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A significant warming effect on arctic tundra is greening. Although this increase in predominantly woody vegetation has been linked to increases in gross primary productivity, increasing temperatures also stimulate ecosystem respiration. We present a novel analysis from small-scale plot measurements showing that the shape of the temperature- and light-dependent sink-to-source threshold (where net ecosystem exchange (NEE) equals zero) differs between two tussock tundra ecosystems differing in leaf area index (LAI). At the higher LAI site, the threshold is exceeded (i.e the ecosystem becomes a source) at relatively higher temperatures under low light but at lower temperatures under high light. At the lower LAI site, the threshold is exceeded at relatively lower temperatures under low light but at higher temperatures under high light. We confirmed this response at a single site where LAI was experimentally increased. This suggests the carbon balance of the tundra may be sensitive to small increases in temperature under low light, but that this effect may be significantly offset by increases in LAI. Importantly, we found that this LAI effect is reversed under high light, and so in a warming tundra, greater vegetation cover could have a progressively negative effect on net carbon uptake.
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Luz , Temperatura , Tundra , Regiões Árticas , Sequestro de Carbono , Carbono/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Ecossistema , Mudança ClimáticaRESUMO
OBJECTIVES: Provide an overview of the methods used to estimate the cost of sports-related injury published to date, and to highlight considerations and opportunities for future research. DESIGN: Scoping review. METHODS: Scopus, MEDLINE and CINHAL were searched from 1st January 2000 to 1st January 2023. Studies were screened by two independent reviewers and were eligible if they reported on a cost analysis or cost estimation of sports related injury. RESULTS: Thirty-one studies fulfilled the inclusion criteria. Twenty-seven studies (87â¯%) were published since 2014. The type of costs included direct healthcare costs (12 studies), indirect costs (10 studies) and a combination of both (9 studies). Twenty-one studies (68â¯%) used a bottom-up costing approach to measure costs of sports injury and estimated direct costs from the service rates or fee schedules of health systems, hospital, insurance companies or national insurance boards. A top-down approach was used in seven studies (23â¯%) to estimate the indirect salary cost of time-loss injuries using data from publicly available resources. Ten studies were from the cost perspective of a sporting organisation (32â¯%). There was a lack of explicit reporting of the costing method used and the perspective of those bearing the costs. CONCLUSIONS: Estimating the cost of sports injuries is an emerging area of research, with publications increasing in recent years. However, there remains a lack of methodological guidance to inform or appraise these studies. The expansion of established cost of illness checklists with sport injury explanations to guide future cost of sports injury studies is recommended.
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Traumatismos em Atletas , Custos de Cuidados de Saúde , Humanos , Traumatismos em Atletas/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Efeitos Psicossociais da Doença , Custos e Análise de CustoRESUMO
PURPOSE: The use of lung protective ventilation (LPV) during general anesthesia is an effective strategy among certified registered nurse anesthetists (CRNAs) to reduce and prevent the incidence of postoperative pulmonary complications. The purpose of this project was to implement a LPV protocol, assess CRNA provider adherence, and investigate differences in ventilation parameters and postoperative oxygen requirements. DESIGN: This quality improvement project was conducted using a pre- and postimplementation design. METHODS: Sixty patients undergoing robotic laparoscopic abdominal surgery and 35 CRNAs at a community hospital participated. An evidence-based intraoperative LPV protocol was developed, CRNA education was provided, and the protocol was implemented. Pre- and postimplementation, CRNA knowledge, and confidence were assessed. Ventilation data were collected at 1-minute intervals intraoperatively and oxygen requirements were recorded in the postanesthesia care unit (PACU). FINDINGS: Use of intraoperative LPV strategies increased 2.4%. Overall CRNA knowledge (P = .588), confidence (P = .031), and practice (P < .001) improved from pre- to postimplementation. Driving pressures decreased from pre- to postimplementation (P < .001). Supplemental oxygen use on admission to the PACU decreased from 93.3% to 70.0%. CONCLUSIONS: Educational interventions and implementation of a standardized protocol can improve the use of intraoperative LPV strategies and patient outcomes.
