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1.
2.
We address several conjectures raised in Cantrell et al. [Evolution of dispersal and ideal free distribution, Math. Biosci. Eng. 7 (2010), pp. 17–36 [9 Cantrell, R. S., Cosner, C. and Lou, Y. 2010. Evolution of dispersal and ideal free distribution. Math. Biosci. Eng., 7: 1736. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]]] concerning the dynamics of a diffusion–advection–competition model for two competing species. A conditional dispersal strategy, which results in the ideal free distribution of a single population at equilibrium, was found in Cantrell et al. [9 Cantrell, R. S., Cosner, C. and Lou, Y. 2010. Evolution of dispersal and ideal free distribution. Math. Biosci. Eng., 7: 1736. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]]. It was shown in [9 Cantrell, R. S., Cosner, C. and Lou, Y. 2010. Evolution of dispersal and ideal free distribution. Math. Biosci. Eng., 7: 1736. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]] that this special dispersal strategy is a local evolutionarily stable strategy (ESS) when the random diffusion rates of the two species are equal, and here we show that it is a global ESS for arbitrary random diffusion rates. The conditions in [9 Cantrell, R. S., Cosner, C. and Lou, Y. 2010. Evolution of dispersal and ideal free distribution. Math. Biosci. Eng., 7: 1736. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]] for the coexistence of two species are substantially improved. Finally, we show that this special dispersal strategy is not globally convergent stable for certain resource functions, in contrast with the result from [9 Cantrell, R. S., Cosner, C. and Lou, Y. 2010. Evolution of dispersal and ideal free distribution. Math. Biosci. Eng., 7: 1736. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]], which roughly says that this dispersal strategy is globally convergent stable for any monotone resource function.  相似文献   

3.
This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[1 Noll, D.M.; McG.Mason, T.; Miller, P.S. Formation and repair of interstrand cross-links in DNA. Chem. Rev. 2006, 106, 277301.[Crossref], [PubMed], [Web of Science ®] [Google Scholar],2 Rink, S.M.; Hopkins, P.B. Direct evidence for DNA intrastrand cross-linking by the nitrogen mustard mechlorethamine in synthetic oligonucleotides. Bioorg. Med. Chem. Lett. 1995, 5(23), 28452850.[Crossref], [Web of Science ®] [Google Scholar],3 Chabner, B.A.; Collins, J.M. Cancer Chemotherapy: Principles and Practices, PA, J.B. Lippincott Company, Philadelphia, 1990, pp. 276313. [Google Scholar]]triazole, showed an interesting cytotoxic effect.  相似文献   

4.
Recent adaptationist accounts of human mental and physical health have reinvigorated the debate over the evolution of human intelligence. In the tradition of strong inference the current study was developed to determine whether either Miller's (1998 Miller, G. F. 1998. “How mate choice shaped human nature: A review of sexual selection and human evolution”. In Handbook of evolutionary psychology: Ideas, issues, and applications, Edited by: Crawford, C. and Krebs, D. 87129. Hillsdale, NJ: Lawrence Erlbaum.  [Google Scholar], 2000a Miller, G. F. 2000a. Mental traits as fitness indicators: Expanding evolutionary psychology's adaptationism. Evolutionary approaches to human reproductive behavior. Ann N Y Acad Sci, 907: 6274. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]) Fitness Indicator Theory or Rushton's (1985 Rushton, J. P. 1985. Differential K theory: The sociobiology of individual and group differences. Pers Indiv Diff, 6(4): 441452. [Crossref] [Google Scholar], 2000 Rushton, J. P. 2000. Race, evolution, and behavior: A life-history perspective, 3rd, Port Huron, MI: Charles Darwin Research Institute.  [Google Scholar]) Differential-K Theory better accounts for general intelligence (“g”) in an undergraduate university population (N = 192). Owing to the lengthy administration time of the test materials, a newly developed 18-item short form of the Ravens Advanced Progressive Matrices (APM-18; Sefcek, Miller, and Figueredo 2007 Sefcek, J. A., Miller, G. F. and Figueredo, A. J. 2007. “Development and of an 18-item short form of the Ravens Advanced Progressive Matrices (RAPM-18). (Submitted)”.  [Google Scholar]) was used. A significant, positive relationship between K and F (r = .31, p < .001) emerged. Contrary to predictions, no significant relationships were found between “g” and either K or F (r = –.09, p ≥ .05 and r = .11, p ≥ .05, respectively). Though generally contrary to both hypotheses, these results may be explained in relation to antagonistic pleiotropy and a potential failure to derive correct predictions for within-species comparisons directly from the results of between-species comparisons.  相似文献   

