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  • 1
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    Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-11-19
    Description: Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of 〉4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration 〈 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473092/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3473092/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meister, Stephan -- Plouffe, David M -- Kuhen, Kelli L -- Bonamy, Ghislain M C -- Wu, Tao -- Barnes, S Whitney -- Bopp, Selina E -- Borboa, Rachel -- Bright, A Taylor -- Che, Jianwei -- Cohen, Steve -- Dharia, Neekesh V -- Gagaring, Kerstin -- Gettayacamin, Montip -- Gordon, Perry -- Groessl, Todd -- Kato, Nobutaka -- Lee, Marcus C S -- McNamara, Case W -- Fidock, David A -- Nagle, Advait -- Nam, Tae-gyu -- Richmond, Wendy -- Roland, Jason -- Rottmann, Matthias -- Zhou, Bin -- Froissard, Patrick -- Glynne, Richard J -- Mazier, Dominique -- Sattabongkot, Jetsumon -- Schultz, Peter G -- Tuntland, Tove -- Walker, John R -- Zhou, Yingyao -- Chatterjee, Arnab -- Diagana, Thierry T -- Winzeler, Elizabeth A -- R01 AI079709/AI/NIAID NIH HHS/ -- R01 AI079709-04/AI/NIAID NIH HHS/ -- R01 AI090141/AI/NIAID NIH HHS/ -- R01 AI090141-02/AI/NIAID NIH HHS/ -- R01AI090141/AI/NIAID NIH HHS/ -- WT078285/Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2011 Dec 9;334(6061):1372-7. doi: 10.1126/science.1211936. Epub 2011 Nov 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22096101" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Cell Line, Tumor ; *Drug Discovery ; Drug Evaluation, Preclinical ; Drug Resistance ; Erythrocytes/parasitology ; Humans ; Imidazoles/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Liver/*parasitology ; Malaria/*drug therapy/parasitology/prevention & control ; Mice ; Mice, Inbred BALB C ; Molecular Structure ; Piperazines/chemistry/pharmacokinetics/*pharmacology/therapeutic use ; Plasmodium/cytology/*drug effects/growth & development/physiology ; Plasmodium berghei/cytology/drug effects/growth & development/physiology ; Plasmodium falciparum/cytology/drug effects/growth & development/physiology ; Plasmodium yoelii/cytology/drug effects/growth & development/physiology ; Polymorphism, Single Nucleotide ; Protozoan Proteins/chemistry/genetics/metabolism ; Random Allocation ; Small Molecule Libraries ; Sporozoites/drug effects/growth & development
    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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    Epidemiology: resistance mapping in malaria (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-06-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bright, A Taylor -- Winzeler, Elizabeth A -- England -- Nature. 2013 Jun 27;498(7455):446-7. doi: 10.1038/498446b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine, University of California, San Diego, La Jolla, California 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23803843" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antimalarials/*pharmacology ; Artemisinins/pharmacology ; Drug Resistance/*drug effects/*genetics ; Genome, Protozoan/genetics ; Humans ; Malaria, Falciparum/epidemiology/*parasitology ; Plasmodium falciparum/*drug effects/*genetics/physiology
    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
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    A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-05-15
    Description: Clinical malaria is associated with the proliferation of Plasmodium parasites in human erythrocytes. The coordinated processes of parasite egress from and invasion into erythrocytes are rapid and tightly regulated. We have found that the plant-like calcium-dependent protein kinase PfCDPK5, which is expressed in invasive merozoite forms of Plasmodium falciparum, was critical for egress. Parasites deficient in PfCDPK5 arrested as mature schizonts with intact membranes, despite normal maturation of egress proteases and invasion ligands. Merozoites physically released from stalled schizonts were capable of invading new erythrocytes, separating the pathways of egress and invasion. The arrest was downstream of cyclic guanosine monophosphate-dependent protein kinase (PfPKG) function and independent of protease processing. Thus, PfCDPK5 plays an essential role during the blood stage of malaria replication.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109083/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109083/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dvorin, Jeffrey D -- Martyn, Derek C -- Patel, Saurabh D -- Grimley, Joshua S -- Collins, Christine R -- Hopp, Christine S -- Bright, A Taylor -- Westenberger, Scott -- Winzeler, Elizabeth -- Blackman, Michael J -- Baker, David A -- Wandless, Thomas J -- Duraisingh, Manoj T -- 086550/Wellcome Trust/United Kingdom -- G1000779/Medical Research Council/United Kingdom -- GM073046/GM/NIGMS NIH HHS/ -- K08 AI087874/AI/NIAID NIH HHS/ -- K12-HD000850/HD/NICHD NIH HHS/ -- MC_U117532063/Medical Research Council/United Kingdom -- R01 AI057919/AI/NIAID NIH HHS/ -- R01 AI057919-05/AI/NIAID NIH HHS/ -- R01 GM073046/GM/NIGMS NIH HHS/ -- R01AI057919/AI/NIAID NIH HHS/ -- U117532063/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2010 May 14;328(5980):910-2. doi: 10.1126/science.1188191.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20466936" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium-Binding Proteins/chemistry/genetics/*metabolism ; Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism ; Enzyme Inhibitors/pharmacology ; Erythrocytes/*parasitology ; Host-Parasite Interactions ; Humans ; Ligands ; Merozoites/enzymology/physiology ; Models, Biological ; Morpholines/metabolism ; Plasmodium falciparum/cytology/enzymology/growth & development/*physiology ; Protein Kinases/chemistry/genetics/*metabolism ; Protozoan Proteins/chemistry/genetics/*metabolism ; Pyridines/pharmacology ; Pyrroles/pharmacology ; Recombinant Fusion Proteins/chemistry/metabolism ; Schizonts/cytology/enzymology/physiology
    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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  • 4
    Electronic Resource
    Electronic Resource
    Formation of an organized monolayer by solution adsorption of octadecyltrichlorosilane on gold: electrochemical properties and structural characterization (1986)
    s.l. : American Chemical Society
    Langmuir 2 (1986), S. 239-244 
    Details
    ISSN: 1520-5827
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/la00068a022
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  • 5
    Electronic Resource
    Electronic Resource