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Enfermeiros Anestesistas , Respiração Artificial , Humanos , RNA Complementar , Pulmão , Complicações Pós-Operatórias/prevenção & controle , OxigênioRESUMO
Spillover events of avian influenza A viruses (IAVs) to humans could represent the first step in a future pandemic1. Several factors that limit the transmission and replication of avian IAVs in mammals have been identified. There are several gaps in our understanding to predict which virus lineages are more likely to cross the species barrier and cause disease in humans1. Here, we identified human BTN3A3 (butyrophilin subfamily 3 member A3)2 as a potent inhibitor of avian IAVs but not human IAVs. We determined that BTN3A3 is expressed in human airways and its antiviral activity evolved in primates. We show that BTN3A3 restriction acts primarily at the early stages of the virus life cycle by inhibiting avian IAV RNA replication. We identified residue 313 in the viral nucleoprotein (NP) as the genetic determinant of BTN3A3 sensitivity (313F or, rarely, 313L in avian viruses) or evasion (313Y or 313V in human viruses). However, avian IAV serotypes, such as H7 and H9, that spilled over into humans also evade BTN3A3 restriction. In these cases, BTN3A3 evasion is due to substitutions (N, H or Q) in NP residue 52 that is adjacent to residue 313 in the NP structure3. Thus, sensitivity or resistance to BTN3A3 is another factor to consider in the risk assessment of the zoonotic potential of avian influenza viruses.
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Aves , Interações entre Hospedeiro e Microrganismos , Vírus da Influenza A , Influenza Aviária , Influenza Humana , Zoonoses Virais , Animais , Humanos , Aves/virologia , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/isolamento & purificação , Influenza Aviária/transmissão , Influenza Aviária/virologia , Influenza Humana/prevenção & controle , Influenza Humana/transmissão , Influenza Humana/virologia , Primatas , Sistema Respiratório/metabolismo , Sistema Respiratório/virologia , Medição de Risco , Zoonoses Virais/prevenção & controle , Zoonoses Virais/transmissão , Zoonoses Virais/virologia , Replicação ViralRESUMO
Coronavirus disease 2019 (COVID-19) is associated with adverse impacts in the cardiovascular system, but the mechanisms driving this response remain unclear. In this study, we conducted "pseudoviral infection" of SARS-CoV-2 subunits to evaluate their toxic effects in cardiomyocytes (CMs), that were derived from human induced pluripotent stem cells (hiPSCs). We found that the ectopic expression of S and ORF-9B subunits significantly impaired the contractile function and altered the metabolic profiles in human cardiomyocytes. Further mechanistic study has shown that the mitochondrial oxidative phosphorylation (OXPHOS), membrane potential, and ATP production were significantly decreased two days after the overexpression of S and ORF-9B subunits, while S subunits induced higher level of reactive oxygen species (ROS). Two weeks after overexpression, glycolysis was elevated in the ORF-9B group. Based on the transcriptomic analysis, both S and ORF-9B subunits dysregulated signaling pathways associated with metabolism and cardiomyopathy, including upregulated genes involved in HIF-signaling and downregulated genes involved in cholesterol biosynthetic processes. The ORF-9B subunit also enhanced glycolysis in the CMs. Our results collectively provide an insight into the molecular mechanisms underlying SARS-CoV-2 subunits-induced metabolic alterations and cardiac dysfunctions in the hearts of COVID-19 patients.
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Cannabis vaping involves the vaporization of a cannabis vaping liquid or solid via a vaping accessory such as a vape pen constructed of various metals or other parts. An increasing number of reports advocate for expansion of the testing and regulation of metal contaminants in cannabis vape liquids beyond the metals typically tested such as arsenic, cadmium, mercury, and lead to reflect the possibility of consumers' exposure to other metal contaminants. Metal contaminants may originate not only from the cannabis itself but also from the vape devices in which the cannabis vape liquid is packaged. However, metal analyses of cannabis vape liquids sampled from cannabis vaping devices are challenged by poor precision and reproducibility. Herein, we present data on the metal content of 12 metals in 20 legal and 21 illegal cannabis vape liquids. The lead mass fraction in several illegal samples reached up to 50 µg g-1. High levels of nickel (max 677 µg g-1) and zinc (max 426 µg g-1) were found in illegal samples, whereas the highest copper content (485 µg g-1) was measured in legal samples. Significant differences in metal mass fractions were observed in the legal cannabis vape liquid taken from two identical devices, even though the liquid was from the same lot of the same cannabis product. Metal particles in the vape liquids were observed by scanning electron microscopy, and laser ablation inductively coupled plasma mass spectrometry confirmed the presence of copper-, zinc-, lead-, and manganese-bearing particles, metals that are in common alloys that may be used to make vape devices. Colocalized particles containing aluminum, silica, and sodium were also detected. These results suggest that metal particles could be a contributing factor to poor measurement precision and for the first time, to the best of our knowledge, provide evidence of metal particles in cannabis vape liquids contained in unused cannabis vape pens.