5.
The Divakar-Reese procedure has been successfully applied for transforming 7-oxo-isothiazolo[4,5-d]pyrimidine C-nucleosides (4a,b, 5a,b, 6a) via 1,2,4-triazol-1-yl intermediates (7a,b, 8a,b) into various 7-substituted C-nucle- osides 15a,b, 16a,b, 17a, 18a, 19a,b, 20a,b; their subsequent deprotection provides novel types of unusual C-glycosides 22b, 23a, 24a,b, 25b, 26b.

C-Nucleosides, possessing on its heterocyclic base other than naturally occuring oxo- or amino substituents, are important model compounds for biological or medicinal studies [2a] Hanessian, S. and Pernet, A. G. 1976. Adv. Carbohydr. Chem. Biochem., 32: 111188. cf. [Google Scholar], [2b] Mizuno, Y. 1986. The Organic Chemistry of Nucleic Acids Amsterdam: Elsevier.  [Google Scholar], [2c] Huryn, D. M. and Okabe, M. 1992. Chem. Rev., 92: 17451768. [Crossref], [Web of Science ®] [Google Scholar], [2d] Häbich, D. 1991. Chem. in uns. Zeit, 25: 295307.  [Google Scholar], [2e] Uhlmann, E. and Peyman, A. 1990. Chem. Rev., 90: 543584. [Crossref], [Web of Science ®] [Google Scholar], [2f] Thuong, N. T. and Helene, C. 1993. Angew. Chem., 105: 697723. [Crossref] [Google Scholar], [2g] 1993. Angew. Chem. Int. Ed. Engl., 33: 666690.  [Google Scholar], [2h] Yarchoan, R., Mitsuya, H., Zhomas, R. V., Pluda, J. M., Hartman, N. R., Perno, C. F., Marczyk, K. S., Allain, J. P., Johns, D. G. and Broder, S. 1989. Science, 245: 412414. [Crossref], [PubMed], [Web of Science ®] [Google Scholar], [2i] Tanaka, H., Baba, M., Hayakawa, H., Sakamaki, T., Miyasaka, T., Ubasawa, M., Takashima, H., Sekiya, E., Nitta, I., Shigeta, S., Walker, R. T., Balzarini, J. and De Clerq, E. 1991. J. Med. Chem., 34: 349357. [Crossref], [PubMed], [Web of Science ®] [Google Scholar] [3a] Koyama, G., Maeda, K., Umezawa, H. and Iitaka, Y. 1966. Tetrahedron Lett., : 597602. Some C-glycosides with antibiotic, antiviral (HIV), and anticancer activities [Google Scholar], [3b] Hori, M., Wakashiro, T., Ito, E., Sawa, T., Takeuchi, T. and Umezawa, H. J. 1968. J. Antibiot., 21A: 264270. [Chem. Abstr. 1968, 69, 11356j] [Google Scholar], [3c] Farkas, J. and ?orm. 1972. F. Collect. Czech. Chem. Commun., 37: 27982803.  [Google Scholar], [3d] Acton, E. M., Ryan, K. J., Henry, D. W. and Goodman, L. 1971. J. Chem. Soc., Chem. Commun., : 986988.  [Google Scholar], [3e] Nakagawa, Y., Kano, H., Tsukuda, Y. and Koyama, H. 1967. Tetrahedron Lett., : 41054109.  [Google Scholar], [3f] Inoue, I. and Kuwaijama, I. 1980. J. Chem. Soc., Chem. Commun., : 251253.  [Google Scholar], [3g] Buchanan, J. G., Stobie, A. and Wightman, R. H. 1980. ibid., : 916917. [Crossref] [Google Scholar], [3h] Hildebrand, S. and Leumann, C. 1996. Angew. Chem., 108: 21002102. Angew. Chem. Int. Ed. Engl. 1996, 35, 1968–1970 [Google Scholar]. We want to report on the synthesis of novel 7-substituted isothiazolo = [4,5-d]pyrimidine C-nucleosides. As we could show in previous papers [1] Wamhoff, H., Berressem, R. and Nieger, M. 1994. J. Org. Chem., 59: 19121917. Part 2 [Google Scholar], [4] Wamhoff, H., Berressem, R. and Nieger. 1993. M. J. Org. Chem., 58: 51815185.  [Google Scholar], there exists a simple approach to the protected C-glycosides 46.