    Meiofauna and the thiobios in the east flower garden brine seep (1983)
    Springer
    Marine biology 73 (1983), S. 269-283 
    Details
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Special hydrodynamic-chemical conditions at the East Flower Garden brine seep have provided the opportunity to examine the community structure of the thiobios and the oxybiotic-thiobiotic boundary. The boundary between the thiobios, whose population maxima occur in sulfidedependent chemoclines and which presumably have an ecologic requirement for sulfide, and the oxybios, which occur in oxidized zones above the chemocline, is controlled by sulfide, not oxygen. The boundary, which may not be at zero sulfide, is determined by a time-concentration phenomenon based on a dynamic interplay of sulfide and oxygen supply rates and the biota's sulfide detoxification capabilities. In Gollum's Canyon, where oxygen is plentiful, the boundary is at 10–40 μg-atoms·l-1 sulfide. Total abundances of organisms at thiobiotic stations were comparable to total abundances at oxybiotic stations. Highest thiobiotic abundance was 202 051 organisms per m2; highest oxybiotic abundance was 240 572 organisms per m2. The thiobios is dominated by representatives of the lower Bilateria (viz. Gnathostomulida, Platyhelminthes and Aschelminthes). These groups accounted for 50–80% of all the organisms present in the thiobiotic stations but less than 20% of all organisms in the oxybiotic stations. At two thiobiotic stations, over 50% of all organisms were gnathostomulids. Thiobios included macrofaunal as well as meiofaunal components. Peak abundances of amphipods were associated with the thiobiotic environment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00392253
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of turbidity on calcification rate, protein concentration and the free amino acid pool of the coral Acropora cervicornis (1985)
    Springer
    Marine biology 87 (1985), S. 33-46 
    Details
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Calcification rate in the coral Acropora cervicornis was reduced significantly when exposed for 24 h to 100-ppm kaolin, but was unchanged in corals exposed to 50-ppm kaolin. Calcification rate returned to control levels during a 48-h recovery period. Most free amino acids (FAA) in the FAA pool decreased significantly in corals exposed to 100-ppm kaolin, but were unchanged in corals exposed to 50-ppm kaolin. After a 48-h recovery period, the FAA pool remained considerably below control levels in the 100-ppm exposed corals and dropped below control levels in the 50-ppm exposed corals. Calcification rate dropped less and later during the exposure period in the growing tip than in sections further down the stalk. The reduction in FAA pool size was considerably larger in the growing tip than further down the stalk. Soluble protein concentration remained unchanged during both exposure and recovery. The data are consistent with the interpretation that turbidity not only causes a decrease in photosynthetic rate and the synthesis of small molecules, but also causes a large increase in the utilization of stored organic molecules for such metabolically costly processes as mucus production and sediment removal.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00397003
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  • 7
    Electronic Resource
    Electronic Resource
    Effects on Migration of Marine Organisms in the Gulf of Mexico (1970)
    [s.l.] : Nature Publishing Group
    Nature 226 (1970), S. 1155-1156 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE research vessel Alaminos from Texas A & M University was in the Gulf of Mexico on March 7 to record changes in the near-surface layers of sea and air as a consequence of the eclipse. So that a maximum variation in incident solar radiation could be realized, the observing site was chosen at ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/2261155a0
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  • 8
    Electronic Resource
    Electronic Resource
    Effect of Ethyl Alcohol and Carbon Dioxide on the Sporulation of Bakers' Yeast (1949)
    [s.l.] : Nature Publishing Group
    Nature 164 (1949), S. 544-544 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] THE sporulation of a strain of Saccharomyces cerevisiœ, carefully maintained true to type as a commercial baking yeast, has varied in 5–50 per cent of the cells under apparently the same conditions; namely, on slants of ‘Difco’ nutrient agar at pH 7.3 incubated for three days at 30° C. ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/164544a0
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  • 9
    Electronic Resource
    Electronic Resource
    The importance of monitoring metabolic recovery in the coral Acropora cervicornis after short-term exposure to drilling muds: Calcification rate and protein concentration (1984)
    Springer
    Coral reefs 2 (1984), S. 215-225 
    Details
    ISSN: 1432-0975
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract The effect of used drilling muds on coral health was examined by monitoring changes in calcification rate and soluble tissue protein concentration in the coral Acropora cervicornis. Exposure to 25 ppm (v/v) of one mud for 24 h reduced calcification rate in the growing tips by as much as 62%. In recovery experiments, corals were exposed to drilling muds for 24 h; some of them were allowed to recover in clean seawater for 48 h. After the 24-hour exposure, calcification rates were significantly less than those of the controls. After a 48-hour recovery period, calcification rates returned to control levels for one mud but were still significantly below control levels for another. The results indicate that the capacity for recovery after exposure cannot be predicted from the results of experiments on exposure only. Recovery capacity must be independently verified for all studies on the effects of short-term exposure to drilling muds.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00263575
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  • 10
    Electronic Resource
    Electronic Resource
    Effect of eight outer continental shelf drilling muds on the calcification rate and free amino acid pool of the coralAcropora cervicornis (1984)
    Springer
    Bulletin of environmental contamination and toxicology 33 (1984), S. 362-372 
    Details
    ISSN: 1432-0800
    Source: Springer Online Journal Archives 1860-2000
    Topics: Energy, Environment Protection, Nuclear Power Engineering , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01625556
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