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The SARS-CoV-2 virus has infected more than 261 million people and has led to more than 5 million deaths in the past year and a half1 ( https://www.who.org/ ). Individuals with SARS-CoV-2 infection typically develop mild-to-severe flu-like symptoms, whereas infection of a subset of individuals leads to severe-to-fatal clinical outcomes2. Although vaccines have been rapidly developed to combat SARS-CoV-2, there has been a dearth of antiviral therapeutics. There is an urgent need for therapeutics, which has been amplified by the emerging threats of variants that may evade vaccines. Large-scale efforts are underway to identify antiviral drugs. Here we screened approximately 18,000 drugs for antiviral activity using live virus infection in human respiratory cells and validated 122 drugs with antiviral activity and selectivity against SARS-CoV-2. Among these candidates are 16 nucleoside analogues, the largest category of clinically used antivirals. This included the antivirals remdesivir and molnupiravir, which have been approved for use in COVID-19. RNA viruses rely on a high supply of nucleoside triphosphates from the host to efficiently replicate, and we identified a panel of host nucleoside biosynthesis inhibitors as antiviral. Moreover, we found that combining pyrimidine biosynthesis inhibitors with antiviral nucleoside analogues synergistically inhibits SARS-CoV-2 infection in vitro and in vivo against emerging strains of SARS-CoV-2, suggesting a clinical path forward.
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Antivirais , Avaliação Pré-Clínica de Medicamentos , Nucleosídeos , Pirimidinas , SARS-CoV-2 , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , COVID-19/virologia , Linhagem Celular , Citidina/análogos & derivados , Humanos , Hidroxilaminas , Nucleosídeos/análogos & derivados , Nucleosídeos/farmacologia , Pirimidinas/farmacologia , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
Wildfires may facilitate climate tracking of forest species moving upslope or north in latitude. For subalpine tree species, for which higher elevation habitat is limited, accelerated replacement by lower elevation montane tree species following fire may hasten extinction risk. We used a dataset of postfire tree regeneration spanning a broad geographic range to ask whether the fire facilitated upslope movement of montane tree species at the montane-to-subalpine ecotone. We sampled tree seedling occurrence in 248 plots across a fire severity gradient (unburned to >90% basal area mortality) and spanning ~500 km of latitude in Mediterranean-type subalpine forest in California, USA. We used logistic regression to quantify differences in postfire regeneration between resident subalpine species and the seedling-only range (interpreted as climate-induced range extension) of montane species. We tested our assumption of increasing climatic suitability for montane species in subalpine forest using the predicted difference in habitat suitability at study plots between 1990 and 2030. We found that postfire regeneration of resident subalpine species was uncorrelated or weakly positively correlated with fire severity. Regeneration of montane species, however, was roughly four times greater in unburned relative to burned subalpine forest. Although our overall results contrast with theoretical predictions of disturbance-facilitated range shifts, we found opposing postfire regeneration responses for montane species with distinct regeneration niches. Recruitment of shade-tolerant red fir declined with fire severity and recruitment of shade-intolerant Jeffrey pine increased with fire severity. Predicted climatic suitability increased by 5% for red fir and 34% for Jeffrey pine. Differing postfire responses in newly climatically available habitats indicate that wildfire disturbance may only facilitate range extensions for species whose preferred regeneration conditions align with increased light and/or other postfire landscape characteristics.
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Pinus , Incêndios Florestais , Ecossistema , Incêndios , Florestas , Plântula , ÁrvoresRESUMO
The Late Devonian was a protracted period of low speciation resulting in biodiversity decline, culminating in extinction events near the Devonian-Carboniferous boundary. Recent evidence indicates that the final extinction event may have coincided with a dramatic drop in stratospheric ozone, possibly due to a global temperature rise. Here we study an alternative possible cause for the postulated ozone drop: a nearby supernova explosion that could inflict damage by accelerating cosmic rays that can deliver ionizing radiation for up to [Formula: see text] ky. We therefore propose that the end-Devonian extinctions were triggered by supernova explosions at [Formula: see text], somewhat beyond the "kill distance" that would have precipitated a full mass extinction. Such nearby supernovae are likely due to core collapses of massive stars; these are concentrated in the thin Galactic disk where the Sun resides. Detecting either of the long-lived radioisotopes [Formula: see text] or [Formula: see text] in one or more end-Devonian extinction strata would confirm a supernova origin, point to the core-collapse explosion of a massive star, and probe supernova nucleosynthesis. Other possible tests of the supernova hypothesis are discussed.
