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Nearly all adhesives1,2 are derived from petroleum, create permanent bonds3, frustrate materials separation for recycling4,5 and prevent degradation in landfills. When trying to shift from petroleum feedstocks to a sustainable materials ecosystem, available options suffer from low performance, high cost or lack of availability at the required scales. Here we present a sustainably sourced adhesive system, made from epoxidized soy oil, malic acid and tannic acid, with performance comparable to that of current industrial products. Joints can be cured under conditions ranging from use of a hair dryer for 5 min to an oven at 180 °C for 24 h. Adhesion between metal substrates up to around 18 MPa is achieved, and, in the best cases, performance exceeds that of a classic epoxy, the strongest modern adhesive. All components are biomass derived, low cost and already available in large quantities. Manufacturing at scale can be a simple matter of mixing and heating, suggesting that this new adhesive may contribute towards the sustainable bonding of materials.
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Stalled DNA replication fork restart after stress as orchestrated by ATR kinase, BLM helicase, and structure-specific nucleases enables replication, cell survival, and genome stability. Here we unveil human exonuclease V (EXO5) as an ATR-regulated DNA structure-specific nuclease and BLM partner for replication fork restart. We find that elevated EXO5 in tumors correlates with increased mutation loads and poor patient survival, suggesting that EXO5 upregulation has oncogenic potential. Structural, mechanistic, and mutational analyses of EXO5 and EXO5-DNA complexes reveal a single-stranded DNA binding channel with an adjacent ATR phosphorylation motif (T88Q89) that regulates EXO5 nuclease activity and BLM binding identified by mass spectrometric analysis. EXO5 phospho-mimetic mutant rescues the restart defect from EXO5 depletion that decreases fork progression, DNA damage repair, and cell survival. EXO5 depletion furthermore rescues survival of FANCA-deficient cells and indicates EXO5 functions epistatically with SMARCAL1 and BLM. Thus, an EXO5 axis connects ATR and BLM in directing replication fork restart.
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Proteínas Mutadas de Ataxia Telangiectasia/genética , Replicação do DNA/genética , DNA/genética , Exonucleases/genética , Instabilidade Genômica/genética , RecQ Helicases/genética , Linhagem Celular , Linhagem Celular Tumoral , Dano ao DNA/genética , DNA Helicases/genética , Análise Mutacional de DNA/métodos , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Células HEK293 , Células HeLa , Humanos , Mutação/genética , Oncogenes/genética , Fosforilação/genética , Regulação para Cima/genéticaRESUMO
PURPOSE: Artificial Intelligence (AI) has become increasingly integrated clinically within neurosurgical oncology. This report reviews the cutting-edge technologies impacting tumor treatment and outcomes. METHODS: A rigorous literature search was performed with the aid of a research librarian to identify key articles referencing AI and related topics (machine learning (ML), computer vision (CV), augmented reality (AR), virtual reality (VR), etc.) for neurosurgical care of brain or spinal tumors. RESULTS: Treatment of central nervous system (CNS) tumors is being improved through advances across AI-such as AL, CV, and AR/VR. AI aided diagnostic and prognostication tools can influence pre-operative patient experience, while automated tumor segmentation and total resection predictions aid surgical planning. Novel intra-operative tools can rapidly provide histopathologic tumor classification to streamline treatment strategies. Post-operative video analysis, paired with rich surgical simulations, can enhance training feedback and regimens. CONCLUSION: While limited generalizability, bias, and patient data security are current concerns, the advent of federated learning, along with growing data consortiums, provides an avenue for increasingly safe, powerful, and effective AI platforms in the future.
