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  • 1
    Publication Date: 2012-05-30
    Description: Human malaria infection begins with a one-time asymptomatic liver stage followed by a cyclic symptomatic blood stage. All high-throughput malaria drug discovery efforts have focused on the cyclic blood stage, which has limited potential for the prophylaxis, transmission blocking, and eradication efforts that will be needed in the future. To address these unmet needs, a high-throughput phenotypic liver-stage Plasmodium parasite screen was developed to systematically identify molecules with liver-stage efficacy. The screen recapitulates liver-stage infection by isolating luciferase-expressing Plasmodium berghei parasites directly from the salivary glands of infected mosquitoes, adding them to confluent human liver cells in 384-well plates, and measuring luciferase activity after a suitable incubation period. Screening 5,375 known bioactive compounds identified 37 liver-stage malaria inhibitors with diverse modes of action, as shown by inhibition time course experiments. Further analysis of the hits in the Food and Drug Administration-approved drug subset revealed compounds that seem to act specifically on the liver stage of infection, suggesting that this phase of the parasite’s life cycle presents a promising area for new drug discovery. Notably, many active compounds in this screen have molecular structures and putative targets distinctly different from those of known antimalarial agents.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2001-01-06
    Description: Intracellular bacteria and parasites typically invade host cells through the formation of an internalization vacuole around the invading pathogen. Plasmodium sporozoites, the infective stage of the malaria parasite transmitted by mosquitoes, have an alternative mechanism to enter cells. We observed breaching of the plasma membrane of the host cell followed by rapid repair. This mode of entry did not result in the formation of a vacuole around the sporozoite, and was followed by exit of the parasite from the host cell. Sporozoites traversed the cytosol of several cells before invading a hepatocyte by formation of a parasitophorous vacuole, in which they developed into the next infective stage. Sporozoite migration through several cells in the mammalian host appears to be essential for the completion of the life cycle.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mota, M M -- Pradel, G -- Vanderberg, J P -- Hafalla, J C -- Frevert, U -- Nussenzweig, R S -- Nussenzweig, V -- Rodriguez, A -- New York, N.Y. -- Science. 2001 Jan 5;291(5501):141-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, New York University School of Medicine, 341 East 25 Street, New York, NY 10010, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11141568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cell Membrane/parasitology/physiology/ultrastructure ; Cell Movement ; Cytosol/metabolism/parasitology ; Dextrans/metabolism ; Endocytosis ; Flow Cytometry ; Fluorescein-5-isothiocyanate/*analogs & derivatives/metabolism ; Hepatocytes/*parasitology/ultrastructure ; Malaria/parasitology ; Mice ; Mice, Inbred BALB C ; Plasmodium/physiology ; Plasmodium yoelii/growth & development/*physiology ; Propidium/metabolism ; Toxoplasma/physiology ; Tumor Cells, Cultured ; Vacuoles/parasitology/ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-02-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waters, A P -- Mota, M M -- van Dijk, M R -- Janse, C J -- New York, N.Y. -- Science. 2005 Jan 28;307(5709):528-30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Parasitology, Leiden University Medical Centre, Leiden 2300 RC, Netherlands. a.p.waters @lumc.nl〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15681372" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Genes, Protozoan ; Genetic Engineering ; Hepatocytes/parasitology/physiology ; Humans ; Immunization Schedule ; Immunization, Secondary ; Malaria/*immunology/prevention & control ; *Malaria Vaccines/immunology ; Malaria, Falciparum/immunology/prevention & control ; Mice ; Plasmodium berghei/genetics/growth & development/*immunology ; Plasmodium falciparum/genetics/immunology ; Protozoan Proteins/genetics/physiology ; Sporozoites/genetics/growth & development/*immunology ; Vaccination ; Vaccines, Attenuated/immunology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2013-07-24
    Description: Residence within a customized vacuole is a highly successful strategy used by diverse intracellular microorganisms. The parasitophorous vacuole membrane (PVM) is the critical interface between Plasmodium parasites and their possibly hostile, yet ultimately sustaining, host cell environment. We show that torins, developed as ATP-competitive mammalian target of rapamycin (mTOR) kinase...
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 298 (1979), S. 136-139 
    ISSN: 1618-2650
    Keywords: Best. von Cadmium in Wasser ; Polarographie ; automat. Konzentrierung, 10−10 M
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary To simplify the determination of dissolved Cd(II) in water and sea water-like solutions at the 10−10–10−9 M level an automated concentration step was developed consisting of percolating about 21 of sample over a column with an immobilized reagent (ED3A) and dissolving the trapped cadmium in 0.1 M nitric acid. A concentration factor of 50 or more is easily obtained. Recoveries are about 90%. With anodic stripping differential pulse polarography as a final determination technique overall standard deviations are in the range of 0.1–0.4·10−10 Mol of Cd.
    Notes: Zusammenfassung Die Bestimmung von gelöstem Cd(II) in Wasser und Meereswasser ähnlichen Lösungen mit einem Gehalt von 10−10–10−9 M wurde durch eine automatisierte Konzentrierung vereinfacht, indem man etwa 2 1 Probe über eine Säule mit einem immobilisierten Reagens (ED3A) perkoliert und das gespeicherte Cd wieder in 0.1 M Salpetersäure löst. Ein Konzentrierungsfaktor von 50 oder mehr läßt sich leicht erreichen. Die Wiederfindungsraten waren etwa 90%. Mit ASDP-Polarographie als Endbestimmung wurden Gesamt-Standardabweichungen im Bereich von 0,1–0,4 · 10−10 Mol Cd gefunden.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 296 (1979), S. 345-349 
    ISSN: 1618-2650
    Keywords: Best. von Kupfer, Blei, Zink ; Spektralphotometrie, Atomabsorption ; Flamme, chromatogr. Trennung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary The sample of seawater (51) is freed from solid particles, buffered at pH 5.6 and percolated through a column filled with ED3A. After sample passage 15 ml 1 M hydrochloric acid solution are pumped through the column to dissolve the concentrated ions. The final measurement using flame atomic absorption is carried out in the hydrochloric acid solution. The total labour time is less than 15 min. The standard deviations (4 analyses) for the determination of Cu, Pb and Zn (in the normal concentration range of 2–6 μg · l−1) were 2–5%, 5% and 1–10%, the recoveries 100%, 102% and 104%, respectively. A concentration coefficient of 300–500 was obtained.