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Thin-film photovoltaic cells using Cu2ZnSnS4 (CZTS, p-type) have many advantages, such as high photoconversion, low cost, and great tunability with earth-abundant, nontoxic elements, all of which are necessary to be long-term contributors to next-generation solar energy harvesting. Accurate measurements of bonding and band structures of both the thin-film materials and their interfaces are paramount to designing the solar devices layer-by-layer. Here, finely tuned 1 µm thick CZTS films, 50 nm thick CdS layers (n-type), and their 1 µm/2 nm p-n junction were fabricated inexpensively using our previously studied methods and investigated extensively for maximizing the key interface in the CZTS solar devices. Synthesized bulk CZTS and CdS were analyzed for structural deviations and crystal defects using synchrotron-based (SR) X-ray absorption fine structure (XAFS) along with simulated XAFS patterns. The structural properties of the two materials were designed to favor photovoltaic activity. Interface valence band structures of the CZTS/CdS p-n junction were measured through SR X-ray photoelectron spectroscopy (SR-XPS) and compared with the ones simulated using density functional theory. A full band diagram was constructed from XPS of the bulk films and SR-XPS of the interface, providing guidelines in optimizing charge-carrier extraction from the CZTS absorber to CdS buffer layer. It turns out that a small spike-like interface in the conduction band overlap was formed, maintaining a strong internal bias, while favoring a small energy barrier to prevent large-scale recombination from occurring. A large open-circuit voltage was obtained in the preliminary solar cell devices built on the small spike-like interface.
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This Review provides an overview of the emerging concepts of catalysts, membranes, and membrane electrode assemblies (MEAs) for water electrolyzers with anion-exchange membranes (AEMs), also known as zero-gap alkaline water electrolyzers. Much of the recent progress is due to improvements in materials chemistry, MEA designs, and optimized operation conditions. Research on anion-exchange polymers (AEPs) has focused on the cationic head/backbone/side-chain structures and key properties such as ionic conductivity and alkaline stability. Several approaches, such as cross-linking, microphase, and organic/inorganic composites, have been proposed to improve the anion-exchange performance and the chemical and mechanical stability of AEMs. Numerous AEMs now exceed values of 0.1 S/cm (at 60-80 °C), although the stability specifically at temperatures exceeding 60 °C needs further enhancement. The oxygen evolution reaction (OER) is still a limiting factor. An analysis of thin-layer OER data suggests that NiFe-type catalysts have the highest activity. There is debate on the active-site mechanism of the NiFe catalysts, and their long-term stability needs to be understood. Addition of Co to NiFe increases the conductivity of these catalysts. The same analysis for the hydrogen evolution reaction (HER) shows carbon-supported Pt to be dominating, although PtNi alloys and clusters of Ni(OH)2 on Pt show competitive activities. Recent advances in forming and embedding well-dispersed Ru nanoparticles on functionalized high-surface-area carbon supports show promising HER activities. However, the stability of these catalysts under actual AEMWE operating conditions needs to be proven. The field is advancing rapidly but could benefit through the adaptation of new in situ techniques, standardized evaluation protocols for AEMWE conditions, and innovative catalyst-structure designs. Nevertheless, single AEM water electrolyzer cells have been operated for several thousand hours at temperatures and current densities as high as 60 °C and 1 A/cm2, respectively.
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BACKGROUND: COVID-19 influenced education delivery worldwide. The Up the Hill Project (UTHP), a university mentoring program in Australia for people with intellectual disability, transitioned from a face-to-face to online format during 2020. RESULTS: The experience of transitioning online for one semester (12-week period) had positives and challenges associated with it. The UTHP Coordinator reported initial doubts for the online mode and identified the importance of at home support. However, the experience has opened up avenues for future program practices, such as intake processes and increased flexibility. From the participants' perspective, the online experience supported participants to develop new technology skills. However, challenges were that participants needed support, and missed face-to-face contact. CONCLUSION: Online mentoring in the UTHP had challenges, but has also supported continuation of university programs. Lessons learnt will influence the development of the UTHP in some capacity into the future.
