88 research outputs found
Origin and evolution of the octoploid strawberry genome.
Cultivated strawberry emerged from the hybridization of two wild octoploid species, both descendants from the merger of four diploid progenitor species into a single nucleus more than 1 million years ago. Here we report a near-complete chromosome-scale assembly for cultivated octoploid strawberry (Fragaria × ananassa) and uncovered the origin and evolutionary processes that shaped this complex allopolyploid. We identified the extant relatives of each diploid progenitor species and provide support for the North American origin of octoploid strawberry. We examined the dynamics among the four subgenomes in octoploid strawberry and uncovered the presence of a single dominant subgenome with significantly greater gene content, gene expression abundance, and biased exchanges between homoeologous chromosomes, as compared with the other subgenomes. Pathway analysis showed that certain metabolomic and disease-resistance traits are largely controlled by the dominant subgenome. These findings and the reference genome should serve as a powerful platform for future evolutionary studies and enable molecular breeding in strawberry
In vitro production of cat-restricted Toxoplasma pre-sexual stages
Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. ), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission
Protection from the 2009 H1N1 Pandemic Influenza by an Antibody from Combinatorial Survivor-Based Libraries
Influenza viruses elude immune responses and antiviral chemotherapeutics through genetic drift and reassortment. As a result, the development of new strategies that attack a highly conserved viral function to prevent and/or treat influenza infection is being pursued. Such novel broadly acting antiviral therapies would be less susceptible to virus escape and provide a long lasting solution to the evolving virus challenge. Here we report the in vitro and in vivo activity of a human monoclonal antibody (A06) against two isolates of the 2009 H1N1 pandemic influenza virus. This antibody, which was obtained from a combinatorial library derived from a survivor of highly pathogenic H5N1 infection, neutralizes H5N1, seasonal H1N1 and 2009 “Swine” H1N1 pandemic influenza in vitro with similar potency and is capable of preventing and treating 2009 H1N1 influenza infection in murine models of disease. These results demonstrate broad activity of the A06 antibody and its utility as an anti-influenza treatment option, even against newly evolved influenza strains to which there is limited immunity in the general population
Viroplasm and large virus-like particles in the dinoflagellate Gymnodinium uberrimum
Virus-like particles (VLPs) measuring 385±5 nm in diameter are described in the freshwater dinoflagellate Gymnodinium uberrimum . The VLPs are found in association with, and “budding” from a vesicular viroplasmic area. A similar viroplasm was also found in a chrysophycean alga, Mallomonas sp. collected from the same general area in Saginaw Bay of Lake Huron. The nature of these VLPs and their virogenic stroma, in these algae from the Laurentian Great Lakes are discussed in the present report.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41733/1/709_2005_Article_BF01275735.pd
Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions
Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 x 10(-9)) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 x 10(-9)) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.Peer reviewe
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CP-5 Reactor yard characterization study
This paper presents the results of a characterization study of the yard of the CP-5 Reactor at Argonne National Laboratory, Argonne, Illinois. Low-level radiological contamination is suspected to have occurred at the yard primarily because of leaks from the cooling tower located in the yard. The CP-5 Reactor was a 5-MW research reactor that operated from 1954 until its shutdown in 1979. The CP-5 yard also stored a number of pieces of scientific equipment that exhibited measurable amounts of radioactivity. The reactor and associated yard area are in the process of being decommissioned. As a preliminary step in this direction, a single exploratory monitoring well was installed in the yard. Levels of hydrogen-3 (tritium) ranged from 6.5 to 15.9 nCi/L, and the level of strontium-90 in groundwater ranged from 1.23 to 3.32 pCi/L. Preliminary characterization included drilling two additional monitoring wells and several soil borings in order to collect sufficient soil and groundwater samples. Samples were analyzed for organic, inorganic, and radiological parameters. Low analytical sensitivity for tritium was emphasized for this project. The RESRAD code was used to convert the radiological results of soil samples into human dosage equivalents
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