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Radiação Cósmica/efeitos adversos , Extinção Biológica , Fósseis/história , Biodiversidade , Meio Ambiente Extraterreno/química , História Antiga , Astros CelestesRESUMO
Polyarticular joint pain involves five or more joints and can be inflammatory or noninflammatory. Two of the most common causes of chronic polyarthritis are osteoarthritis, especially in older patients, and rheumatoid arthritis, which affects at least 0.25% of adults worldwide. The initial evaluation should include a detailed history of the patient's symptoms, with a focus on inflammation, location of pain, duration of symptoms, the presence of systemic symptoms, and any exposures to pathogens that could cause arthritis. Redness, warmth, or swelling in a joint is suggestive of synovitis and joint inflammation. A systematic approach to the physical examination that assesses for a pattern of joint involvement and presence of synovitis can help narrow the differential diagnosis. Laboratory tests, joint aspiration, and imaging studies should be used to confirm a suspected diagnosis. Rheumatoid factor and cyclic citrullinated peptide antibody tests are helpful when there is concern for rheumatoid arthritis. Although magnetic resonance imaging is highly sensitive in identifying erosive bony changes and inflammation, conventional radiography remains the standard for the initial imaging evaluation of rheumatoid arthritis. Point-of-care musculoskeletal ultrasonography can also be a useful tool to detect findings that support a diagnosis of inflammatory arthritis.
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Artrite Reumatoide , Sinovite , Humanos , Adulto , Idoso , Diagnóstico Diferencial , Artrite Reumatoide/diagnóstico , Sinovite/diagnóstico , Sinovite/patologia , Inflamação , Imageamento por Ressonância Magnética/métodos , Artralgia/diagnósticoRESUMO
While climate change has already profoundly influenced biodiversity through local extinctions, range shifts, and altered interactions, its effects on the evolutionary history contained within sets of coexisting species-or phylogenetic community diversity-have yet to be documented. Phylogenetic community diversity may be a proxy for the diversity of functional strategies that can help sustain ecological systems in the face of disturbances. Under climatic warming, phylogenetic diversity may be especially vulnerable to decline in plant communities in warm, water-limited regions, as intensified water stress eliminates drought-intolerant species that may be relicts of past wetter climates and may be distantly related to coexisting species. Here, we document a 19-y decline of phylogenetic diversity in a grassland community as moisture became less abundant and predictable at a critical time of the year. This decline was strongest in native forbs, particularly those with high specific leaf area, a trait indicating drought sensitivity. This decline occurred at the small spatial scale where species interact, but the larger regional community has so far been buffered against loss of phylogenetic diversity by its high levels of physical and biotic heterogeneity.
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Biodiversidade , Mudança Climática , Pradaria , Filogenia , Plantas/classificação , California , Secas , Fenótipo , Análise de Regressão , Estações do Ano , ÁguaRESUMO
Exotic invasive plants threaten ecosystem integrity, and their success depends on a combination of abiotic factors, disturbances, and interactions with existing communities. In dryland ecosystems, soil biocrusts (communities of lichens, bryophytes, and microorganisms) can limit favorable microsites needed for invasive species establishment, but the relative importance of biocrusts for landscape-scale invasion patterns remains poorly understood. We examine effects of livestock grazing in habitats at high risk for invasion to test the hypothesis that disturbance indirectly favors exotic annual grasses by reducing biocrust cover. We present some of the first evidence that biocrusts increase site resistance to invasion at a landscape scale and mediate the effects of disturbance. Biocrust species richness, which is reduced by livestock grazing, also appears to promote native perennial grasses. Short mosses, as a functional group, appear to be particularly valuable for preventing invasion by exotic annual grasses. Our study suggests that maintaining biocrust communities with high cover, species richness, and cover of short mosses can increase resistance to invasion. These results highlight the potential of soil surface communities to mediate invasion dynamics and suggest promising avenues for restoration in dryland ecosystems.