  相似文献   

6.
Theory, research, and application in developmental science share the conceptual and methodological challenges of integrating the study of the course of a person's intra-individual changes and the formulation of subgroup (differential) or nomothetic generalizations. One approach to these challenges has involved building tailored construct representations that filter out irrelevant idiosyncratic information hampering the articulation of nomothetic relations by means of individual level factor analysis (P–technique). Exploring this approach has provided initially promising results (Nesselroade, Gerstorf, Hardy, & Ram, 2007 Nesselroade , J. R. , Gerstorf , D. , Hardy , S. A. , & Ram , N. ( 2007 ). Idiographic filters for psychological constructs . Measurement: Interdisciplinary Research and Perspectives , 5 , 217235 . doi: DOI: 10.1080/15366360701741807 [Taylor & Francis Online] [Google Scholar]). We present a specification of an alternative to traditional factor invariance (higher-order invariance) that further formalizes these ideas and examine the results of some simulation experiments designed to evaluate the appropriateness of the implementation. The results also have implications for use in basic and applied work across the life span of between-persons variation and subgroup comparisons to establish relations among variables.  相似文献   

7.
Tyrosine phosphorylation is rare, representing only about 0.5% of phosphorylations in the cell under basal conditions. While mitogenic tyrosine kinase signaling has been extensively explored, the role of phosphotyrosine signaling across the cell cycle and in particular during mitosis is poorly understood.

Two recent, independent studies tackled this question from different angles to reveal exciting new insights into the role of this modification during cell division. Caron et al.1 Caron D, Byrne DP, Thebault P, Soulet D, Landry CR, Eyers PA, Elowe S. Mitotic phosphotyrosine network analysis reveals that tyrosine phosphorylation regulates Polo-like kinase 1 (PLK1). Sci Signal 2016; 9:rs14; PMID:27965426; http://dx.doi.org/10.1126/scisignal.aah3525[Crossref], [PubMed], [Web of Science ®] [Google Scholar] exploited mitotic phosphoproteomics data sets to determine the extent of mitotic tyrosine phosphorylation, and St-Denis et al.2 St-Denis N, Gupta GD, Lin ZY, Gonzalez-Badillo B, Veri AO, Knight JD, Rajendran D, Couzens AL, Currie KW, Tkach JM, et al. Phenotypic and interaction profiling of the human phosphatases identifies diverse mitotic regulators. Cell Rep 2016; 17:2488-501; PMID:27880917; http://dx.doi.org/10.1016/j.celrep.2016.10.078[Crossref], [PubMed], [Web of Science ®] [Google Scholar] identified protein tyrosine phosphatases from all subfamilies as regulators of mitotic progression or spindle formation. These studied collectively revealed that tyrosine phosphorylation may play a more prominent and active role in mitotic progression than previously appreciated.  相似文献   