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Inteligência Artificial , Procedimentos Neurocirúrgicos , Humanos , Procedimentos Neurocirúrgicos/métodos , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Oncologia/métodos , Neoplasias do Sistema Nervoso Central/cirurgia , Neurocirurgia/métodosRESUMO
Recent work in combustion and atmospheric chemistry has revealed cases in which diastereomers must be distinguished to accurately model a reacting flow. This paper presents an open-source framework for introducing such stereoisomer resolution into a kinetic mechanism. We detail our definitions and algorithms for labeling and enumerating the stereoisomers of a molecule and then generalize our system to describe the transition state (TS) of a reaction. This allows for the stereospecific enumeration of reactants and products while accounting for "fleeting" stereochemistry that is unique to the TS. We also present the AutoMech Chemical Identifier (AMChI), an InChI-like string identifier that accounts for stereocenters omitted by InChI. This identifier is extended to describe the TSs of reactions, providing a universal lookup key for specific reaction channels. The final piece of our methodology is an analytic formula to remove redundancy from a stereoresolved mechanism when its enantiomers exist as a racemic mixture, making it as compact as possible while fully accounting for the differences between diastereomers. In applying our methodology to two subsets of the NUIGMech1.1 mechanism, we find that our approach reduces the extra species added for large-fuel oxidation from 2231 (133%, full expansion) to 694 (41%, nonredundant expansion). We also find that for pyrolysis more than a quarter of the species in the expanded mechanism cannot be properly described by an InChI string, requiring an AMChI string to communicate their identity. Finally, we find that roughly one-quarter of the large-fuel oxidation reactions and one-third of the pyrolysis reactions include fleeting TS stereochemistry, which may have relevant effects on their kinetics.
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Recent modeling studies of ammonia oxidation, which are motivated by the prospective role of ammonia as a zero-carbon fuel, have indicated significant discrepancies among the existing literature mechanisms. In this study, high-level theoretical kinetics predictions have been obtained for reactions on the NH2O potential energy surface, including the NH2 + O, HNO + H, and NH + OH reactions. These reactions have previously been highlighted as important reactions in NH3 oxidation with high sensitivity and high uncertainty. The potential energy surface is explored with coupled cluster calculations, including large basis sets and high-level corrections to yield high-accuracy (â¼0.2 kcal/mol 2σ uncertainty) estimates of the stationary point energies. Variational transition state theory is used to predict the microcanonical rate constants, which are then incorporated in master equation treatments of the temperature- and pressure-dependent kinetics. For radical-radical channels, the microcanonical rates are obtained from variable reaction coordinate transition state theory implementing directly evaluated multireference electronic energies. The analysis yields predictions for the total rate constants as well as the branching ratios. We find that the NO + H2 channel contributes 10% of the total NH2 + O flux at combustion temperatures, although this channel is not included in modern NH3 oxidation mechanisms. Modeling is used to illustrate the ramifications of these rate predictions on the kinetics of NH3 oxidation and NOx formation. The present results for NH2 + O are important for predicting the chain branching and formation of NO in the oxidation of NH3 and thermal DeNOx.
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The kinetics of peroxy radical (RO2) reactions have been of long-standing interest in atmospheric and combustion chemistry. Nevertheless, the lack of kinetic studies at higher temperatures for their reactions with other radicals such as OH has precluded the inclusion of this class of reactions in detailed kinetics models developed for combustion applications. In this work, guided by the limited room-temperature experimental studies on selected alkyl-peroxy radicals and literature theoretical kinetics on the prototypical CH3O2 + OH system, we have performed parametric studies on the effect of uncertainties in the rate coefficients and branching ratios to potential product channels for RO2 + OH reactions at higher temperatures. Literature kinetics models were used to simulate autoignition delays, laminar flame speeds, and speciation profiles in flow and stirred reactors for a variety of common combustion-relevant fuels. Inclusion of RO2 + OH reactions was found to retard autoignition in fuel-lean (φ = 0.5) mixtures of ethane and dimethyl ether in air. The observed effects were noticeably more pronounced in ozone-enriched combustion of ethane and dimethyl ether. The simulations also examined the influence of ozone doping levels, pressures, and equivalence ratios for both ethane and dimethyl ether oxidation. Sensitivity and flux analyses revealed that the RO2 + OH reaction is a significant sink of RO2 radicals at the early stage of autoignition, affecting fuel oxidation through RO2 â QOOH, RO2 â alkene + HO2, or RO2 + HO2 â ROOH + O2. Additionally, the kinetic stability of the trioxide formed from RO2 + OH reactions was investigated using master equation analyses. Last, we discuss other bimolecular reactions that are missing in literature kinetics models but are relevant to hydrocarbon oxidation initiated by external radical sources (plasma-enhanced, ozone-enriched combustion, etc.). The present simulations provide a strong motivation for better characterizing the bimolecular kinetics of peroxy radicals.