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Briófitas , Líquens , Ecossistema , Poaceae , SoloRESUMO
Maca (Lepidium meyenii, synonym L. peruvianum) was analyzed using a systematic approach employing principal component analysis of flow injection mass spectrometry fingerprints (no chromatographic separation) to guide the selection of samples for metabolite profiling and DNA next generation sequencing. Samples consisted of 39 commercial maca supplements from 11 manufacturers, 31 unprocessed maca tubers grown in Peru and China, and a historic non-tuber maca sample from Peru. Principal component analysis of flow injection mass spectrometry fingerprints initially placed all the maca samples in three classes with similar chemical composition: commercial maca samples, tubers grown in Peru, and tubers grown in China. Metabolite profiling identified 67 compounds in the negative mode and 51 compounds in the positive mode. Compounds identified by metabolite profiling (macamides, glucosinolates, amino acids, fatty acids, polyunsaturated fatty acids, saccharides, imidazoles) were then used to identify ions in the flow injection mass spectrometry fingerprints. The tuber fingerprints were analyzed by factorial multivariate analysis of variance revealing that black, red, and yellow maca from Peru and black and yellow maca from China were compositionally different with respect to color and country. Critical ions were identified that allowed for the differentiation of maca between colors from the same country or between two countries with the same color. Genetically, all samples were confirmed to be L. meyenii based on next generation sequencing at three gene regions (ITS2, psbA, and trnL) and comparison to recorded sequences of vouchered standards.
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Lepidium , China , Metabolômica , Peru , Extratos VegetaisRESUMO
Many global ecosystems have undergone shifts in fire regimes in recent decades, such as changes in fire size, frequency, and/or severity. Recent research shows that increases in fire size, frequency, and severity can lead to long-persisting deforestation, but the consequences of shifting fire regimes for biodiversity of other vegetative organisms (such as understory plants, fungi, and lichens) remain poorly understood. Understanding lichen responses to wildfire is particularly important because lichens play crucial roles in nutrient cycling and supporting wildlife in many ecosystems. Lichen responses to fire have been little studied, and most previous research has been limited to small geographic areas (e.g. studies of a single fire), making it difficult to establish generalizable patterns. To investigate long-term effects of fire severity on lichen communities, we sampled epiphytic lichen communities in 104 study plots across California's greater Sierra Nevada region in areas that burned in five wildfires, ranging from 4 to 16 years prior to sampling. The conifer forest ecosystems we studied have undergone a notable increase in fire severity in recent decades, and we sample across the full gradient of fire severity to infer how shifting fire regimes may influence landscape-level biodiversity. We find that low-severity fire has little to no effect on lichen communities. Areas that burned at moderate and high severities, however, have significantly and progressively lower lichen richness and abundance. Importantly, we observe very little postfire lichen recolonization on burned substrates even more than 15 years after fire. Our multivariate model suggests that the hotter, drier microclimates that occur after fire removes forest canopies may prevent lichen reestablishment, meaning that lichens are not likely to recolonize until mature trees regenerate. These findings suggest that altered fire regimes may cause broad and long-persisting landscape-scale biodiversity losses that could ultimately impact multiple trophic levels.
