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1.
Science ; 378(6619): 560-565, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36264825

ABSTRACT

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.


Subject(s)
APOBEC Deaminases , Host-Pathogen Interactions , Monkeypox virus , Mpox (monkeypox) , RNA Editing , Humans , Mpox (monkeypox)/enzymology , Mpox (monkeypox)/virology , Monkeypox virus/genetics , Monkeypox virus/isolation & purification , Nigeria/epidemiology , United States/epidemiology , Mutation , Evolution, Molecular , APOBEC Deaminases/metabolism , Adenosine/genetics , Cytidine/genetics
2.
Biosecur Bioterror ; 12(1): 49-62, 2014.
Article in English | MEDLINE | ID: mdl-24552362

ABSTRACT

Abrin is a heterodimeric toxin present in the seeds of the Abrus precatorius plant. The easily obtainable seeds can yield a highly toxic product that can be used in various types of biocrimes and terrorism-related activities, including "white-powder" letters. Although the vast majority of these threats are hoaxes, the lack of rapid and reliable detection assays for abrin, such as lateral flow assays (LFAs), can be an impediment to accurate and rapid hazard assessment. One of the complicating factors associated with LFAs is the use of antibodies of poor affinity and specificity that cross-react with near neighbors or that bind to plant lectins, which are capable of nonspecifically cross-linking the capture and detector antibodies. Because of the critical need to promote public safety and public health, we conducted a comprehensive laboratory evaluation of a commercial LFA for the rapid detection of abrin. This study was conducted using comprehensive inclusivity and exclusivity panels of abrin and near-neighbor plant materials, along with panels of lectins, related proteins, white powders, and environmental background material, to determine the sensitivity, specificity, limit of detection, dynamic range, and repeatability of the assay for the specific intended use of evaluating suspicious white powders and environmental samples for the presumptive presence of abrin.


Subject(s)
Abrin/isolation & purification , Powders/chemistry , Reagent Kits, Diagnostic/standards , Chemical Terrorism , Powders/poisoning , Reagent Strips , Sensitivity and Specificity , United States
3.
Expert Rev Mol Med ; 11: e3, 2009 Jan 20.
Article in English | MEDLINE | ID: mdl-19152719

ABSTRACT

There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.


Subject(s)
Inflammation/immunology , Nervous System/immunology , Nervous System/pathology , Neuroimmunomodulation/physiology , Receptor, Cannabinoid, CB2/immunology , Amino Acid Sequence , Animals , Humans , Molecular Sequence Data , Receptor, Cannabinoid, CB2/chemistry , Research
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