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Quantitative descriptions of non-adiabatic transition rates at intermediate temperatures are challenging due to the simultaneous importance of quantum and anharmonic effects. In this paper, the interplay between quantum effects-for motion across or along the seam of crossing-and anharmonicity in the seam potential is considered within the weak coupling limit. The well-known expression for quantized 1-D motion across the seam (i.e., tunneling) in the linear terms approximation is derived in the thermal domain using the Lagrangian formalism, which is then applied to the case when tunneling is distributed along the seam of crossing (treating motion along the seam classically). For high-frequency quantum modes, a vibrationally adiabatic (VA) approach is developed that introduces to the non-adiabatic rate constant a factor associated with high-frequency wavefunction overlap; this approach treats the high-frequency motion along the seam quantum mechanically. To test these methodologies, the reaction N2O â N2 + O(3P) was chosen. CCSD(T)-F12b/cc-pVTZ-F12 explorations of the 3A'-1A' seam of N2O revealed that seam anharmonicity has a strong effect on the rate constant (a factor of â¼20 at 2000 K). Several quantum effects were found to be significant at intermediate/lower temperatures, including the quantum N-N vibration that was coupled with seam anharmonicity using the VA approach. Finally, a 1-D approximation to non-adiabatic instanton theory is presented to estimate the validity limit of the linear terms model at low temperatures (â¼250 K for N2O). We recommend that the assumptions built into many statistical theories for non-adiabatic reactions-harmonic behavior, classical motion, linear terms, and weak coupling-should be verified on a case-by-case basis.
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The accurate repair of genomic damage mediated by ionizing radiation (IR), chemo- or radiomimetic drugs, or other exogenous agents, is necessary for maintenance of genome integrity, preservation of cellular viability and prevention of oncogenic transformation. Eukaryotes have conserved mechanisms designed to perceive and repair the damaged DNA quite efficiently. Among the different types of DNA damage, double strand breaks (DSB) are the most detrimental. The cellular DNA DSB response is a hierarchical signaling network that integrates damage sensing and repair with chromatin structural changes that involve a range of pre-existing and induced covalent modifications. Recent studies have revealed that pre-existing histone modifications are important contributors within this signaling/repair network. This chapter discusses the role of a critical histone acetyl transferase (HAT) known as MOF (males absent on the first) and the histone deacetylases (HDACs) Sirtuins on histone H4K16 acetylation (H4K16ac) and DNA damage repair. We also discuss the role of this important histone modification in light of metabolic rewiring and its role in regulating human pathophysiologic states.
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Envelhecimento , Histona Acetiltransferases , Neoplasias , Sirtuínas , Humanos , Acetilação , Cromatina , DNA/metabolismo , Dano ao DNA , Reparo do DNA , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Histonas/metabolismo , Neoplasias/genética , Sirtuínas/genética , Sirtuínas/metabolismoRESUMO
As the most common setting where youth access behavioral healthcare, the education sector frequently employs training and follow-up consultation as cornerstone implementation strategies to promote the implementation of evidence-based practices (EBPs). However, these strategies alone are not sufficient to promote desirable implementation (e.g., intervention fidelity) and youth behavioral outcomes (e.g., mitigated externalizing behaviors). Theory-informed pragmatic pre-implementation enhancement strategies (PIES) are needed to prevent the lackluster outcomes of training and consultation. Specifically, social cognitive theory explicates principles that inform the design of PIES content and specify mechanisms of behavior change (e.g., "intentions to implement" (ITI)) to target increasing providers' responsiveness to training and consultation. This triple-blind parallel randomized controlled trial preliminarily examined the efficacy of a pragmatic PIES based on social cognitive theories (SC-PIES) to improve implementation and youth behavioral outcomes from universal preventive EBPs in the education sector. Teachers from a diverse urban district were recruited and randomly assigned to the treatment (SC-PIES; ntreatment = 22) or active control condition (administrative meeting; ncontrol = 21). Based on the condition assigned, teachers received the SC-PIES or met with administrators before their EBP training. We assessed teachers' ITI, intervention fidelity, and youth behavioral outcome (academic engagement as an incompatible behavior to externalizing disorders) at baseline, immediately after training, and 6 weeks afterward. A series of ANCOVAs detected sizeable effects of SC-PIES, where teachers who received SC-PIES demonstrated significantly larger improvement in their ITI, intervention fidelity, and youth behaviors as compared to the control. Conditional analyses indicated that teachers' ITI partially mediated the effect of SC-PIES on intervention fidelity, which in turn led to improved youth behaviors. Findings suggest that theory-informed pragmatic PIES targeting providers' ITI can boost their responsiveness to implementation strategies, as reflected in improved implementation behaviors and youth behavioral outcomes. The results have implications for targeting motivational mechanisms of behavior change and situating preventive implementation strategies at the intersection between the preparation and active implementation stages of an implementation process. Limitations and implications for research and practice are discussed. Clinicaltrials.gov: NCT05240222. Registered on: 2/14/2022. Retrospectively registered. https://clinicaltrials.gov/show/NCT05240222.
