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  • 1
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    Population Structure Shapes Copy Number Variation in Malaria Parasites (2016)
    Oxford University Press
    Details
    Publication Date: 2016-02-20
    Description: If copy number variants (CNVs) are predominantly deleterious, we would expect them to be more efficiently purged from populations with a large effective population size ( N e ) than from populations with a small N e . Malaria parasites ( Plasmodium falciparum ) provide an excellent organism to examine this prediction, because this protozoan shows a broad spectrum of population structures within a single species, with large, stable, outbred populations in Africa, small unstable inbred populations in South America and with intermediate population characteristics in South East Asia. We characterized 122 single-clone parasites, without prior laboratory culture, from malaria-infected patients in seven countries in Africa, South East Asia and South America using a high-density single-nucleotide polymorphism/CNV microarray. We scored 134 high-confidence CNVs across the parasite exome, including 33 deletions and 102 amplifications, which ranged in size from 〈500 bp to 59 kb, as well as 10,107 flanking, biallelic single-nucleotide polymorphisms. Overall, CNVs were rare, small, and skewed toward low frequency variants, consistent with the deleterious model. Relative to African and South East Asian populations, CNVs were significantly more common in South America, showed significantly less skew in allele frequencies, and were significantly larger. On this background of low frequency CNV, we also identified several high-frequency CNVs under putative positive selection using an F ST outlier analysis. These included known adaptive CNVs containing rh2b and pfmdr1 , and several other CNVs (e.g., DNA helicase and three conserved proteins) that require further investigation. Our data are consistent with a significant impact of genetic structure on CNV burden in an important human pathogen.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    Resolution of Brassicaceae Phylogeny Using Nuclear Genes Uncovers Nested Radiations and Supports Convergent Morphological Evolution (2016)
    Oxford University Press
    Details
    Publication Date: 2016-01-24
    Description: Brassicaceae is one of the most diverse and economically valuable angiosperm families with widely cultivated vegetable crops and scientifically important model plants, such as Arabidopsis thaliana . The evolutionary history, ecological, morphological, and genetic diversity, and abundant resources and knowledge of Brassicaceae make it an excellent model family for evolutionary studies. Recent phylogenetic analyses of the family revealed three major lineages (I, II, and III), but relationships among and within these lineages remain largely unclear. Here, we present a highly supported phylogeny with six major clades using nuclear markers from newly sequenced transcriptomes of 32 Brassicaceae species and large data sets from additional taxa for a total of 55 species spanning 29 out of 51 tribes. Clade A consisting of Lineage I and Macropodium nivale is sister to combined Clade B (with Lineage II and others) and a new Clade C. The ABC clade is sister to Clade D with species previously weakly associated with Lineage II and Clade E (Lineage III) is sister to the ABCD clade. Clade F (the tribe Aethionemeae) is sister to the remainder of the entire family. Molecular clock estimation reveals an early radiation of major clades near or shortly after the Eocene–Oligocene boundary and subsequent nested divergences of several tribes of the previously polytomous Expanded Lineage II. Reconstruction of ancestral morphological states during the Brassicaceae evolution indicates prevalent parallel (convergent) evolution of several traits over deep times across the entire family. These results form a foundation for future evolutionary analyses of structures and functions across Brassicaceae.
