Case (reduced duplication of effort, increased integration of activities, improved operational capabilities), Baseline (technology baseline currently in place within DOE), Vision (guiding principles for future DOE Information Architecture), Standards Process, Policy and Process Integration (describes relations between information architecture and business processes), and Next Steps. Following each section is a scenario. A glossary of terms is provided.