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Pessoal de Educação , Instituições Acadêmicas , Adolescente , Humanos , Prática Clínica Baseada em Evidências , Escolaridade , Encaminhamento e ConsultaRESUMO
Dimethyl ether (DME) oxidation is a model chemical system with a small number of prototypical reaction intermediates that also has practical importance for low-carbon transportation. Although it has been studied experimentally and theoretically, ambiguity remains in the relative importance of competing DME oxidation pathways in the low-temperature autoignition regime. To focus on the primary reactions in DME autoignition, we measured the time-resolved concentration of five intermediates, CH3OCH2OO (ROO), OOCH2OCH2OOH (OOQOOH), HOOCH2OCHO (hydroperoxymethyl formate, HPMF), CH2O, and CH3OCHO (methyl formate, MF), from photolytically initiated experiments. We performed these studies at P = 10 bar and T = 450-575 K, using a high-pressure photolysis reactor coupled to a time-of-flight mass spectrometer with tunable vacuum-ultraviolet synchrotron ionization at the Advanced Light Source. Our measurements reveal that the timescale of ROO decay and product formation is much shorter than predicted by current DME combustion models. The models also strongly underpredict the observed yields of CH2O and MF and do not capture the temperature dependence of OOQOOH and HPMF yields. Adding the ROO + OH â RO + HO2 reaction to the chemical mechanism (with a rate coefficient approximated from similar reactions) improves the prediction of MF. Increasing the rate coefficients of ROO â QOOH and QOOH + O2 â OOQOOH reactions brings the model predictions closer to experimental observations for OOQOOH and HPMF, while increasing the rate coefficient for the QOOH â 2CH2O + OH reaction is needed to improve the predictions of formaldehyde. To aid future quantification of DME oxidation intermediates by photoionization mass spectrometry, we report experimentally determined ionization cross-sections for ROO, OOQOOH, and HPMF.
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Heterochromatin protein 1ß (HP1ß), encoded by the Cbx1 gene, has been functionally linked to chromatin condensation, transcriptional regulation, and DNA damage repair. Here we report that testis-specific Cbx1 conditional knockout (Cbx1 cKO) impairs male germ cell development in mice. Depletion of HP1ß negatively affected sperm maturation and increased seminiferous tubule degeneration in Cbx1 cKO mice. In addition, the spermatogonia have elevated γ-H2AX foci levels as do Cbx1 deficient mouse embryonic fibroblasts (MEFs) as compared to wild-type (WT) control MEFs. The increase in γ-H2AX foci in proliferating Cbx1 cKO cells indicates defective replication-dependent DNA damage repair. Depletion or loss of HP1ß from human cells and MEFs increased DNA replication fork stalling and firing of new origins of replication, indicating defective DNA synthesis. Taken together, these results suggest that loss of HP1ß in proliferating cells leads to DNA replication defects with associated DNA damage that impact spermatogenesis.
