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"Jones, Terry"
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Re-assessing the diversity of negative strand RNA viruses in insects
The spectrum of viruses in insects is important for subjects as diverse as public health, veterinary medicine, food production, and biodiversity conservation. The traditional interest in vector-borne diseases of humans and livestock has drawn the attention of virus studies to hematophagous insect species. However, these represent only a tiny fraction of the broad diversity of Hexapoda, the most speciose group of animals. Here, we systematically probed the diversity of negative strand RNA viruses in the largest and most representative collection of insect transcriptomes from samples representing all 34 extant orders of Hexapoda and 3 orders of Entognatha, as well as outgroups, altogether representing 1243 species. Based on profile hidden Markov models we detected 488 viral RNA-directed RNA polymerase (RdRp) sequences with similarity to negative strand RNA viruses. These were identified in members of 324 arthropod species. Selection for length, quality, and uniqueness left 234 sequences for analyses, showing similarity to genomes of viruses classified in Bunyavirales (n = 86), Articulavirales (n = 54), and several orders within Haploviricotina (n = 94). Coding-complete genomes or nearly-complete subgenomic assemblies were obtained in 61 cases. Based on phylogenetic topology and the availability of coding-complete genomes we estimate that at least 20 novel viral genera in seven families need to be defined, only two of them monospecific. Seven additional viral clades emerge when adding sequences from the present study to formerly monospecific lineages, potentially requiring up to seven additional genera. One long sequence may indicate a novel family. For segmented viruses, cophylogenies between genome segments were generally improved by the inclusion of viruses from the present study, suggesting that in silico misassembly of segmented genomes is rare or absent. Contrary to previous assessments, significant virus-host codivergence was identified in major phylogenetic lineages based on two different approaches of codivergence analysis in a hypotheses testing framework. In spite of these additions to the known spectrum of viruses in insects, we caution that basing taxonomic decisions on genome information alone is challenging due to technical uncertainties, such as the inability to prove integrity of complete genome assemblies of segmented viruses.
Journal Article
Red and Yellow Hypergiants
The red and yellow hypergiants are a rare and important phase in the evolution of the most massive stars that can reach the cool part of the HR Diagram. The hypergiant phase is commonly characterized by high, often episodic mass-loss rates and significant changes in spectral type, probably due to the formation of a pseudo photopsphere during a high mass-loss episode. Many of the yellow hypergiants are the immediate successors to the most luminous red supergiants, and often show evidence in their dusty, circumstellar envelopes from past red supergiant activity. In this paper we review the yellow and red hypergiants with an emphasis on how they differ from more normal red supergiants.
Journal Article
Violence and warfare among hunter-gatherers
\"How did warfare originate? Was it human genetics? Social competition? The rise of complexity? Intensive study of the long-term hunter-gatherer past brings us closer to an answer. The original chapters in this volume examine cultural areas on five continents where there is archaeological, ethnographic, and historical evidence for hunter-gatherer conflict despite high degrees of mobility, small populations, and relatively egalitarian social structures. Their controversial conclusions will elicit interest among anthropologists, archaeologists, and those in conflict studies.\"-- Provided by publisher.
Book
Virological assessment of hospitalized patients with COVID-2019
Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 2019
1
,
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. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses
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. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung
2
,
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; the same receptor tropism is thought to have determined the pathogenicity—but also aided in the control—of severe acute respiratory syndrome (SARS) in 2003
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. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission
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–
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. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 10
8
RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples—in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.
Detailed virological analysis of nine cases of coronavirus disease 2019 (COVID-19) provides proof of active replication of the SARS-CoV-2 virus in tissues of the upper respiratory tract.
Journal Article
Gorillas in our midst
Reveals that gorillas, those masters of disguise and experts at hiding, are all around us and invites the reader to seek gorillas of all ages in the illustrations, while carrying a banana just in case.
Book
OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation
Activation of the NLRP3 inflammasome induces maturation of IL-1β and IL-18, both validated targets for treating acute and chronic inflammatory diseases. Here, we demonstrate that OLT1177, an orally active β-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar concentrations of OLT1177 reduced IL-1β and IL-18 release following canonical and noncanonical NLRP3 inflammasome activation. The molecule showed no effect on the NLRC4 and AIM2 inflammasomes, suggesting specificity for NLRP3. In LPS-stimulated human blood-derived macrophages, OLT1177 decreased IL-1β levels by 60% and IL-18 by 70% at concentrations 100-fold lower in vitro than plasma concentrations safely reached in humans. OLT1177 also reduced IL-1β release and caspase-1 activity in freshly obtained human blood neutrophils. In monocytes isolated from patients with cryopyrin-associated periodic syndrome (CAPS), OLT1177 inhibited LPS-induced IL-1β release by 84% and 36%. Immunoprecipitation and FRET analysis demonstrated that OLT1177 prevented NLRP3-ASC, as well as NLRP3-caspase-1 interaction, thus inhibiting NLRP3 inflammasome oligomerization. In a cell-free assay, OLT1177 reduced ATPase activity of recombinant NLRP3, suggesting direct targeting of NLRP3. Mechanistically, OLT1177 did not affect potassium efflux, gene expression, or synthesis of the IL-1β precursor. Steady-state levels of phosphorylated NF-κB and IkB kinase were significantly lowered in spleen cells from OLT1177-treated mice. We observed reduced IL-1β content in tissue homogenates, limited oxidative stress, and increased muscle oxidative metabolism in OLT1177-treated mice challenged with LPS. Healthy humans receiving 1,000 mg of OLT1177 daily for 8 d exhibited neither adverse effects nor biochemical or hematological changes.
Journal Article
Technical opportunities and challenges in developing total-body PET scanners for mice and rats
Positron emission tomography (PET) is the most sensitive in vivo molecular imaging technique available. Small animal PET has been widely used in studying pharmaceutical biodistribution and disease progression over time by imaging a wide range of biological processes. However, it remains true that almost all small animal PET studies using mouse or rat as preclinical models are either limited by the spatial resolution or the sensitivity (especially for dynamic studies), or both, reducing the quantitative accuracy and quantitative precision of the results. Total-body small animal PET scanners, which have axial lengths longer than the nose-to-anus length of the mouse/rat and can provide high sensitivity across the entire body of mouse/rat, can realize new opportunities for small animal PET. This article aims to discuss the technical opportunities and challenges in developing total-body small animal PET scanners for mice and rats.
Journal Article