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COVID-19 , Deficiência Intelectual , Tutoria , Adulto , Humanos , Universidades , MentoresRESUMO
Masting, the synchronous, highly variable flowering across years by a population of perennial plants, has been reported to be precipitated by various factors including nitrogen levels, drought conditions, and spring and summer temperatures. However, the molecular mechanism leading to the initiation of flowering in masting plants in particular years remains largely unknown, despite the potential impact of climate change on masting phenology. We studied genes controlling flowering in the alpine snow tussock Chionochloa pallens (Poaceae), a strongly masting perennial grass. We used a range of in situ and manipulated plants to obtain leaf samples from tillers (shoots) which subsequently remained vegetative or flowered. Here, we show that a novel orthologue of TERMINAL FLOWER 1 (TFL1; normally a repressor of flowering in other species) promotes the induction of flowering in C. pallens (hence Anti-TFL1), a conclusion supported by structural, functional and expression analyses. Global transcriptomic analysis indicated differential expression of CpTPS1, CpGA20ox1, CpREF6 and CpHDA6, emphasizing the role of endogenous cues and epigenetic regulation in terms of responsiveness of plants to initiate flowering. Our molecular-based study provides insights into the cellular mechanism of flowering in masting plants and will supplement ecological and statistical models to predict how masting will respond to global climate change.
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Poaceae , Neve , Mudança Climática , Epigênese Genética , Flores/genética , Regulação da Expressão Gênica de Plantas , Poaceae/genéticaRESUMO
Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that 2'-5'-oligoadenylate synthetase 1 (OAS1), through ribonuclease L, potently inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We show that a common splice-acceptor single-nucleotide polymorphism (Rs10774671) governs whether patients express prenylated OAS1 isoforms that are membrane-associated and sense-specific regions of SARS-CoV-2 RNAs or if they only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. In hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting that this antiviral defense is a major component of a protective antiviral response.
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2',5'-Oligoadenilato Sintetase/genética , 2',5'-Oligoadenilato Sintetase/metabolismo , COVID-19/genética , COVID-19/fisiopatologia , RNA de Cadeia Dupla/metabolismo , RNA Viral/metabolismo , SARS-CoV-2/fisiologia , Regiões 5' não Traduzidas , Células A549 , Animais , COVID-19/enzimologia , COVID-19/imunologia , Quirópteros/genética , Quirópteros/virologia , Coronaviridae/enzimologia , Coronaviridae/genética , Coronaviridae/fisiologia , Endorribonucleases/metabolismo , Humanos , Interferons/imunologia , Isoenzimas/genética , Isoenzimas/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Polimorfismo de Nucleotídeo Único , Prenilação de Proteína , RNA de Cadeia Dupla/química , RNA de Cadeia Dupla/genética , RNA Viral/química , RNA Viral/genética , Retroelementos , SARS-CoV-2/genética , Índice de Gravidade de Doença , Replicação ViralRESUMO
Remdesivir (RDV), a broadly acting nucleoside analogue, is the only FDA approved small molecule antiviral for the treatment of COVID-19 patients. To date, there are no reports identifying SARS-CoV-2 RDV resistance in patients, animal models or in vitro. Here, we selected drug-resistant viral populations by serially passaging SARS-CoV-2 in vitro in the presence of RDV. Using high throughput sequencing, we identified a single mutation in RNA-dependent RNA polymerase (NSP12) at a residue conserved among all coronaviruses in two independently evolved populations displaying decreased RDV sensitivity. Introduction of the NSP12 E802D mutation into our SARS-CoV-2 reverse genetics backbone confirmed its role in decreasing RDV sensitivity in vitro. Substitution of E802 did not affect viral replication or activity of an alternate nucleoside analogue (EIDD2801) but did affect virus fitness in a competition assay. Analysis of the globally circulating SARS-CoV-2 variants (>800,000 sequences) showed no evidence of widespread transmission of RDV-resistant mutants. Surprisingly, we observed an excess of substitutions in spike at corresponding sites identified in the emerging SARS-CoV-2 variants of concern (i.e., H69, E484, N501, H655) indicating that they can arise in vitro in the absence of immune selection. The identification and characterisation of a drug resistant signature within the SARS-CoV-2 genome has implications for clinical management and virus surveillance.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , RNA-Polimerase RNA-Dependente de Coronavírus/genética , Resistência Microbiana a Medicamentos/genética , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Animais , Evolução Biológica , Chlorocebus aethiops , Humanos , Mutação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Células VeroRESUMO
Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.