    Print ISSN: 0737-4038
    Electronic ISSN: 1537-1719
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase (1990)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1990-01-12
    Description: The murine white spotting locus (W) is allelic with the proto-oncogene c-kit, which encodes a transmembrane tyrosine protein kinase receptor for an unknown ligand. Mutations at the W locus affect various aspects of hematopoiesis and the proliferation and migration of primordial germ cells and melanoblasts during development to varying degrees of severity. The W42 mutation has a particularly severe effect in both the homozygous and the heterozygous states. The molecular basis of the W42 mutation was determined. The c-kit protein products in homozygous mutant mast cells were expressed normally but displayed a defective tyrosine kinase activity in vitro. Nucleotide sequence analysis of mutant complementary DNAs revealed a missense mutation that replaces aspartic acid with asparagine at position 790 in the c-kit protein product. Aspartic acid-790 is a conserved residue in all protein kinases. These results provide an explanation for the dominant nature of the W42 mutation and provide insight into the mechanism of c-kit-mediated signal transduction.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, J C -- Nocka, K -- Ray, P -- Traktman, P -- Besmer, P -- P01-CA-16599/CA/NCI NIH HHS/ -- R01-CA-32926/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1990 Jan 12;247(4939):209-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Program, Sloan Kettering Institute, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1688471" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cells, Cultured ; DNA/genetics ; Gene Expression ; Homozygote ; Liver/analysis/cytology/embryology ; Mast Cells/metabolism ; Mice ; Molecular Sequence Data ; *Mutation ; *Phenotype ; Polymerase Chain Reaction ; Protein-Tyrosine Kinases/*genetics ; Proto-Oncogene Proteins/*genetics ; Proto-Oncogene Proteins c-kit ; RNA/analysis ; Receptors, Cell Surface/genetics ; Signal Transduction
    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
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    A major genome region underlying artemisinin resistance in malaria (2012)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2012-04-12
    Description: Evolving resistance to artemisinin-based compounds threatens to derail attempts to control malaria. Resistance has been confirmed in western Cambodia and has recently emerged in western Thailand, but is absent from neighboring Laos. Artemisinin resistance results in reduced parasite clearance rates (CRs) after treatment. We used a two-phase strategy to identify genome region(s) underlying this ongoing selective event. Geographical differentiation and haplotype structure at 6969 polymorphic single-nucleotide polymorphisms (SNPs) in 91 parasites from Cambodia, Thailand, and Laos identified 33 genome regions under strong selection. We screened SNPs and microsatellites within these regions in 715 parasites from Thailand, identifying a selective sweep on chromosome 13 that shows strong association (P = 10(-6) to 10(-12)) with slow CRs, illustrating the efficacy of targeted association for identifying the genetic basis of adaptive traits.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355473/" 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/PMC3355473/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheeseman, Ian H -- Miller, Becky A -- Nair, Shalini -- Nkhoma, Standwell -- Tan, Asako -- Tan, John C -- Al Saai, Salma -- Phyo, Aung Pyae -- Moo, Carit Ler -- Lwin, Khin Maung -- McGready, Rose -- Ashley, Elizabeth -- Imwong, Mallika -- Stepniewska, Kasia -- Yi, Poravuth -- Dondorp, Arjen M -- Mayxay, Mayfong -- Newton, Paul N -- White, Nicholas J -- Nosten, Francois -- Ferdig, Michael T -- Anderson, Timothy J C -- 089275/Wellcome Trust/United Kingdom -- 093956/Wellcome Trust/United Kingdom -- AI075145/AI/NIAID NIH HHS/ -- C06 RR013556/RR/NCRR NIH HHS/ -- R01 AI048071/AI/NIAID NIH HHS/ -- R01 AI075145/AI/NIAID NIH HHS/ -- R37 AI048071/AI/NIAID NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2012 Apr 6;336(6077):79-82. doi: 10.1126/science.1215966.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Texas Biomedical Research Institute, San Antonio, TX 78245, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491853" target="_blank"〉PubMed〈/a〉
