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  • 1
    Online Resource
    Online Resource
    Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome
    American Association for the Advancement of Science (AAAS) ; 2020
    In:  Science Signaling Vol. 13, No. 635 ( 2020-06-09)
    Details
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 13, No. 635 ( 2020-06-09)
    Abstract: Zika virus (ZIKV) infection during pregnancy can cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments with animal models and in vitro systems have substantially contributed to our understanding of the pathophysiology of ZIKV infection. Here, to investigate the molecular basis of CZS in humans, we used a systems biology approach to integrate transcriptomic, proteomic, and genomic data from the postmortem brains of neonates with CZS. We observed that collagens were greatly reduced in expression in CZS brains at both the RNA and protein levels and that neonates with CZS had several single-nucleotide polymorphisms in collagen-encoding genes that are associated with osteogenesis imperfecta and arthrogryposis. These findings were validated by immunohistochemistry and comparative analysis of collagen abundance in ZIKV-infected and uninfected samples. In addition, we showed a ZIKV-dependent increase in the expression of cell adhesion factors that are essential for neurite outgrowth and axon guidance, findings that are consistent with the neuronal migration defects observed in CZS. Together, these findings provide insights into the underlying molecular alterations in the ZIKV-infected brain and reveal host genes associated with CZS susceptibility.
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    URL: Article
    DOI: 10.1126/scisignal.aay6736
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2020
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  • 2
    Online Resource
    Online Resource
    Genome-wide signatures of complex introgression and adaptive evolution in the big cats
    American Association for the Advancement of Science (AAAS) ; 2017
    In:  Science Advances Vol. 3, No. 7 ( 2017-07-07)
    Details
    In: Science Advances, American Association for the Advancement of Science (AAAS), Vol. 3, No. 7 ( 2017-07-07)
    Abstract: The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar ( Panthera onca ) genome, a novel genome sequence for the leopard ( Panthera pardus ), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes ( DOCK3 and COL4A5 , both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages.
    Type of Medium: Online Resource
    ISSN: 2375-2548
    URL: Article
    DOI: 10.1126/sciadv.1700299
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
    detail.hit.zdb_id: 2810933-8
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  • 3
    Online Resource
    Online Resource
    Zika virus in the Americas: Early epidemiological and genetic findings
    American Association for the Advancement of Science (AAAS) ; 2016
    In:  Science Vol. 352, No. 6283 ( 2016-04-15), p. 345-349
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 352, No. 6283 ( 2016-04-15), p. 345-349
    Abstract: Brazil has experienced an unprecedented epidemic of Zika virus (ZIKV), with ~30,000 cases reported to date. ZIKV was first detected in Brazil in May 2015, and cases of microcephaly potentially associated with ZIKV infection were identified in November 2015. We performed next-generation sequencing to generate seven Brazilian ZIKV genomes sampled from four self-limited cases, one blood donor, one fatal adult case, and one newborn with microcephaly and congenital malformations. Results of phylogenetic and molecular clock analyses show a single introduction of ZIKV into the Americas, which we estimated to have occurred between May and December 2013, more than 12 months before the detection of ZIKV in Brazil. The estimated date of origin coincides with an increase in air passengers to Brazil from ZIKV-endemic areas, as well as with reported outbreaks in the Pacific Islands. ZIKV genomes from Brazil are phylogenetically interspersed with those from other South American and Caribbean countries. Mapping mutations onto existing structural models revealed the context of viral amino acid changes present in the outbreak lineage; however, no shared amino acid changes were found among the three currently available virus genomes from microcephaly cases. Municipality-level incidence data indicate that reports of suspected microcephaly in Brazil best correlate with ZIKV incidence around week 17 of pregnancy, although this correlation does not demonstrate causation. Our genetic description and analysis of ZIKV isolates in Brazil provide a baseline for future studies of the evolution and molecular epidemiology of this emerging virus in the Americas.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aaf5036
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2016
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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