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Fosfatos de Dinucleosídeos , Fatores Reguladores de Interferon/genética , RNA Viral , Proteínas de Ligação a RNA/metabolismo , Células A549 , Linhagem Celular , Humanos , Interferon beta/farmacologia , RNA Mensageiro , Proteínas de Ligação a RNA/genética , Fenômenos Fisiológicos Virais , VírusRESUMO
Polydnaviruses are dsDNA viruses associated with endoparasitoid wasps. Delivery of the virus during parasitization of a caterpillar and subsequent virus gene expression is required for production of an amenable environment for parasitoid offspring development. Consequently, understanding of Polydnavirus gene function provides insight into mechanisms of host susceptibility and parasitoid wasp host range. Polydnavirus genes predominantly are arranged in multimember gene families, one of which is the vinnexins, which are virus homologues of insect gap junction genes, the innexins. Previous studies of Campoletis sonorensis Ichnovirus Vinnexins using various heterologous systems have suggested the four encoded members may provide different functionality in the infected caterpillar host. Here, we expressed two of the members, vnxG and vnxQ2, using recombinant baculoviruses in susceptible host, the caterpillar Heliothis virescens. Following intrahemocoelic injections, we observed that >90% of hemocytes (blood cells) were infected, producing recombinant protein. Larvae infected with a vinnexin-recombinant baculovirus exhibited significantly reduced molting rates relative to larvae infected with a control recombinant baculovirus and mock-infected larvae. Similarly, larvae infected with vinnexin-recombinant baculoviruses were less likely to survive relative to controls and showed reduced ability to encapsulate chromatography beads in an immune assay. In most assays, the VnxG protein was associated with more severe pathology than VnxQ2. Our findings support a role for Vinnexins in CsIV and more broadly Ichnovirus pathology in infected lepidopteran hosts, particularly in disrupting multicellular developmental and immune physiology.
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Baculoviridae/genética , Interações entre Hospedeiro e Microrganismos , Larva/crescimento & desenvolvimento , Mariposas/virologia , Polydnaviridae/genética , Proteínas Virais/genética , Animais , Encapsulamento de Células , Hemócitos/virologia , Larva/virologia , Polydnaviridae/metabolismo , Proteínas RecombinantesRESUMO
Mast flowering (or masting) is synchronous, highly variable flowering among years in populations of perennial plants. Despite having widespread consequences for seed consumers, endangered fauna and human health, masting is hard to predict. While observational studies show links to various weather patterns in different plant species, the mechanism(s) underpinning the regulation of masting is still not fully explained. We studied floral induction in Celmisia lyallii (Asteraceae), a mast flowering herbaceous alpine perennial, comparing gene expression in flowering and nonflowering plants. We performed translocation experiments to induce the floral transition in C. lyallii plants followed by both global and targeted expression analysis of flowering-pathway genes. Differential expression analysis showed elevated expression of ClSOC1 and ClmiR172 (promoters of flowering) in leaves of plants that subsequently flowered, in contrast to elevated expression of ClAFT and ClTOE1 (repressors of flowering) in leaves of plants that did not flower. The warm summer conditions that promoted flowering led to differential regulation of age and hormonal pathway genes, including ClmiR172 and ClGA20ox2, known to repress the expression of floral repressors and permit flowering. Upregulated expression of epigenetic modifiers of floral promoters also suggests that plants may maintain a novel "summer memory" across years to induce flowering. These results provide a basic mechanistic understanding of floral induction in masting plants and evidence of their ability to imprint various environmental cues to synchronize flowering, allowing us to better predict masting events under climate change.
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Asteraceae , Asteraceae/genética , Mudança Climática , Flores/genética , Regulação da Expressão Gênica de Plantas , Humanos , Folhas de Planta , SementesRESUMO
The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science.