    Keywords: Antimalarials/*pharmacology/therapeutic use ; Artemisinins/*pharmacology/therapeutic use ; Cambodia ; DNA Copy Number Variations ; Drug Resistance/*genetics ; Gene Frequency ; Genetic Association Studies ; *Genome, Protozoan ; Haplotypes ; Humans ; Laos ; Malaria, Falciparum/drug therapy/*parasitology ; Microsatellite Repeats ; Plasmodium falciparum/*drug effects/*genetics ; Polymorphism, Single Nucleotide ; Protozoan Proteins/genetics ; *Selection, Genetic ; Thailand
    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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  • 5
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    Astrophysics: A dark cloud unveils its secrets (2013)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2013-08-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tan, Jonathan C -- England -- Nature. 2013 Aug 29;500(7464):537-8. doi: 10.1038/500537a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23985868" target="_blank"〉PubMed〈/a〉
    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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  • 6
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    Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing (2012)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2012-06-23
    Description: Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P. falciparum genome.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738909/" 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/PMC3738909/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manske, Magnus -- Miotto, Olivo -- Campino, Susana -- Auburn, Sarah -- Almagro-Garcia, Jacob -- Maslen, Gareth -- O'Brien, Jack -- Djimde, Abdoulaye -- Doumbo, Ogobara -- Zongo, Issaka -- Ouedraogo, Jean-Bosco -- Michon, Pascal -- Mueller, Ivo -- Siba, Peter -- Nzila, Alexis -- Borrmann, Steffen -- Kiara, Steven M -- Marsh, Kevin -- Jiang, Hongying -- Su, Xin-Zhuan -- Amaratunga, Chanaki -- Fairhurst, Rick -- Socheat, Duong -- Nosten, Francois -- Imwong, Mallika -- White, Nicholas J -- Sanders, Mandy -- Anastasi, Elisa -- Alcock, Dan -- Drury, Eleanor -- Oyola, Samuel -- Quail, Michael A -- Turner, Daniel J -- Ruano-Rubio, Valentin -- Jyothi, Dushyanth -- Amenga-Etego, Lucas -- Hubbart, Christina -- Jeffreys, Anna -- Rowlands, Kate -- Sutherland, Colin -- Roper, Cally -- Mangano, Valentina -- Modiano, David -- Tan, John C -- Ferdig, Michael T -- Amambua-Ngwa, Alfred -- Conway, David J -- Takala-Harrison, Shannon -- Plowe, Christopher V -- Rayner, Julian C -- Rockett, Kirk A -- Clark, Taane G -- Newbold, Chris I -- Berriman, Matthew -- MacInnis, Bronwyn -- Kwiatkowski, Dominic P -- 075491/Z/04/Wellcome Trust/United Kingdom -- 077012/Z/05/Z/Wellcome Trust/United Kingdom -- 082370/Wellcome Trust/United Kingdom -- 089275/Wellcome Trust/United Kingdom -- 090532/Wellcome Trust/United Kingdom -- 090532/Z/09/Z/Wellcome Trust/United Kingdom -- 090770/Wellcome Trust/United Kingdom -- 090770/Z/09/Z/Wellcome Trust/United Kingdom -- 092654/Wellcome Trust/United Kingdom -- 093956/Wellcome Trust/United Kingdom -- 098051/Wellcome Trust/United Kingdom -- 55005502/Howard Hughes Medical Institute/ -- G0600718/Medical Research Council/United Kingdom -- G19/9/Medical Research Council/United Kingdom -- Intramural NIH HHS/ -- England -- Nature. 2012 Jul 19;487(7407):375-9. doi: 10.1038/nature11174.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22722859" target="_blank"〉PubMed〈/a〉
    Keywords: Alleles ; *Biodiversity ; Genome, Protozoan ; Genotype ; *High-Throughput Nucleotide Sequencing ; Humans ; Malaria, Falciparum/*parasitology ; Phylogeny ; Plasmodium falciparum/classification/*genetics ; Polymorphism, Single Nucleotide ; Principal Component Analysis
    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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  • 7
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    Hydrodealkenylative C(sp3)-C(sp2) bond fragmentation (2019)
    American Association for the Advancement of Science (AAAS)
    In: Science
    Details
    Publication Date: 2019
    Description: 〈p〉Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity—particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp〈sup〉3〈/sup〉)–C(sp〈sup〉2〈/sup〉) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.〈/p〉
    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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  • 8
