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  • 1
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 8 ( 2019-02-19), p. 3262-3267
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 8 ( 2019-02-19), p. 3262-3267
    Abstract: Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 34 ( 2015-08-25), p. 10798-10803
    Abstract: Acute hepatopancreatic necrosis disease (AHPND) is a severe, newly emergent penaeid shrimp disease caused by Vibrio parahaemolyticus that has already led to tremendous losses in the cultured shrimp industry. Until now, its disease-causing mechanism has remained unclear. Here we show that an AHPND-causing strain of V. parahaemolyticus contains a 70-kbp plasmid (pVA1) with a postsegregational killing system, and that the ability to cause disease is abolished by the natural absence or experimental deletion of the plasmid-encoded homologs of the Photorhabdus insect-related (Pir) toxins PirA and PirB. We determined the crystal structure of the V. parahaemolyticus PirA and PirB (PirA vp and PirB vp ) proteins and found that the overall structural topology of PirA vp /PirB vp is very similar to that of the Bacillus Cry insecticidal toxin-like proteins, despite the low sequence identity ( 〈 10%). This structural similarity suggests that the putative PirAB vp heterodimer might emulate the functional domains of the Cry protein, and in particular its pore-forming activity. The gene organization of pVA1 further suggested that pirAB vp may be lost or acquired by horizontal gene transfer via transposition or homologous recombination.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
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  • 3
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 118, No. 6 ( 2021-02-09)
    Abstract: As all- trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority ( P 〈 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups ( P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5] , P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy ( https://www.clinicaltrials.gov/ , NCT01987297).
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2021
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 119, No. 46 ( 2022-11-15)
    Abstract: Defense against ultraviolet (UV) radiation exposure is essential for survival, especially in high-elevation species. Although some specific genes involved in UV response have been reported, the full view of UV defense mechanisms remains largely unexplored. Herein, we used integrated approaches to analyze UV responses in the highest-elevation frog, Nanorana parkeri . We show less damage and more efficient antioxidant activity in skin of this frog than those of its lower-elevation relatives after UV exposure. We also reveal genes related to UV defense and a corresponding temporal expression pattern in N. parkeri . Genomic and metabolomic analysis along with large-scale transcriptomic profiling revealed a time-dependent coordinated defense mechanism in N. parkeri . We also identified several microRNAs that play important regulatory roles, especially in decreasing the expression levels of cell cycle genes. Moreover, multiple defense genes (i.e., TYR for melanogenesis) exhibit positive selection with function-enhancing substitutions. Thus, both expression shifts and gene mutations contribute to UV adaptation in N. parkeri . Our work demonstrates a genetic framework for evolution of UV defense in a natural environment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 46 ( 2014-11-18)
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 46 ( 2014-11-18)
    Abstract: Comparative genomic analyses among closely related species can greatly enhance our understanding of plant gene and genome evolution. We report de novo-assembled AA-genome sequences for Oryza nivara , Oryza glaberrima , Oryza barthii , Oryza glumaepatula , and Oryza meridionalis . Our analyses reveal massive levels of genomic structural variation, including segmental duplication and rapid gene family turnover, with particularly high instability in defense-related genes. We show, on a genomic scale, how lineage-specific expansion or contraction of gene families has led to their morphological and reproductive diversification, thus enlightening the evolutionary process of speciation and adaptation. Despite strong purifying selective pressures on most Oryza genes, we documented a large number of positively selected genes, especially those genes involved in flower development, reproduction, and resistance-related processes. These diversifying genes are expected to have played key roles in adaptations to their ecological niches in Asia, South America, Africa and Australia. Extensive variation in noncoding RNA gene numbers, function enrichment, and rates of sequence divergence might also help account for the different genetic adaptations of these rice species. Collectively, these resources provide new opportunities for evolutionary genomics, numerous insights into recent speciation, a valuable database of functional variation for crop improvement, and tools for efficient conservation of wild rice germplasm.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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  • 6
    Online Resource
    Online Resource
    Association for Computing Machinery (ACM) ; 2011
    In:  ACM Transactions on Asian Language Information Processing Vol. 10, No. 3 ( 2011-09), p. 1-20
    In: ACM Transactions on Asian Language Information Processing, Association for Computing Machinery (ACM), Vol. 10, No. 3 ( 2011-09), p. 1-20
    Abstract: We introduce a method for learning to translate out-of-vocabulary (OOV) words. The method focuses on combining sublexical/constituent translations of an OOV to generate its translation candidates. In our approach, wildcard searches are formulated based on our OOV analysis, aimed at maximizing the probability of retrieving OOVs’ sublexical translations from existing resources of Machine Translation (MT) systems. At run-time, translation candidates of the unknown words are generated from their suitable sublexical translations and ranked based on monolingual and bilingual information. We have incorporated the OOV model into a state-of-the-art machine translation system and experimental results show that our model indeed helps to ease the impact of OOVs on translation quality, especially for sentences containing more OOVs (significant improvement).