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Biodiversidade , Incêndios , Florestas , Líquens/classificação , California , Conservação dos Recursos Naturais , Monitoramento Ambiental , Líquens/crescimento & desenvolvimento , Modelos Teóricos , Traqueófitas/crescimento & desenvolvimento , Árvores/crescimento & desenvolvimentoRESUMO
Perennial grasses are promising feedstocks for bioenergy production in the Midwestern USA. Few experiments have addressed how drought influences their carbon fluxes and storage. This study provides a direct comparison of ecosystem-scale measurements of carbon fluxes associated with miscanthus (Miscanthus × giganteus), switchgrass (Panicum virgatum), restored native prairie and maize (Zea mays)/soybean (Glycine max) ecosystems. The main objective of this study was to assess the influence of a naturally occurring drought during 2012 on key components of the carbon cycle and plant development relative to non-extreme years. The perennials reached full maturity 3-5 years after establishment. Miscanthus had the highest gross primary production (GPP) and lowest net ecosystem exchange (NEE) in 2012 followed by similar values for switchgrass and prairie, and the row crops had the lowest GPP and highest NEE. A post-drought effect was observed for miscanthus. Over the duration of the experiment, perennial ecosystems were carbon sinks, as indicated by negative net ecosystem carbon balance (NECB), while maize/soybean was a net carbon source. Our observations suggest that perennial ecosystems, and in particular miscanthus, can provide a high yield and a large potential for CO2 fixation even during drought, although drought may negatively influence carbon uptake in the following year, questioning the long-term consequence of its maintained productivity.
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Biocombustíveis , Biomassa , Dióxido de Carbono/metabolismo , Secas , Poaceae/metabolismo , Resposta ao Choque Térmico , IllinoisRESUMO
The potential impacts of climate change in the Midwest United States present unprecedented challenges to regional agriculture. In response to these challenges, a variety of climate-smart agricultural methodologies have been proposed to retain or improve crop yields, reduce agricultural greenhouse gas emissions, retain soil quality and increase climate resilience of agricultural systems. One component that is commonly neglected when assessing the environmental impacts of climate-smart agriculture is the biophysical impacts, where changes in ecosystem fluxes and storage of moisture and energy lead to perturbations in local climate and water availability. Using a combination of observational data and an agroecosystem model, a series of climate-smart agricultural scenarios were assessed to determine the biophysical impacts these techniques have in the Midwest United States. The first scenario extended the growing season for existing crops using future temperature and CO2 concentrations. The second scenario examined the biophysical impacts of no-till agriculture and the impacts of annually retaining crop debris. Finally, the third scenario evaluated the potential impacts that the adoption of perennial cultivars had on biophysical quantities. Each of these scenarios was found to have significant biophysical impacts. However, the timing and magnitude of the biophysical impacts differed between scenarios.
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Agricultura/métodos , Clima , Produtos Agrícolas , Modelos Teóricos , Biofísica , Dióxido de Carbono , Produtos Agrícolas/crescimento & desenvolvimento , Ecossistema , Meio Ambiente , Meio-Oeste dos Estados Unidos , Estações do Ano , Glycine max/crescimento & desenvolvimento , Temperatura , Zea mays/crescimento & desenvolvimentoRESUMO
Understanding how biotic communities respond to landscape spatial structure is critically important for conservation management as natural habitats become increasingly fragmented. However, empirical studies of the effects of spatial structure on plant species richness have found inconsistent results, suggesting that more comprehensive approaches are needed. We asked how landscape structure affects total plant species richness and the richness of a guild of specialized plants in a multivariate context. We sampled herbaceous plant communities at 56 dolomite glades (insular, fire-adapted grasslands) across the Missouri Ozarks, USA, and used structural equation modeling (SEM) to analyze the relative importance of landscape structure, soil resource availability, and fire history for plant communities. We found that landscape spatial structure, defined as the area-weighted proximity of glade habitat surrounding study sites (proximity index), had a significant effect on total plant species richness, but only after we controlled for environmental covariates. Richness of specialist species, but not generalists, was positively related to landscape spatial structure. Our results highlight that local environmental filters must be considered to understand the influence of landscape structure on communities and that unique species guilds may respond differently to landscape structure than the community as a whole. These findings suggest that both local environment and landscape context should be considered when developing management strategies for species of conservation concern in fragmented habitats.
