14 research outputs found

    Desiccation cracks provide evidence of lake drying on Mars, Sutton Island member, Murray formation, Gale Crater

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    Mars Science Laboratory (MSL) Curiosity rover data are used to describe the morphology of desiccation cracks observed in ancient lacustrine strata at Gale crater, Mars, and to interpret their paleoenvironmental setting. The desiccation cracks indicate subaerial exposure of lacustrine facies in the Sutton Island member of the Murray formation. In association with ripple cross-stratification and possible eolian cross-bedding, these facies indicate a transition from longer-lived perennial lakes recorded by older strata to younger lakes characterized by intermittent exposure. The transition from perennial to episodically exposed lacustrine environments provides evidence for local to regional climate change that can help constrain Mars climate models

    The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

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    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)

    Functional genomics and evolution of tick–Anaplasma interactions and vaccine development

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    The genus Anaplasma (Rickettsiales: Anaplasmataceae) includes several tick-transmitted pathogens that impact veterinary and human health. Tick-borne pathogens cycle between tick vectors and vertebrate hosts and their interaction is mediated by molecular mechanisms at the tick–pathogen interface. These mechanisms have evolved characteristics that involve traits from both the tick vector and the pathogen to insure their mutual survival. Herein, we review the information obtained from functional genomics and genetic studies to characterize the tick–Anaplasma interface and evolution of A. marginale and A. phagocytophilum. Anaplasma and tick genes and proteins involved in tick–pathogen interactions were characterized. The results of these studies demonstrated that common and Anaplasma species-specific molecular mechanism occur by which pathogen and tick cell gene expression mediates or limits Anaplasma developmental cycle and trafficking through ticks. These results have advanced our understanding of the biology of tick–Anaplasma interactions and have opened new avenues for the development of improved methods for the control of tick infestations and the transmission of tick-borne pathogens.Fil: de la Fuente, José. Oklahoma State University; Estados Unidos. Consejo Superior de Investigaciones Científicas; EspañaFil: Kocan, Katherine M.. Oklahoma State University; Estados UnidosFil: Blouin, Edmour F.. Oklahoma State University; Estados UnidosFil: Zivkovic, Zorica. Utrecht University; Países BajosFil: Naranjo, Victoria. Oklahoma State University; Estados Unidos. Oklahoma State University; Estados UnidosFil: Almazán, Consuelo. Universidad Autónoma de Tamaulipas; MéxicoFil: Esteves, Eliane. Universidade de Sao Paulo; BrasilFil: Jongejan, Frans. Utrecht University; Países Bajos. University of Pretoria; SudáfricaFil: Daffre, Sirlei. Universidade de Sao Paulo; BrasilFil: Mangold, Atilio Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Tecnológica Nacional. Facultad Regional Rafaela; Argentin
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