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    Chemical structure, network topology, and porosity effects on the mechanical properties of Zeolitic Imidazolate Frameworks (2010)
    National Academy of Sciences
    Details
    Publication Date: 2010-05-17
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 9
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    Millimetre-wave and near-infrared signposts of massive molecular clump evolution and star cluster formation (2013)
    Oxford University Press
    Details
    Publication Date: 2013-06-09
    Description: We report new near-infrared and mm-wave observational data on a selection of massive Galactic molecular clumps (part of the Census of High- and Medium-mass Protostars sample) and their associated young star clusters. The clumps show, for the first time in a ‘dense gas tracer’, a significant correlation between HCO + line emission from cold molecular gas and Br line emission of associated nebulae. This correlation arises in the HCO + line's brightness, not its linewidth. In contrast, the correlation between the N 2 H + line emission and Br is weak or absent. The HCO + /N 2 H + line ratio also varies widely from clump to clump: bright HCO + emission tends to be more closely associated with Br nebulosity, while bright N 2 H + emission tends to avoid areas that are bright in Br. Both molecular species show correlations of weak significance with infrared H 2 v  = 1 -〉 0 and v  = 2 -〉 1 line emission, in or near the clumps. The H 2 emission line ratio is consistent with fluorescent excitation in most of the clumps, although thermal excitation is seen in a few clumps. We interpret these trends as evidence for evolution in the gas conditions due to the effects of ongoing star formation in the clumps, in particular, the importance of UV radiation from massive Young Stellar Objects as the driving agent that heats the molecular gas and alters its chemistry. This suggests that some traditional dense gas tracers of molecular clouds do not sample a homogeneous population of clumps, i.e. that the HCO + brightness in particular is directly related to the heating and disruption of cold gas by massive young stars, whereas the N 2 H + better samples gas not yet affected by this process. We therefore suggest that the HCO + –N 2 H + –Br relationship is a useful diagnostic of a molecular clump's progress in forming massive stars.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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  • 10
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    Widespread deuteration across the IRDC G035.39-00.33 (2016)
    Oxford University Press
    Details
    Publication Date: 2016-03-23
    Description: Infrared Dark Clouds (IRDCs) are cold, dense regions that are usually found within Giant Molecular Clouds. Ongoing star formation within IRDCs is typically still deeply embedded within the surrounding molecular gas. Characterizing the properties of relatively quiescent IRDCs may therefore help us to understand the earliest phases of the star formation process. Studies of local molecular clouds have revealed that deuterated species are enhanced in the earliest phases of star formation. In this paper, we test this towards IRDC G035.39–00.33. We present an 80 arcsec by 140 arcsec map of the J = 2 -〉 1 transition of N 2 D + , obtained with the Institut de Radioastronomie Millimétrique 30 m telescope telescope. We find that N 2 D + is widespread throughout G035.39–00.33. Complementary observations of N 2 H + (1 – 0) are used to estimate the deuterium fraction, D $_\mathrm{frac}^\mathrm{N_2H^+}$    N (N 2 D + )/ N (N 2 H + ). We report a mean D $_\mathrm{frac}^\mathrm{N_2H^+}$  = 0.04 ± 0.01, with a maximum of D $_\mathrm{frac}^\mathrm{N_2H^+}$  = 0.09 ± 0.02. The mean deuterium fraction is ~3 orders of magnitude greater than the interstellar [D]/[H] ratio. High angular resolution observations are required to exclude beam dilution effects of compact deuterated cores. Using chemical modelling, we find that the average observed values of D $_\mathrm{frac}^\mathrm{N_2H^+}$ are in agreement with an equilibrium deuterium fraction, given the general properties of the cloud. This implies that the IRDC is at least ~3 Myr old, which is ~8 times longer than the mean free-fall time of the observed deuterated region.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
    Published by Oxford University Press
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