8.
Ilya V. Buynevich 《Ichnos》2013,20(4):189-191
Recognition and sampling of traces in unconsolidated sands present a major challenge for ichnologists. This can be partially remedied through the application of high-resolution geophysical techniques, such as ground-penetrating radar (GPR or georadar), which uses electromagnetic impulse for continuous imaging of shallow subsurface. It addition to geological applications, GPR imaging has been used in several studies focused on animal traces as related to conservation of endangered fossorial species (Kinlaw et al., 2007 Kinlaw, A. E., Conyers, L. B. and Zajac, W. 2007. Use of ground penetrating radar to image burrows of the gopher tortoise (Gopherus polyphemus). Herpetological Review, 38: 5056.  [Google Scholar]; Martin et al., 2011 Martin, A. J., Skaggs, S. A., Vance, R. K. and Greco, V. 2011. Ground-penetrating radar investigation of gopher-tortoise burrows: Refining the characterization of modern vertebrate burrows and associated commensal traces. Geological Society of America Abstracts with Programs, 43: 381 [Google Scholar]), slope and levee stability (Nichol et al., 2003 Nichol, D., Lenham, J. W. and Reynolds, J. M. 2003. Application of ground-penetrating radar to investigate the effects of badger setts on slope stability at St. Asaph Bypass, North Wales. Quarterly Journal of Engineering Geology and Hydrogeology, 36: 143153.  [Google Scholar]; Di Prinzio et al., 2010 Di Prinzio, M, Bittelli, M., Castellarin, A. and Pisa, P. R. 2010. Application of GPR to the monitoring of river embankments. Journal of Applied Geophysics, 7: 5361.  [Google Scholar]), and mapping of fossil tracks (Matthews et al., 2006 Matthews, N. A., Noble, T. A. and Breithaupt, B. H. 2006. “The application of photogrammetry, remote sensing and geographic information systems (GIS) to fossil resource management”. In Fossils from Federal Lands, Edited by: Lucas, S. G., Spielmann, J. A., Hester, P. M., Kenworthy, J. P. and Santucci, V. L. Vol. 34, 119131. New Mexico Museum of Natural History and Science Bulletin.  [Google Scholar]; Aucoin and Hasbargen, 2010 Aucoin, C. D. and Hasbargen, L. 2010. Using GPR, GPS and close-range photography to map and characterize dinosaur tracks in the Connecticut River valley. Geological Society of America Abstracts with Programs, 42: 276 [Google Scholar]) and tracking surfaces (Webb, 2007 Webb, S. 2007. Further research of the Willandra Lakes fossil footprint site, southeastern Australia. Journal of Human Evolution, 52: 711715. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]). Few efforts have been dedicated specifically to characterizing burrow and track characteristics (Stott, 1996 Stott, P. 1996. Ground-penetrating radar: a technique for investigating the burrow structure of fossorial vertebrates. Wildlife Research, 22: 519530.  [Google Scholar]; Sensors & Software Inc., 2010 [compilation on geophysical projects related to animal burrows]; Buynevich and Hasiotis, 2011; Buynevich et al., 2011; Martin et al., 2011) and most of the above studies are published in journals not routinely accessed by ichnologists.  相似文献   

9.

Copper(I)-catalyzed 5-endo-dig cyclizations of 5-(alkyn-1-yl)uracil derivatives had given poor yields of substituted furo[2 Robins, M. J. and Barr, P. J. 1983. Nucleic acid related compounds. 39. Efficient conversion of 5-iodo to 5-alkynyl and derived 5-substituted uracil bases and nucleosides. J. Org. Chem, 48: 18541862. [CSA][CROSSREF][Crossref], [Web of Science ®] [Google Scholar], 3 De Clercq, E., Descamps, J., Balzarini, J., Giziewicz, J., Barr, P. J. and Robins, M. J. 1983. Nucleic acid related compounds. 40. Synthesis and biological activities of 5-alkynyluracil nucleosides. J. Med. Chem, 26: 661666. [PUBMED][INFOTRIEVE][CSA][CROSSREF][Crossref], [PubMed], [Web of Science ®] [Google Scholar]]pyrimidin-2-ones unless the uracil ring was substituted at N1 with alkyl or glycosyl groups. This limited flexibility for the synthesis of analogues with varied substituents at N3 and/or C6 of the furo[2 Robins, M. J. and Barr, P. J. 1983. Nucleic acid related compounds. 39. Efficient conversion of 5-iodo to 5-alkynyl and derived 5-substituted uracil bases and nucleosides. J. Org. Chem, 48: 18541862. [CSA][CROSSREF][Crossref], [Web of Science ®] [Google Scholar], 3 De Clercq, E., Descamps, J., Balzarini, J., Giziewicz, J., Barr, P. J. and Robins, M. J. 1983. Nucleic acid related compounds. 40. Synthesis and biological activities of 5-alkynyluracil nucleosides. J. Med. Chem, 26: 661666. [PUBMED][INFOTRIEVE][CSA][CROSSREF][Crossref], [PubMed], [Web of Science ®] [Google Scholar]]pyrimidin-2-one core has been overcome with 5-(3-hydroxyalkyn-1-yl)uracil compounds with no substituent at N1. Manipulation of the side-chain hydroxyl group gives access to additional furo[2,3-d]pyrimidin-2-one analogues.  相似文献   

10.
Abstract

A new ichnofossiliferous locality in Salta Province (northwest Argentina) contains an association with numerous irregular spiral traces assigned to Spirodesmos milanai n. isp., in mature sandstones and quartzites with rippled bedding surfaces, rare wavy lamination and cross-bedded stratification. This record of early spiral behavior is interpreted as a primitive grazing method formed on muddy laminae above sand layers, and is related to a feeding strategy of an annelid-type of organism. Associated traces are Cruziana cf. semiplicata, Diplocraterion isp., Monocraterion isp., Rusophycus isp., Skolithos linearis Haldeman and Skolithos magnus Howell. The ichnoassemblage is similar to a shallow-water ichnoassociation from the Permian Ecca Group of South Africa (Mason et al., 1983 Mason, T. R., Stanistreet, I. G. and Tavener-Smith, R. 1983. Spiral trace fossils from the Permian Ecca Group of Zululand. Lethaia, 16: 241247. [Crossref], [Web of Science ®] [Google Scholar]).  相似文献   

