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  • 1
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    A nucleoside transporter from Trypanosoma brucei involved in drug resistance (1999)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1999-07-10
    Description: Drug resistance of pathogens is an increasing problem whose underlying mechanisms are not fully understood. Cellular uptake of the major drugs against Trypanosoma brucei spp., the causative agents of sleeping sickness, is thought to occur through an unusual, so far unidentified adenosine transporter. Saccharomyces cerevisiae was used in a functional screen to clone a gene (TbAT1) from Trypanosoma brucei brucei that encodes a nucleoside transporter. When expressed in yeast, TbAT1 enabled adenosine uptake and conferred susceptibility to melaminophenyl arsenicals. Drug-resistant trypanosomes harbor a defective TbAT1 variant. The molecular identification of the entry route of trypanocides opens the way to approaches for diagnosis and treatment of drug-resistant sleeping sickness.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maser, P -- Sutterlin, C -- Kralli, A -- Kaminsky, R -- New York, N.Y. -- Science. 1999 Jul 9;285(5425):242-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Tropical Institute, CH-4002 Basel, Switzerland. Biozentrum, University of Basel, CH-4056 Basel, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10398598" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine/*metabolism ; Amino Acid Sequence ; Animals ; Arsenicals/metabolism/pharmacology ; Biological Transport ; Carrier Proteins/chemistry/genetics/*metabolism ; Cloning, Molecular ; Drug Resistance/genetics ; Genes, Protozoan ; Membrane Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; Mutation ; Nucleoside Transport Proteins ; Nucleosides/metabolism ; Purines/metabolism/pharmacology ; Saccharomyces cerevisiae/genetics ; Substrate Specificity ; Trypanocidal Agents/metabolism/*pharmacology ; Trypanosoma brucei brucei/*drug effects/genetics/*metabolism ; Trypanosomiasis, African/drug therapy/parasitology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    A new class of anthelmintics effective against drug-resistant nematodes (2008)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2008-03-14
    Description: Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity to a point where multidrug resistance against the three major classes of anthelmintics--the benzimidazoles, imidazothiazoles and macrocyclic lactones--has become a global phenomenon in gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an anthelmintic with a new mode of action. Here we report the discovery of the amino-acetonitrile derivatives (AADs) as a new chemical class of synthetic anthelmintics and describe the development of drug candidates that are efficacious against various species of livestock-pathogenic nematodes. These drug candidates seem to have a novel mode of action involving a unique, nematode-specific clade of acetylcholine receptor subunits. The AADs are well tolerated and of low toxicity to mammals, and overcome existing resistances to the currently available anthelmintics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaminsky, Ronald -- Ducray, Pierre -- Jung, Martin -- Clover, Ralph -- Rufener, Lucien -- Bouvier, Jacques -- Weber, Sandra Schorderet -- Wenger, Andre -- Wieland-Berghausen, Susanne -- Goebel, Thomas -- Gauvry, Noelle -- Pautrat, Francois -- Skripsky, Thomas -- Froelich, Olivier -- Komoin-Oka, Clarisse -- Westlund, Bethany -- Sluder, Ann -- Maser, Pascal -- England -- Nature. 2008 Mar 13;452(7184):176-80. doi: 10.1038/nature06722.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Novartis Centre de Recherche Sante Animale, CH-1566 St Aubin (FR), Switzerland. ronald.kaminsky@novartis.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18337814" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Amino Acid Sequence ; Aminoacetonitrile/adverse effects/*analogs & ; derivatives/pharmacokinetics/*pharmacology ; Animals ; Anthelmintics/chemistry/*classification/pharmacokinetics/*pharmacology ; Caenorhabditis elegans/drug effects/genetics/metabolism ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism ; Cattle ; Cattle Diseases/drug therapy/parasitology ; *Drug Resistance/genetics ; Larva/drug effects/genetics ; Molecular Sequence Data ; Nematoda/*drug effects/genetics/physiology ; Parasitic Diseases, Animal/drug therapy/*parasitology ; Receptors, Nicotinic/chemistry/genetics/metabolism ; Sheep/parasitology ; Sheep Diseases/drug therapy/parasitology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
    Electronic Resource
    Electronic Resource
    Modeling the Influence of Heterogeneous Adsorbent Microstructure upon Adsorption Equilibria for Binary Mixtures (1994)
    s.l. : American Chemical Society
    Langmuir 10 (1994), S. 530-537 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00014a032
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  • 4
    Electronic Resource
    Electronic Resource
    A Direct Assessment of Mean-Field Methods of Determining Pore Size Distributions of Microporous Media from Adsorption Isotherm Data (1994)
    s.l. : American Chemical Society
    Langmuir 10 (1994), S. 1556-1565 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00017a039
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  • 5
    Electronic Resource
    Electronic Resource
    Physical adsorption in heterogeneous porous materials: an analytical study of a one-dimensional model (1993)
    s.l. : American Chemical Society
    Langmuir 9 (1993), S. 561-567 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00026a033
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  • 6
    Electronic Resource
    Electronic Resource
    Timing of eclosion in marine insects on Mediterranean shores – studies on Clunio mediterraneus, C. ponticus and Thalassomyia frauenfeldi (Diptera: Chironomidae) (1997)
    Springer
    Marine biology 129 (1997), S. 513-521 
    Details