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Vacinas contra COVID-19 , COVID-19/diagnóstico , COVID-19/virologia , Genética Reversa , SARS-CoV-2/genética , Células A549 , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , Chlorocebus aethiops , Códon , Humanos , Hidrazonas/farmacologia , Camundongos , Morfolinas/farmacologia , Fases de Leitura Aberta , Plasmídeos/genética , Pirimidinas/farmacologia , Serina Endopeptidases/metabolismo , Células Vero , Proteínas Virais/metabolismoRESUMO
COVID-19 is caused by a novel coronavirus called severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Virus cell entry is mediated through a protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S-protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in-vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S-protein RBD binding and prevent virus internalization.
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Short-term temperature response curves of leaf dark respiration (R-T) provide insights into a critical process that influences plant net carbon exchange. This includes how respiratory traits acclimate to sustained changes in the environment. Our study analysed 860 high-resolution R-T (10-70°C range) curves for: (a) 62 evergreen species measured in two contrasting seasons across several field sites/biomes; and (b) 21 species (subset of those sampled in the field) grown in glasshouses at 20°C : 15°C, 25°C : 20°C and 30°C : 25°C, day : night. In the field, across all sites/seasons, variations in R25 (measured at 25°C) and the leaf T where R reached its maximum (Tmax ) were explained by growth T (mean air-T of 30-d before measurement), solar irradiance and vapour pressure deficit, with growth T having the strongest influence. R25 decreased and Tmax increased with rising growth T across all sites and seasons with the single exception of winter at the cool-temperate rainforest site where irradiance was low. The glasshouse study confirmed that R25 and Tmax thermally acclimated. Collectively, the results suggest: (1) thermal acclimation of leaf R is common in most biomes; and (2) the high T threshold of respiration dynamically adjusts upward when plants are challenged with warmer and hotter climates.
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Aclimatação , Folhas de Planta , Ecossistema , Respiração , TemperaturaRESUMO
Motor neuron degeneration and spinal cord demyelination are hallmark pathological events in Amyotrophic Lateral Sclerosis (ALS). Endogenous retrovirus-K (ERVK) expression has an established association with ALS neuropathology, with murine modeling pointing to a role for the ERVK envelope (env) gene in disease processes. Here, we describe a novel viral protein cryptically encoded within the ERVK env transcript, which resembles two distinct cysteine-rich neurotoxic proteins: conotoxin proteins found in marine snails and the Human Immunodeficiency Virus (HIV) Tat protein. Consistent with Nuclear factor-kappa B (NF-κB)-induced retrotransposon expression, the ERVK conotoxin-like protein (CTXLP) is induced by inflammatory signaling. CTXLP is found in the nucleus, impacting innate immune gene expression and NF-κB p65 activity. Using human autopsy specimens from patients with ALS, we further showcase CTXLP expression in degenerating motor cortex and spinal cord tissues, concomitant with inflammation linked pathways, including enhancement of necroptosis marker mixed lineage kinase domain-like (MLKL) protein and oligodendrocyte maturation/myelination inhibitor Nogo-A. These findings identify CTXLP as a novel ERVK protein product, which may act as an effector in ALS neuropathology.
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Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/genética , Animais , Conotoxinas/genética , Conotoxinas/metabolismo , Retrovirus Endógenos/metabolismo , Retrovirus Endógenos/patogenicidade , Humanos , NF-kappa B/metabolismo , Necroptose/genética , Necroptose/fisiologia , Retroviridae/genética , Retroviridae/patogenicidadeRESUMO
BACKGROUND: Mast flowering ('masting') is characterized by mass synchronized flowering at irregular intervals in populations of perennial plants over a wide geographical area, resulting in irregular high seed production. While masting is a global phenomenon, it is particularly prevalent in the alpine flora of New Zealand. Increases in global temperature may alter the masting pattern, affecting wider communities with a potential impact on plant-pollinator interactions, seed set and food availability for seed-consuming species. SCOPE: This review summarizes an ecological temperature model (ΔT) that is being used to predict the intensity of a masting season. We introduce current molecular studies on flowering and the concept of an 'epigenetic summer memory' as a driver of mast flowering. We propose a hypothetical model based on temperature-associated epigenetic modifications of the floral integrator genes FLOWERING LOCUS T, FLOWERING LOCUS C and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1. CONCLUSIONS: Genome-wide transcriptomic and targeted gene expression analyses are needed to establish the developmental and physiological processes associated with masting. Such analyses may identify changes in gene expression that can be used to predict the intensity of a forthcoming masting season, as well as to determine the extent to which climate change will influence the mass synchronized flowering of masting species, with downstream impacts on their associated communities.