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Proteínas Cromossômicas não Histona/genética , Replicação do DNA , Regulação da Expressão Gênica no Desenvolvimento , Espermatogênese/genética , Alelos , Animais , Apoptose/genética , Linhagem Celular , Homólogo 5 da Proteína Cromobox , Proteínas Cromossômicas não Histona/metabolismo , Replicação do DNA/efeitos dos fármacos , Imunofluorescência , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Marcação de Genes , Loci Gênicos , Histonas/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Knockout , Fenótipo , Maturação do Esperma/genética , Espermatogênese/efeitos dos fármacos , Espermatogônias/citologia , Espermatogônias/metabolismoRESUMO
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with debilitating arthralgia in humans. RNA secondary structure in the viral genome plays an important role in the lifecycle of alphaviruses; however, the specific role of RNA structure in regulating CHIKV replication is poorly understood. Our previous studies found little conservation in RNA secondary structure between alphaviruses, and this structural divergence creates unique functional structures in specific alphavirus genomes. Therefore, to understand the impact of RNA structure on CHIKV biology, we used SHAPE-MaP to inform the modeling of RNA secondary structure throughout the genome of a CHIKV isolate from the 2013 Caribbean outbreak. We then analyzed regions of the genome with high levels of structural specificity to identify potentially functional RNA secondary structures and identified 23 regions within the CHIKV genome with higher than average structural stability, including four previously identified, functionally important CHIKV RNA structures. We also analyzed the RNA flexibility and secondary structures of multiple 3'UTR variants of CHIKV that are known to affect virus replication in mosquito cells. This analysis found several novel RNA structures within these 3'UTR variants. A duplication in the 3'UTR that enhances viral replication in mosquito cells led to an overall increase in the amount of unstructured RNA in the 3'UTR. This analysis demonstrates that the CHIKV genome contains a number of unique, specific RNA secondary structures and provides a strategy for testing these secondary structures for functional importance in CHIKV replication and pathogenesis.IMPORTANCE Chikungunya virus (CHIKV) is a mosquito-borne RNA virus that causes febrile illness and debilitating arthralgia in humans. CHIKV causes explosive outbreaks but there are no approved therapies to treat or prevent CHIKV infection. The CHIKV genome contains functional RNA secondary structures that are essential for proper virus replication. Since RNA secondary structures have only been defined for a small portion of the CHIKV genome, we used a chemical probing method to define the RNA secondary structures of CHIKV genomic RNA. We identified 23 highly specific structured regions of the genome, and confirmed the functional importance of one structure using mutagenesis. Furthermore, we defined the RNA secondary structure of three CHIKV 3'UTR variants that differ in their ability to replicate in mosquito cells. Our study highlights the complexity of the CHIKV genome and describes new systems for designing compensatory mutations to test the functional relevance of viral RNA secondary structures.
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Regiões 3' não Traduzidas/genética , Vírus Chikungunya/genética , RNA Viral/química , RNA Viral/genética , Animais , Linhagem Celular , Febre de Chikungunya/virologia , Chlorocebus aethiops , Culicidae , Efeito Citopatogênico Viral , Genoma Viral , Mutação , Conformação de Ácido Nucleico , Análise de Sequência , Células Vero , Replicação Viral/genéticaRESUMO
Diastereomers have historically been ignored when building kinetic mechanisms for combustion. Low-temperature oxidation kinetics, which continues to gain interest in both combustion and atmospheric communities, may be affected by the inclusion of diastereomers in radical chain-branching pathways. In this work, key intermediates and transition states lacking stereochemical specification in an existing diethyl ether low-temperature oxidation mechanism were replaced with their diastereomeric counterparts. Rate coefficients for reactions involving diastereomers were computed with ab initio transition state theory master equation calculations. The presence of diastereomers increased rate coefficients by factors of 1.2-1.6 across various temperatures and pressures. Ignition delay simulations incorporating these revised rate coefficients indicate that the diastereomers enhanced the overall reactivity of the mechanism by almost 15% and increased the peak ketohydroperoxide concentration by 30% in the negative temperature coefficient region at combustion-relevant pressures. These results provide an illustrative indication of the important role of stereomeric effects in oxidation kinetics.