11.
《朊病毒》2013,7(6):405-411
ABSTRACT

Within the mammalian prion field, the existence of recombinant prion protein (PrP) conformers with self-replicating (ie. autocatalytic) activity in vitro but little to no infectious activity in vivo challenges a key prediction of the protein-only hypothesis of prion replication – that autocatalytic PrP conformers should be infectious. To understand this dissociation of autocatalysis from infectivity, we recently performed a structural and functional comparison between a highly infectious and non-infectious pair of autocatalytic recombinant PrP conformers derived from the same initial prion strain.1 Noble GP, Wang DW, Walsh DJ, Barone JR, Miller MB, Nishina KA, Li S, Supattapone S. A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers. PLoS Pathog 2015; 11:e1005017; PMID:26125623; http://dx.doi.org/10.1371/journal.ppat.1005017[Crossref], [PubMed], [Web of Science ®] [Google Scholar] We identified restricted, C-terminal structural differences between these 2 conformers and provided evidence that these relatively subtle differences prevent the non-infectious conformer from templating the conversion of native PrPC substrates containing a glycosylphosphatidylinositol (GPI) anchor.1 Noble GP, Wang DW, Walsh DJ, Barone JR, Miller MB, Nishina KA, Li S, Supattapone S. A Structural and Functional Comparison Between Infectious and Non-Infectious Autocatalytic Recombinant PrP Conformers. PLoS Pathog 2015; 11:e1005017; PMID:26125623; http://dx.doi.org/10.1371/journal.ppat.1005017[Crossref], [PubMed], [Web of Science ®] [Google Scholar] In this article we discuss a model, consistent with these findings, in which recombinant PrP, lacking post-translational modifications and associated folding constraints, is capable of adopting a wide variety of autocatalytic conformations. Only a subset of these recombinant conformers can be adopted by post-translationally modified native PrPC, and this subset represents the recombinant conformers with high specific infectivity. We examine this model's implications for the generation of highly infectious recombinant prions and the protein-only hypothesis of prion replication.  相似文献   

12.
Sequestration of aggregates into specialized deposition sites occurs in many species across all kingdoms of life ranging from bacteria to mammals and is commonly believed to have a cytoprotective function. Yeast cells possess at least 3 different spatially separated deposition sites, one of which is termed “Insoluble Protein Deposit (IPOD)” and harbors amyloid aggregates. We have recently discovered that recruitment of amyloid aggregates to the IPOD uses an actin cable based recruitment machinery that also involves vesicular transport.1 Kumar R, Nawroth PP, Tyedmers J. Prion aggregates are recruited to the insoluble protein deposit (IPOD) via myosin 2-based vesicular transport. PLoS Genet 2016; 12:e1006324; PMID:27689885; http://dx.doi.org/10.1371/journal.pgen.1006324[Crossref], [PubMed], [Web of Science ®] [Google Scholar] Here we discuss how different proteins known to be involved in vesicular transport processes to the vacuole might act to guide amyloid aggregates to the IPOD. These factors include the Myosin V motor protein Myo2 involved in transporting vacuolar vesicles along actin cables, the transmembrane protein Atg9 involved in the recruitment of large precursor hydrolase complexes to the vacuole, the phosphatidylinositol/ phosphatidylcholine (PI/PC) transfer protein Sec 14 and the SNARE chaperone Sec 18. Furthermore, we present new data suggesting that the yeast dynamin homolog Vps1 is also crucial for faithful delivery of the amyloid model protein PrD-GFP to the IPOD. This is in agreement with a previously identified role for Vps1 in recruitment of heat-denatured aggregates to a perivacuolar deposition site.2 Hill SM, Hao X, Gronvall J, Spikings-Nordby S, Widlund PO, Amen T, Jörhov A, Josefson R, Kaganovich D, Liu B, et al. Asymmetric inheritance of aggregated proteins and age reset in yeast are regulated by Vac17-dependent vacuolar functions. Cell Rep 2016; 16:826-38; PMID:27373154[Crossref], [PubMed], [Web of Science ®] [Google Scholar]  相似文献   