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Pradaria , Plantas/classificação , Animais , Incêndios , Fenômenos Geológicos , Missouri , Desenvolvimento Vegetal , Solo/químicaRESUMO
Rubella is a highly contagious viral infection that usually causes a mild disease in children and adults. However, infection during pregnancy can result in a fetal or newborn death or congenital rubella syndrome (CRS), a constellation of permanent birth defects including cataracts, heart defects, and sensorineural deafness. The live-attenuated rubella vaccine has been highly effective, with the Americas declared free of endemic rubella transmission in 2015. However, rubella remains a significant problem worldwide and the leading cause of vaccine-preventable birth defects globally. Thus, elimination of rubella and CRS is a goal of the World Health Organization. No specific therapeutics are approved for the rubella virus. Therefore, we set out to identify whether existing small molecules may be repurposed for use against rubella virus infection. Thus, we performed a high-throughput screen for small molecules active against rubella virus in human respiratory cells and identified two nucleoside analogs, NM107 and AT-527, with potent antiviral activity. Furthermore, we found that combining these nucleoside analogs with inhibitors of host nucleoside biosynthesis had synergistic antiviral activity. These studies open the door to new potential approaches to treat rubella infections.
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The ability of a virus to infect a cell type is at least in part determined by the presence of host factors required for the viral life cycle. However, even within cell types that express known factors needed for infection, not every cell is equally susceptible, suggesting that our knowledge of the full spectrum of factors that promote infection is incomplete. Profiling the most susceptible subsets of cells within a population may reveal additional factors that promote infection. However, because viral infection dramatically alters the state of the cell, new approaches are needed to reveal the state of these cells prior to infection with virus. Here, we used single-cell clone tracing to retrospectively identify and characterize lung epithelial cells that are highly susceptible to infection with SARS-CoV-2. The transcriptional state of these highly susceptible cells includes markers of retinoic acid signaling and epithelial differentiation. Loss of candidate factors identified by our approach revealed that many of these factors play roles in viral entry. Moreover, a subset of these factors exert control over the infectable cell state itself, regulating the expression of key factors associated with viral infection and entry. Analysis of patient samples revealed the heterogeneous expression of these factors across both cells and patients in vivo. Further, the expression of these factors is upregulated in particular inflammatory pathologies. Altogether, our results show that the variable expression of intrinsic cell states is a major determinant of whether a cell can be infected by SARS-CoV-2.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of deaths, posing a substantial threat to global public health. Viruses evolve different strategies to antagonize or evade host immune responses. While ectopic expression of SARS-CoV-2 accessory protein ORF6 blocks interferon (IFN) production and downstream IFN signaling, the role of ORF6 in IFN signaling during bona fide viral infection of respiratory cells is unclear. By comparing wild-type (WT) and ORF6-deleted (ΔORF6) SARS-CoV-2 infection and IFN signaling in respiratory cells, we found that ΔORF6 SARS-CoV-2 replicates more efficiently than WT virus and, thus, stimulates more robust immune signaling. Loss of ORF6 does not alter innate signaling in infected cells: both WT and ΔORF6 virus induce delayed IFN responses only in bystander cells. Moreover, expression of ORF6 in the context of SARS-CoV-2 infection has no effect on Sendai virus-stimulated IFN induction: robust translocation of IRF3 is observed in both SARS-CoV-2 infected and bystander cells. Furthermore, IFN pretreatment potently blocks WT and ΔORF6 virus replication similarly, and both viruses fail to suppress the induction of interferon-stimulated genes (ISGs) upon IFN-ß treatment. However, upon treatment with IFN-ß, only bystander cells induce STAT1 translocation during infection with WT virus, whereas ΔORF6 virus-infected cells now show translocation. This suggests that under conditions of high IFN activation, ORF6 can attenuate STAT1 activation. These data provide evidence that ORF6 is not sufficient to antagonize IFN production or IFN signaling in SARS-CoV-2-infected respiratory cells but may impact the efficacy of therapeutics that stimulate innate immune pathways. IMPORTANCE Previous studies identified several SARS-CoV-2 proteins, including ORF6, that antagonize host innate immune responses in the context of overexpression of viral proteins in non-respiratory cells. We set out to determine the role of ORF6 in IFN responses during SARS-CoV-2 infection of respiratory cells. Using a deletion strain, we observed no reduction of infection and no difference in evasion of IFN signaling, with responses limited to bystander cells. Moreover, stimulation of Sendai virus-induced IFN production or IFN-ß-stimulated ISG expression was comparable between SARS-CoV-2 virus and SARS-CoV-2 lacking ORF6 virus, suggesting that ORF6 is not sufficient to counteract IFN induction or IFN signaling during viral infection.