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Training and consultation are core implementation strategies used to support the adoption and delivery of evidence-based prevention programs (EBPPs), but are often insufficient alone to effect teacher behavior change. Motivational interviewing (MI) and related behavior change techniques (e.g., strategic education, social influence, implementation planning) delivered in a group format offer promising supplements to training and consultation to improve EBPP implementation. Beliefs and Attitudes for Successful Implementation in Schools for Teachers (BASIS-T) is a theoretically informed, motivational implementation strategy delivered in a group format prior to and immediately after EBPP training. The purpose of this study was to examine the proximal effects of BASIS-T on hypothesized mechanisms of behavior change (e.g., attitudes, subjective norms, intentions to implement) in the context of teachers receiving training and consultation to implement the Good Behavior Game. As part of a pilot trial, 83 elementary school teachers from 9 public elementary schools were randomly assigned (at the school-level to reduce contamination across participants) to a BASIS-T (n = 44) or active comparison control (n = 39) condition, with both conditions receiving Good Behavior Game (GBG) training and consultation. A series of mixed effects models revealed meaningful effects favoring BASIS-T on a number of hypothesized mechanisms of behavior change leading to increased motivation to implement GBG. The implications, limitations, and directions for future research on the use of MI with groups of individuals and other behavior change techniques to increase the yield of training and consultation are discussed.
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Pessoal de Educação , Entrevista Motivacional , Humanos , Motivação , Professores Escolares , Instituições AcadêmicasRESUMO
BACKGROUND: Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines as well as the early identification of individuals with the highest risk that may require supportive treatment. METHODS: We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, severe acute respiratory syndrome-coronavirus, and West Nile virus. RESULTS: The CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality after infection and strains exhibiting no mortality. We then used comprehensive preinfection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection. CONCLUSIONS: These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.
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Mortalidade , Infecções por Vírus de RNA/imunologia , Infecções por Vírus de RNA/mortalidade , Animais , Camundongos de Cruzamento Colaborativo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Vírus da Influenza A/imunologia , Influenza Humana , Masculino , Camundongos , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/mortalidade , RNA , Infecções por Vírus de RNA/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/mortalidade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Vacinas Virais/imunologia , Febre do Nilo Ocidental/imunologia , Febre do Nilo Ocidental/mortalidade , Vírus do Nilo Ocidental/imunologiaRESUMO
Prion diseases are a group of incurable neurodegenerative disorders that affect humans and animals via infection with proteinaceous particles called prions. Prions are composed of PrPSc, a misfolded version of the cellular prion protein (PrPC). During disease progression, PrPSc replicates by interacting with PrPC and inducing its conversion to PrPSc As PrPSc accumulates, cellular stress mechanisms are activated to maintain cellular proteostasis, including increased protein chaperone levels. However, the exact roles of several of these chaperones remain unclear. Here, using various methodologies to monitor prion replication (i.e. protein misfolding cyclic amplification and cellular and animal infectivity bioassays), we studied the potential role of the molecular chaperone heat shock protein 70 (HSP70) in prion replication in vitro and in vivo Our results indicated that pharmacological induction of the heat shock response in cells chronically infected with prions significantly decreased PrPSc accumulation. We also found that HSP70 alters prion replication in vitro More importantly, prion infection of mice lacking the genes encoding stress-induced HSP70 exhibited accelerated prion disease progression compared with WT mice. In parallel with HSP70 being known to respond to endogenous and exogenous stressors such as heat, infection, toxicants, and ischemia, our results indicate that HSP70 may also play an important role in suppressing or delaying prion disease progression, opening opportunities for therapeutic intervention.
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Proteínas de Choque Térmico HSP70/metabolismo , Doenças Priônicas/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Progressão da Doença , Retículo Endoplasmático/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Priônicas/metabolismo , Príons/metabolismo , Dobramento de ProteínaRESUMO
Phosphine (PH3) is a highly reactive and toxic gas. Prior experimental investigations of PH3 pyrolysis reactions have included only low-temperature measurements. This study reports the first shock-tube measurements of PH3 pyrolysis using a new PH3 laser absorption technique near 4.56 µm. Experiments were conducted in mixtures of 0.5% PH3/Ar behind reflected shock waves at temperatures of 1460-2013 K and pressures of â¼1.3 and â¼0.5 atm. The PH3 time histories displayed two-stage behavior similar to that previously observed for NH3 decomposition, suggesting by analogy that the rate constant for PH3 + M â PH2 + H + M (R1) could be determined. A simple three-step mechanism was assembled for data analysis. In a detailed kinetic analysis of the first-stage PH3 decomposition, values of k1,0 were obtained and best described by (in cm3·mol-1·s-1) k1,0 = 7.78 × 1017 exp(-80,400/RT), with units of cal, mol, K, s, and cm3. Agreement between the 1.3 and 0.5 atm data confirmed that the measured k1,0 was in the low-pressure limit. Agreement of the experimental k1,0 with ab initio estimates resolved the question of the main pathway of PH3 decomposition: it proceeds as PH3 â PH2 + H instead of PH3 â PH + H2.