13.
Methamphetamine (METH) abuse is a major threat in the USA and worldwide without any FDA approved medications. Anti-METH antibody antagonists block or slow the rate of METH entry into the brain and have shown efficacy in preclinical studies (Peterson, Laurenzana, Atchley, Hendrickson, & Owens, 2008 Peterson, E. C., Laurenzana, E. M., Atchley, W. T., Hendrickson, H. P. and Owens, S. M. 2008. Development and preclinical testing of a high-affinity single-chain antibody against (+)-methamphetamine. Journal of Pharmacology and Experimental Therapeutics, 08: 124133.  [Google Scholar]).?A key determinant of the antibody’s efficacy is its affinity for METH and we attempted to enhance the efficacy by designing mutations to alter the shape or the electrostatic character of the binding pocket. Towards this goal, we developed a single chain anti-METH antibody fragment (scFv6H4) from a parent IgG (1). The crystal structure of scFv-6H4 in complex with METH was determined (Celikel, Peterson, Owens, & Varughese, 2009 Celikel, R., Peterson, E. C., Owens, S. M. and Varughese, K. I. 2009. Crystal structures of a therapeutic single chain antibody in complex with two drugs of abuse-Methamphetamine and 3,4-methylenedioxymethamphetamine. Protein Science, 09: 23362345.  [Google Scholar]). Based on its elucidated binding interactions, we designed point mutations in the binding pocket to improve its affinity for METH and amphetamine (AMP), the active metabolite of METH. The mutants, scFv-S93T,-I37?M and -Y34?M were cloned, expressed in yeast and tested for affinity against METH and AMP. Two mutants showed enhanced binding affinity for METH: scFv-I37?M by 1.3-fold and scFv-S93T by 2.6-fold. Additionally, all the mutants showed increase in affinity for AMP: scFv-I37?M by 56-fold, scFv-S93T by 17-fold and scFvY34?M by 5-fold. Crystal structure for one of the high-affinity mutant, scFv-S93T, in complex with METH was determined (Figure 1). Binding pocket of the mutant is more hydrophobic in comparison with the wild type. ScFv-6H4 binds METH in a deep pocket containing two water molecules. The substitution of a serine residue by a threonine leads to the expulsion of a water molecule (Figure 2), relieving some unfavorable contacts between the hydrocarbon atoms of METH and the water molecule and increasing the affinity to sub-nanomolar range. Therefore, the present study shows that efficacy could be enhanced by altering the hydrophobicity or the shape of the binding pocket.  相似文献   

14.
After central nervous system (CNS) insults, such as spinal cord injury or traumatic brain injury, neurons encounter a complex microenvironment where mechanisms that promote regeneration compete with inhibitory processes. Sprouting and axonal re-growth are key components of functional recovery, but are often counteracted by inhibitory molecules. Several strategies are being pursued whereby these inhibitory molecules are either being neutralized with blocking antibodies, with enzymatic degradation or downstream signaling events are being interfered with. Two recent studies1 Tan CL, Andrews MR, Kwok JC, Heintz TG, Gumy LF, Fässler R, et al. Kindlin-1 enhances axon growth on inhibitory chondroitin sulfate proteoglycans and promotes sensory axon regeneration. J Neurosci 2012; 32:7325 - 35; http://dx.doi.org/10.1523/JNEUROSCI.5472-11.2012; PMID: 22623678 [Crossref], [PubMed], [Web of Science ®] [Google Scholar],2 Tan CL, Kwok JC, Patani R, Ffrench-Constant C, Chandran S, Fawcett JW. Integrin activation promotes axon growth on inhibitory chondroitin sulfate proteoglycans by enhancing integrin signaling. J Neurosci 2011; 31:6289 - 95; http://dx.doi.org/10.1523/JNEUROSCI.0008-11.2011; PMID: 21525268 [Crossref], [PubMed], [Web of Science ®] [Google Scholar] show that activating integrin signaling in dorsal root ganglion (DRG) neurons renders them able to overcome inhibitory signals, and could possibly lead to new strategies to improve neuronal regeneration.  相似文献   