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COVID-19 , Interferon Tipo I , Humanos , SARS-CoV-2/metabolismo , Proteínas Virais/metabolismo , Interferons , Imunidade InataRESUMO
SARS-CoV-2 emerged, and is evolving to efficiently infect humans worldwide. SARS-CoV-2 evades early innate recognition, interferon signaling activated only in bystander cells. This balance of innate activation and viral evasion has important consequences, but the pathways involved are incompletely understood. Here we find that autophagy genes regulate innate immune signaling, impacting the basal set point of interferons, and thus permissivity to infection. Mechanistically, autophagy genes negatively regulate MAVS, and this low basal level of MAVS is efficiently antagonized by SARS-CoV-2 ORF9b, blocking interferon activation in infected cells. However, upon loss of autophagy increased MAVS overcomes ORF9b-mediated antagonism suppressing infection. This has led to the evolution of SARS-CoV-2 variants to express higher levels of ORF9b, allowing SARS-CoV-2 to replicate under conditions of increased MAVS signaling. Altogether, we find a critical role of autophagy in the regulation of innate immunity and uncover an evolutionary trajectory of SARS-CoV-2 ORF9b to overcome host defenses.
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Soils derived from ultramafic parent materials (hereafter serpentine) provide habitat for unique plant communities containing species with adaptations to the low nutrient levels, high magnesiumâ:âcalcium ratios, and high metal content (Ni, Zn) that characterize serpentine. Plants on serpentine have long been studied in evolution and ecology, and plants adapted to serpentine contribute disproportionately to plant diversity in many parts of the world. In 2000-2003, serpentine plant communities were sampled at 107 locations representing the full range of occurrence of serpentine in California, USA, spanning large gradients in climate. In 2009-2010, plant communities were similarly sampled at 97 locations on nonserpentine soil, near to and paired with 97 of the serpentine sampling locations. (Some serpentine locations were revisited in 2009-2010 to assess the degree of change since 2000-2003, which was minimal.) At each serpentine or nonserpentine location, a north- and a south-facing 50 × 10 m plot were sampled. This design produced 97 "sites" each consisting of four "plots" (north-south exposure, serpentine-nonserpentine soil). All plots were initially visited three or more times over two years to record plant diversity and cover, and a subset were revisited in 2014 to examine community change after a drought. The original question guiding the study was how plant diversity is shaped by the spatially patchy nature of the serpentine habitat. Subsequently, we investigated how climate drives plant diversity at multiple scales (within locations, between locations on the same and different soil types, and across entire regions) and at different levels of organization (taxonomic, functional, and phylogenetic). There are no copyright restrictions and users should cite this data paper in publications that result from use of the data.