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The root lesion nematode Pratylenchus thornei causes economic losses in wheat and barley internationally through both reduced grain yield and grain quality. This study investigated the relationships between the presowing P. thornei density and grain yield and the postharvest nematode densities. Four field experiments were conducted at the same site between 2010 and 2014. A range of presowing P. thornei densities was established in the first year by growing three cereal cultivars that ranged from resistant to susceptible. In the following year, plots were sown with the five same cereal cultivars. A linear relationship was observed between the natural log of the presowing P. thornei density and grain yield across all seasons. The results showed that grain yield losses varied between cultivars and seasons. The importance of season was significant, with this study conducted over several seasons, and it highlighted the variability in yield losses between seasons, which will need further investigation. The greatest yield losses observed were 25 to 28% when the maximum presowing P. thornei densities ranged between 150 and 250 P. thornei g of soil-1. An analysis of the relationship between the presowing and postharvest nematode densities revealed that increased presowing nematode densities resulted in decreased multiplication rates in all seasons and in all cultivars. Nematode multiplication rates also varied between seasons. These results explain why it is difficult to predict nematode levels based on cropping history, and additionally, they highlight the importance of growing resistant cultivars to maintain low levels of P. thornei to minimize risk of yield losses.
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Hordeum , Tylenchoidea , Animais , Grão Comestível , Doenças das Plantas , TriticumRESUMO
The root lesion nematode (RLN) species Pratylenchus thornei and P. neglectus are widely distributed within cropping regions of Australia and have been shown to limit grain production. Field experiments conducted to compare the performance of cultivars in the presence of RLNs investigate management options for growers by identifying cultivars with resistance, by limiting nematode reproduction, and tolerance, by yielding well in the presence of nematodes. A novel experimental design approach for RLN experiments is proposed where the observed RLN density, measured prior to sowing, is used to condition the randomization of cultivars to field plots. This approach ensured that all cultivars were exposed to consistent ranges of RLN in order to derive valid assessments of relative cultivar tolerance and resistance. Using data from a field experiment designed using the conditioned randomization approach and conducted in Formartin, Australia, the analysis of tolerance and resistance was undertaken in a linear mixed model framework. Yield response curves were derived using a random regression approach and curves modeling change in RLN densities between sowing and harvest were derived using splines to account for nonlinearity. Groups of cultivars sharing similar resistance levels could be identified. A comparison of slopes of yield response curves of cultivars belonging to the same resistance class identified differing tolerance levels for cultivars with equivalent exposures to both presowing and postharvest RLN densities. As such, the proposed design and analysis approach allowed tolerance to be assessed independently of resistance.
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Triticum , Tylenchoidea , Animais , Austrália , Doenças das Plantas , Projetos de PesquisaRESUMO
OBJECTIVE: To assess the efficacy of a train-the-trainer model for sporting coaches delivering a youth sports-based resilience program. DESIGN: A quasi-experimental design was applied, with a pre-post comparison, utilising purposive sampling to take advantage of an existing naturally formed group. SETTING AND PARTICIPANTS: A total of 11 coaches and 86 athletes involved in a community rowing program. MAIN OUTCOME MEASURE(S): Coaches responded to paper-based measures of resilience and knowledge/attitudes pre- and post-completion of a training workshop. Athletes responded to online measures of stress, efficacy and life satisfaction pre- and post-completion of a resilience program. RESULTS: Following the completion of the train-the-trainer workshop, coaches reported significant increases in general knowledge and confidence in teaching resilience skills. Following the delivery of the resilience program, athlete self-efficacy and satisfaction with life scores were significantly higher, with significant reductions in reported stress for athletes trained by the varsity-level coaches. CONCLUSION: There is support for investing in a train-the-trainer model for the delivery of a resilience skills program within a sports context. Caution is given to investing in the training and support of the coaches, particularly coaches with less coaching experience. These results are consistent with previous research and demonstrate support for coach-led resilience programs being effective in community settings, with implications for rural and remote locations.