15.
16.
We investigated the morphology, morphogenesis and small subunit rRNA gene-based phylogeny of three marine urostylids, Uncinata gigantea Bullington, 1940 Bullington, W. E. (1940). Some ciliates from Tortugas. Papers from the Tortugas Laboratory, 32, 179221. [Google Scholar], Holosticha heterofoissneri Hu & Song, 2001 Hu, X., & Song, W. (2001). Morphology and morphogenesis of Holosticha heterofoissneri n. sp. from the Yellow Sea, China (Ciliophora, Hypotrichida). Hydrobiologia, 448, 171179. doi:10.1023/A:1017553406031.[Crossref], [Web of Science ®] [Google Scholar], and Holosticha cf. heterofoissneri. The dorsal morphogenesis of Uncinata gigantea shows de novo formation of two groups of anlagen near the marginal rows. Holosticha cf. heterofoissneri demonstrates fragmentation of the first dorsal kinety anlage as in Holosticha heterofoissneri. Our population of H. heterofoissneri corresponds well with previously described populations in terms of its general morphology and ciliary pattern. Uncinata gigantea can be recognized by its large and highly contractile body, yellowish to brownish cell colour, two types of cortical granules, and 20–30 transversely oriented and densely arranged cirri in the left marginal row, which often overlie the buccal vertex. Based on the new data, especially infraciliature, the genus Uncinata is here redefined. Both the morphology and phylogenetic analyses suggest that the genus Uncinata should be classified within the family Urostylidae. In addition, both morphological and morphogenetic data suggest that Holosticha bradburyae Gong et al., 2001 Gong, J., Song, W., Hu, X., Ma, H., & Zhu, M. (2001). Morphology and infraciliature of Holosticha bradburyae n. sp. (Ciliophora, Hypotrichida) from the Yellow Sea, China. Hydrobiologia, 464, 6369. doi:10.1023/A:1013901621439.[Crossref], [Web of Science ®] [Google Scholar] should be transferred to Uncinata as U. bradburyae (Gong et al., 2001 Gong, J., Song, W., Hu, X., Ma, H., & Zhu, M. (2001). Morphology and infraciliature of Holosticha bradburyae n. sp. (Ciliophora, Hypotrichida) from the Yellow Sea, China. Hydrobiologia, 464, 6369. doi:10.1023/A:1013901621439.[Crossref], [Web of Science ®] [Google Scholar]) comb. nov., due to its possession of a characteristically prominent beak-like, leftwards curved projection and the developmental mode of the dorsal kineties. This assignment is supported by the phylogenetic analyses, which placed Uncinata gigantea in a clade with U. bradburyae (Gong et al., 2001 Gong, J., Song, W., Hu, X., Ma, H., & Zhu, M. (2001). Morphology and infraciliature of Holosticha bradburyae n. sp. (Ciliophora, Hypotrichida) from the Yellow Sea, China. Hydrobiologia, 464, 6369. doi:10.1023/A:1013901621439.[Crossref], [Web of Science ®] [Google Scholar]) comb. nov., and revealed only 1.13% (19 bp) difference in their SSU-rDNA gene sequence.  相似文献   

17.
Abstract

Two series of novel fluorinated nucleosides dimers with an unnatural 1,2,3-triazole linkage were synthesized. The obtained molecules were prepared using “click” chemistry approach based on copper(I) catalyzed Huisgen azide–alkyne cycloaddition. It was performed between 3′- and 5′-azido-nucleosides as the azide components, and the 3′-O- and 5′-O-propargyl-nucleosides as the alkyne components. Based on analysis of the 3 Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. [Google Scholar]JHH, 3 Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. [Google Scholar]JH1′C2 and 3 Brunton, L. L.; Lazo, J. S.; Parker, K. L. (Eds.), Goodman & Gilman’s the Pharmacological Basis of Therapeutics, 11th ed.; McGraw-Hill, Medical Publishing Division: New York, NY, 2006. [Google Scholar]JH1′C6 we estimated conformational preferences of sugar part and orientation around glycosidic bond. All described nucleosides dimers analogs were characterized by spectroscopic methods and evaluated for their in vitro cytotoxicity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).  相似文献   

18.
An automated, iterative approach to finding the lowest energy, ionic diffusion paths through a periodic structure has been developed within our new code (written in FORTRAN 77 and named Bubble). The approach is quite general in that it can be applied to find, at a chosen temperature, the accessible (ergodic) regions of a hyper-surface, which is defined across a uniform grid [1 Schön, J.C., Putz, H. and Jansen, M. 1996. Studying the energy hypersurface of continuous system—The threshold algorithm. J. Phys.-Conden. Matt., 8: 143[Crossref] [Google Scholar]]. We describe both our implementation within the Bubble code and its application to locating the approximate transition states for Mg interstitial diffusion in forsterite, which can then be refined using standard transition state searching [2 Banerjee, A., Adams, N., Simons, J. and Shepard, R. 1985. Search for stationary points on surfaces. J. Phys. Chem., 89: 52[Crossref], [Web of Science ®] [Google Scholar]].  相似文献   