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In three Clunio stocks, two from the Mediterranean Sea (Banyuls, Rovinj) and one from the Black Sea (Sosopol), an identical circasemilunar eclosion pattern in combination with a circadian eclosion time of day was evoked in breeding experiments under an artificial moonlight cycle (four nights of 0.3 lux every 30 d, 12 h light:12 h dark). The eclosion peaks occurred on days with artificial moonlight and approximately 2 weeks later, and with regard to the time of day between mid-night and lights-on. In spite of the weak tidal amplitudes on Mediterranean shores, extreme low water levels occur when a nocturnal low-water time coincides on days around full and new moon (spring-tide situation) with winds from land to sea. Field observations at Banyuls and Rovinj agree with the experimental results. In contrast to Clunio spp. adults (life span only a few hours), Thalassomyia frauenfeldi adults (life span up to several days in the laboratory) demonstrated an unsynchronized eclosion pattern in the experiments (no lunar concentration, wide diurnal eclosion gate). Although inhabiting the same intertidal area, T. frauenfeldi walking on exposed intertidal substrates can delay egg-deposition for days and can probably wait for favorable low water levels. The taxonomical status of European Clunio populations is reviewed; minute morphological distinctions are presented for C. mediterraneus in the otherwise morphologically uniform, but ecophysiologically differentiated genus.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002270050192
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  • 7
    Electronic Resource
    Electronic Resource
    The effect of salts on hydrolysis in supercritical and near-critical water: Reactivity and availability
    Amsterdam : Elsevier
    The @Journal of Supercritical Fluids 5 (1992), S. 163-168 
    Details
    ISSN: 0896-8446
    Keywords: hydrolysis ; kinetics ; salt effects ; solvent effects ; supercritical ; water
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0896-8446(92)90003-3
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  • 8
    Electronic Resource
    Electronic Resource
    Monte Carlo evaluation of ensemble averages involving particle number variations in dense fluid systems (1994)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 101 (1994), S. 4986-4994 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: A general formalism is presented for the calculation of thermodynamic properties via statistical ensembles augmented with nonphysical states. These augmented ensembles can be readily incorporated into Monte Carlo molecular simulation methods. Of particular interest is evaluation of thermodynamic properties by Monte Carlo applications which involve particle number variations. The augmented states can be constructed to facilitate Markov transitions between states with varying number of particles. This in turn can greatly increase the convergence rates of property averages, especially for high density systems. This benefit is analogous to chemical catalysis, which by introducing low activation energy reaction pathways increases reaction rate (i.e., convergence rate) without affecting the overall equilibrium. The utility of augmented ensembles is demonstrated through novel Monte Carlo implementations which are efficient regardless of system density of grand ensemble simulation and test particle activity evaluation. Applications to pure hard-sphere and 12-6 Lennard-Jones fluid systems are specifically considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.467421
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  • 9
    Electronic Resource
    Electronic Resource
    The influence of adsorbent microstructure upon adsorption equilibria: Investigations of a model system (1991)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 95 (1991), S. 2936-2948 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: We present a theoretical study of the influence of the microstructure of a porous adsorbent upon associated adsorption behavior. A model is developed which describes the interactions of adsorbed molecules with an adsorbent treated as a matrix of particles each of which is a continuum of interaction centers. The model leads to an analytic expression for the adsorbate-adsorbent particle potential which is an analog of the 9-3 potential model for adsorption on planar solid surfaces. To illustrate the utility of the approach, an application to methane adsorbed in a microporous silica gel is presented. Several adsorbent microstructures are investigated, including a variety of crystal lattices as well as structures derived from equilibrium configurations of hard spheres. Adsorption in these structures is studied through calculation of Henry's law constants and by using grand canonical Monte Carlo simulation to determine adsorption isotherms and the structure of adsorbed fluids. The results obtained are related to details of the adsorbent microstructure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.461781
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  • 10
    Electronic Resource
    Electronic Resource
    Adsorption of fluids in disordered porous media from integral equation theory (1993)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 99 (1993), S. 3003-3013 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: We consider the application of the integral equation theory developed by Madden and Glandt to a recently developed model of methane adsorbed in a silica xerogel. At higher temperatures, above the bulk fluid critical temperature, the theory yields very good predictions of the adsorbate–matrix and adsorbate–adsorbate distribution functions. At lower temperatures, where the attractive intermolecular forces play a more dominant role in determining the microstructure, the agreement between simulation and theory deteriorates somewhat. It also becomes increasingly difficult to obtain solutions of the integral equations at low temperatures. We have found that for this system and others where the matrix particles are much larger than the adsorbate particles the adsorbate–matrix and adsorbate–adsorbate correlation functions differ only slightly from those of an equilibrium mixture of matrix and adsorbate particles. We offer an explanation for this result on the basis of cancellation of diagrams in the cluster expansion of the total correlation function. We discuss the determination of adsorption isotherms from integral equation theory using expressions developed in the context of density functional theory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.465206
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