    Type of Medium: Online Resource
    ISSN: 1530-0226 , 1558-3430
    Language: English
    Publisher: Association for Computing Machinery (ACM)
    Publication Date: 2011
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  • 7
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2002
    In:  Science Vol. 296, No. 5565 ( 2002-04-05), p. 79-92
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 296, No. 5565 ( 2002-04-05), p. 79-92
    Abstract: We have produced a draft sequence of the rice genome for the most widely cultivated subspecies in China, Oryza sativa L. ssp. indica , by whole-genome shotgun sequencing. The genome was 466 megabases in size, with an estimated 46,022 to 55,615 genes. Functional coverage in the assembled sequences was 92.0%. About 42.2% of the genome was in exact 20-nucleotide oligomer repeats, and most of the transposons were in the intergenic regions between genes. Although 80.6% of predicted Arabidopsis thaliana genes had a homolog in rice, only 49.4% of predicted rice genes had a homolog in A. thaliana . The large proportion of rice genes with no recognizable homologs is due to a gradient in the GC content of rice coding sequences.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2002
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  • 8
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 316, No. 5828 ( 2007-05-25), p. 1181-1184
    Abstract: How anthropogenic climate change will affect hydroclimate in the arid regions of southwestern North America has implications for the allocation of water resources and the course of regional development. Here we show that there is a broad consensus among climate models that this region will dry in the 21st century and that the transition to a more arid climate should already be under way. If these models are correct, the levels of aridity of the recent multiyear drought or the Dust Bowl and the 1950s droughts will become the new climatology of the American Southwest within a time frame of years to decades.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2007
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  • 9
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 12 ( 2020-03-24), p. 6762-6770
    Abstract: Nematode-trapping fungi (NTF) are a group of specialized microbial predators that consume nematodes when food sources are limited. Predation is initiated when conserved nematode ascaroside pheromones are sensed, followed by the development of complex trapping devices. To gain insights into the coevolution of this interkingdom predator–prey relationship, we investigated natural populations of nematodes and NTF that we found to be ubiquitous in soils. Arthrobotrys species were sympatric with various nematode species and behaved as generalist predators. The ability to sense prey among wild isolates of Arthrobotrys oligospora varied greatly, as determined by the number of traps after exposure to Caenorhabditis elegans . While some strains were highly sensitive to C. elegans and the nematode pheromone ascarosides, others responded only weakly. Furthermore, strains that were highly sensitive to the nematode prey also developed traps faster. The polymorphic nature of trap formation correlated with competency in prey killing, as well as with the phylogeny of A. oligospora natural strains, calculated after assembly and annotation of the genomes of 20 isolates. A chromosome-level genome assembly and annotation were established for one of the most sensitive wild isolates, and deletion of the only G-protein β-subunit–encoding gene of A. oligospora nearly abolished trap formation. In summary, our study establishes a highly responsive A. oligospora wild isolate as a model strain for the study of fungus–nematode interactions and demonstrates that trap formation is a fitness character in generalist predators of the nematode-trapping fungus family.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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  • 10
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 33 ( 2020-08-18), p. 20117-20126
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 33 ( 2020-08-18), p. 20117-20126
    Abstract: t(8;21)(q22;q22) acute myelogenous leukemia (AML) is morphologically characterized by a continuum of heterogeneous leukemia cells from myeloblasts to differentiated myeloid elements. Thus, t(8;21) AML is an excellent model for studying heterogeneous cell populations and cellular evolution during disease progression. Using integrative analyses of immunophenotype, RNA-sequencing (RNA-seq), and single-cell RNA-sequencing (scRNA-seq), we identified three distinct intrapatient leukemic cell populations that were arrested at different stages of myeloid differentiation: CD34 + CD117 dim blasts, CD34 + CD117 bri blasts, and abnormal myeloid cells with partial maturation (AM). CD117 is also known as c-KIT protein. CD34 + CD117 dim cells were blocked in the G0/G1 phase at disease onset, presenting with the regular morphology of myeloblasts showing features of granulocyte-monocyte progenitors (GMP), and were drug-resistant to chemotherapy. Genes associated with cell migration and adhesion ( LGALS1 , EMP3 , and ANXA 2 ) were highly expressed in the CD34 + CD117 dim population. CD34 + CD117 bri blasts were blocked a bit later than the CD34 + CD117 dim population in the hematopoietic differentiation stage and displayed high proliferation ability. AM cells, which bear abnormal myelocyte morphology, especially overexpressed granule genes AZU1 , ELANE , and PRTN3 and were sensitive to chemotherapy. scRNA-seq at different time points identified CD34 + CD117 dim blasts as an important leukemic cluster that expanded at postrelapse refractory stage after several cycles of chemotherapy. Patients with t (8;21) AML with a higher proportion of CD34 + CD117 dim cells had significantly worse clinical outcomes than those with a lower CD34 + CD117 dim proportion. Univariate and multivariate analyses identified CD34 + CD117 dim proportion as an independent factor for poor disease outcome. Our study provides evidence for the multidimensional heterogeneity of t(8;21)AML and may offer new tools for future disease stratification.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
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