19.
In Disney/Pixar's phenomenally popular animated film Finding Nemo (Stanton, 2003 Stanton, A. Writer/Director. 2003. Finding Nemo [Motion picture], United States: Pixar Animation Studios.  [Google Scholar]), one of the central themes of fish welfare was highlighted when the moorish idol, Gill, commented, “Fish aren't meant to be kept in a box, kid. It does things to you.” The notion that fish might have the capacity to suffer in captivity (Chandroo, Duncan, & Moccia, 2004a Chandroo, K. P., Duncan, I. J. H and Moccia, R. D. 2004a. Can fish suffer?: Perspectives on sentience, pain, fear and stress. Applied Animal Behaviour Science, 86: 225250. [Crossref], [Web of Science ®] [Google Scholar], 2004b Chandroo, K. P., Duncan, I. J. H and Moccia, R. D. 2004b. An evaluation of current perspectives on consciousness and pain in fish. Fish and Fisheries, 5: 281295. [Crossref], [Web of Science ®] [Google Scholar]) links to the larger question of sentiency, which remains a fundamental tenet when justifying concerns for nonhuman animal welfare (Dawkins, 2006 Dawkins, M. S. 2006. Through animal eyes: What behaviour tells us. Applied Animal Behaviour Science, 100: 410. [Crossref], [Web of Science ®] [Google Scholar]; Huntingford et al., 2006 Huntingford, F. A., Adams, C., Braithwaite, V. A., Kadri, S., Pottinger, T. G.Sandoe, P. 2006. Review paper: Current issues in fish welfare. Journal of Fish Biology, 68: 332372. [Crossref], [Web of Science ®] [Google Scholar]). Although terrestrial nonhuman-animal welfare has been discussed and explored for many years, the development of aquatic animal welfare concepts and approaches remains relatively new and beyond public awareness (Braastad, Damsgård, & Juell, 2006; Broom, 2007 Broom, D. M. 2007. Cognitive ability and sentience: Which aquatic animals should be protected?. Disease of Aquatic Organisms, 75: 99108. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]; Farmed Animal Welfare Council, 1996; Fisheries Society of the British Isles, 2002; Håstein, Scarfe, & Lund, 2005; Iwama, 2007 Iwama, G. K. 2007. The welfare of fish. Diseases of Aquatic Organisms, 75: 155158. [Crossref], [PubMed], [Web of Science ®] [Google Scholar]; Schreck, 1981 Schreck, C. B. 1981. “Stress and compensation in teleostean fishes: Response to social and physical factors”. In Stress and fish, Edited by: Pickering, A. D. 295321. London: Academic.  [Google Scholar]).  相似文献   

20.
The abandoned Phillips sulfide mine in the critical Highlands watershed in New York has been shown to produce strongly acidic mine drainage (AMD) with anomalous metal contaminants in first-order streams that exceeded local water standards by up to several orders of magnitude (Gilchrist et al., 2009 Gilchrist, S., Gates, A., Szabo, Z. and Lamothe, P. J. 2009. Impact of AMD on water quality in critical watershed in the Hudson River drainage basin: Phillips Mine, Hudson Highlands, New York. Environ. Geol., 57: 397409. [Crossref], [Web of Science ®] [Google Scholar]). The metal-sulfide-rich tailings also produce contaminated soils with pH < 4, organic matter < 2.5% and trace metals sequestered in soil oxides. A geochemical transect to test worst-case soil contamination showed that Cr, Co and Ni correlated positively with Mn, (r = 0.72, r = 0.89, r = 0.80, respectively), suggesting Mn-oxide sequestration and that Cu and Pb correlated with Fe (r = 0.76, r = 0.83, respectively), suggesting sequestration in goethite. Ubiquitous, yellow coating on the mine wastes, including jarosite and goethite, is a carrier of the metals. Geochemical and μ-SXRF analyses determined Cu to be the major soil contaminant. μ-SXRF also demonstrated that the heterogeneous nature of the soil chemistry at the micro-meter scale is self-similar to those in the bulk soil samples. Generally metals decreased, with some fluctuations, rapidly downslope through suspension of fines and dissolution in AMD leaving the area of substantial contamination << 0.5 km from the source.  相似文献   

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