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Plantas , Solo , Ecossistema , Filogenia , Microbiologia do SoloRESUMO
Although severe cases and mortality of coronavirus disease 2019 (COVID-19) are proportionally infrequent, these cases are strongly linked to patients with conditions of metabolic syndrome (obesity, hypertension, diabetes, and dyslipidemia). However, the pathophysiology of COVID-19 in relation to metabolic syndrome is not well understood. Thus, the goal of this secondary literature review was to examine the relationship between severe acute respiratory syndrome (SARS-CoV-2) infection and the individual conditions of metabolic syndrome. The objective of this secondary literature review was achieved by examining primary studies, case studies, and other secondary studies, to obtain a comprehensive perspective of theories and observations of COVID-19 etiology with metabolic syndrome. The most extensive research was available on the topics of diabetes, hypertension, and obesity, which yielded multiple (and sometimes conflicting) hypothetical pathophysiology. The sources on dyslipidemia and COVID-19 were scarcer and failed to provide an equally comprehensive image, highlighting the need for further research. It was concluded that hypertension had the strongest correlation with COVID-19 incidence (followed by obesity), yet the causative pathophysiology was ambiguous; most likely related to cardiovascular, angiotensin-converting enzyme 2 (ACE-2)-related complications from renin-angiotensin-aldosterone system (RAAS) imbalance. Obesity was also positively correlated to the severity of COVID-19 cases and was believed to contribute to mechanical difficulties with respiration, in addition to hypothetical connections with the expression of ACE-2 on abundant adipose tissue. Diabetes was believed to contribute to COVID-19 severity by producing a chronic inflammatory state and interfering with neutrophil and T-cell function. Furthermore, there were indications that COVID-19 may induce acute-onset diabetes and diabetic ketoacidosis. Lastly, dyslipidemia was concluded to potentially facilitate SARS-CoV-2 infection by enhancing lipid rafts and immunosuppressive functions. There were also indications that cholesterol levels may have prognostic indications and that statins may have therapeutic benefits.
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There is a critical need for physiologically relevant, robust, and ready-to-use in vitro cellular assay platforms to rapidly model the infectivity of emerging viruses and develop new antiviral treatments. Here we describe the cellular complexity of human alveolar and tracheobronchial air liquid interface (ALI) tissue models during SARS-CoV-2 and influenza A virus (IAV) infections. Our results showed that both SARS-CoV-2 and IAV effectively infect these ALI tissues, with SARS-CoV-2 exhibiting a slower replication peaking at later time-points compared to IAV. We detected tissue-specific chemokine and cytokine storms in response to viral infection, including well-defined biomarkers in severe SARS-CoV-2 and IAV infections such as CXCL10, IL-6, and IL-10. Our single-cell RNA sequencing analysis showed similar findings to that found in vivo for SARS-CoV-2 infection, including dampened IFN response, increased chemokine induction, and inhibition of MHC Class I presentation not observed for IAV infected tissues. Finally, we demonstrate the pharmacological validity of these ALI tissue models as antiviral drug screening assay platforms, with the potential to be easily adapted to include other cell types and increase the throughput to test relevant pathogens.
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Tratamento Farmacológico da COVID-19 , Vírus da Influenza A , Influenza Humana , Antivirais/farmacologia , Antivirais/uso terapêutico , Quimiocinas , Epitélio , Humanos , Vírus da Influenza A/fisiologia , Influenza Humana/tratamento farmacológico , Pulmão , SARS-CoV-2 , Replicação ViralRESUMO
High severity fire may promote or reduce plant understory diversity in forests. However, few empirical studies have tested long-standing theoretical predictions that productivity may help to explain observed variation in post-fire plant diversity. Support for the influence of productivity on disturbance-diversity relationships is found predominantly in experimental grasslands, while tests over large areas with natural disturbance and productivity gradients are few and have yielded inconsistent results. Here, we measured the response of post-fire understory plant diversity to natural gradients of fire severity and productivity in a large-scale observational study in California's subalpine forests. We found that plant species richness increased with increasing fire severity and that this trend was stronger at high productivity. We used plant traits to investigate whether release from competition might contribute to increasing diversity and found that short-lived and far-dispersing species benefited more from high severity fire than their long-lived and near-dispersing counterparts. For far-dispersing species only, the benefit from high severity fire was stronger in high productivity plots where unburned species richness was lowest. Our results support theoretical connections between fire severity, productivity and plant communities that are key to predicting the consequences of increasing fire severity and frequency on diversity in the coming decades.