    Notes: Zusammenfassung Die Probe Meereswasser (51) wird nach Entfernen der festen Teilchen auf einen pH-Wert von 5,6 gepuffert und durch eine Trennsäule mit ED3A geführt. Die angereicherten Metallionen werden mit 15 ml 1 M HCl-Lösung eluiert. Anschließend erfolgt die Bestimmung durch Flammenatomabsorption. Die Methode erfordert insgesamt weniger als 15 min Arbeitszeit. Die Standardabweichungen (4 Best.) betragen für Cu, Pb und Zn (im normalen Bereich von etwa 2–6 μg·l−1) etwa 2–5%, 5% und 1–10%, die Wiederfindungsraten 100%, 102% bzw. 104%. Der Konzentrationskoeffizient beträgt 300 bis 500.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 304 (1980), S. 1-5 
    ISSN: 1618-2650
    Keywords: Chromatographie, Ionenaustausch ; Modellbildung, Messungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary A description of the way of obtaining the necessary experimental information for modelling an ion-exclusion column (polystyrene/sulphonic acid resin in the H+-form; elution of HCl) is given together with its results. A model for the detection system is obtained.
    Notes: Zusammenfassung Eine Methode wird beschrieben, die die notwendigen experimentellen Daten zur Modellbildung einer Ionen-Exklusions-Säule (Polystyrol/ Sulfonsäure-Harz in der H+-Form; Eluierung von HCl) liefert. Die Ergebnisse werden angegeben. Ein Modell der Detektion wurde aufgestellt.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 304 (1980), S. 104-110 
    ISSN: 1618-2650
    Keywords: Chromatographie, Ionenaustausch ; zwei math. Modelle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary Two attempts to set a mathematical model of an ion-exclusion column process (sulphonic acid ionexchange resin in the H+-form; HCl in the eluent) are described. The outcome of an experimental approach using curve fitting procedures has a similarity with the outcome of an approach departing from physical reasoning.
    Notes: Zusammenfassung Zwei Versuche zur Aufstellung eines mathematischen Modells für einen Ionen-Exklusions-Prozeß (Sulfonsäure-Ionenaustauschharz in der H+-Form; HCl im Eluens) werden beschrieben. Das Resultat einer experimentellen Methode (curvefitting) gleicht annähernd demjenigen, das mit physikalischen Überlegungen ermittelt wurde.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 285 (1977), S. 238-241 
    ISSN: 1618-2650
    Keywords: Best. von Zuckern, organ. Säuren in Lebensmitteln ; Chromatographie, Gas ; automatisches Aufarbeitungsverfahren
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary In the gas-chromatographic analysis of sugars and acids in foodstuffs, isolation and purification of the two types of components is time-consuming and laborious. An automated clean-up procedure, based on ion-exchange, has therefore been developed. A liquid food sample is successively percolated over a cation and anion and a cation exchanger. Sugars and acids are collected under the second and third column, respectively. A time programmer operates a set of pumps and a pneumatic valve system enabling simultaneous regeneration of columns not being eluted. Hence, handling of samples is continuous; each clean-up cycle takes 50 min.
    Notes: Zusammenfassung Eine flüssige Nahrungsmittelprobe wird nacheinander über einen Kationen-, einen Anionen- und einen Kationenaustauscher perkoliert. Die Zucker und die Säuren werden abgetrennt und im Eluat der zweiten bzw. dritten Austauschersäule gefunden. Ein Steuergerät schaltet auf Zeitbasis eine Gruppe von Pumpen und ein System mit pneumatischen Hähnen derart, daß in einem Cyclus (50 min) die Substanzen eluiert und die Säulen regeneriert werden. Anschließend werden die Proben verarbeitet. Einige Ergebnisse verschiedener Nahrungsmittel werden angeführt.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Fresenius' Zeitschrift für analytische Chemie 287 (1977), S. 19-22 
    ISSN: 1618-2650
    Keywords: Abtrennung von Kupfer(II) aus Wasser ; Säulenverfahren ; Ionenaustauscher, Oxin, AAS-Bestimmung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Summary A comparison is made between two automated column procedures for the separation and preconcentration of Cu(II) from natural waters. The column materials were: an anion-exchange resin and 8-hydroxyquinoline immobilized on a glass support. 8-Hydroxyquinoline showed about the same performance as the ion exchange resin, but was less time and labour consuming. Cu(II) determinations at the ppb level were checked with standard additions and the results were moreover compared with those obtained by another method.
    Notes: Zusammenfassung Zwei automatisierte Trennsäulensysteme zur Abtrennung und Anreicherung von Kupfer(II) aus natürlichen Wässern wurden verglichen. Das aktive Material war ein Anionaustauscher und 8Hydroxychinolin auf Glas. 8-Hydroxychinolin zeigte etwa dieselben Ergebnisse wie der Anionaustauscher, benötigte aber weniger Arbeits- und Zeitaufwand. Cu(II)-Bestimmungen im ppb-Bereich wurden nach dem Verfahren der Standardzugabe geprüft und die Ergebnisse mit denen einer anderen Methode verglichen.
    Type of Medium: Electronic Resource
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