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Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes at the 3' position of the NS4 gene and used this pool as our viral inoculum for in vivo infections of different mouse lines. We found that over the course of persistent CR6 infection, shed virus was predominantly colon-derived, and viral barcode richness decreased over time irrespective of host immune status, suggesting that persistent infection involves a series of reinfection events. In mice lacking the IFN-λ receptor, intestinal barcode richness was enhanced, correlating with increased viral intestinal replication. IL-4 treatment, which increases tuft cell numbers, also increased barcode richness, indicating the abundance of permissive tuft cells to be a bottleneck during CR6 infection. In mice lacking type I IFN signaling (Ifnar1-/-) or all IFN signaling (Stat1-/-), barcode diversity at extraintestinal sites was dramatically increased, implicating different IFNs as critical bottlenecks at specific tissue sites. Of interest, extraintestinal barcodes were overlapping but distinct from intestinal barcodes, indicating that disseminated virus represents a distinct viral population than that replicating in the intestine. Barcoded viruses are a valuable tool to explore the influence of host factors on viral diversity in the context of establishment and maintenance of infection as well as dissemination and have provided important insights into how NoV infection proceeds in immunocompetent and immunocompromised hosts.
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Infecciones por Caliciviridae , Interferones , Norovirus , Animales , Norovirus/fisiología , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/inmunología , Ratones , Interferones/metabolismo , Infección Persistente/virología , Infección Persistente/inmunología , Ratones Endogámicos C57BL , Mucosa Intestinal/virología , Mucosa Intestinal/inmunología , Gastroenteritis/virología , Replicación Viral , Ratones Noqueados , Inmunidad Innata , Esparcimiento de VirusRESUMEN
The BloodChIP Xtra database (http://bloodchipXtra.vafaeelab.com/) facilitates genome-wide exploration and visualization of transcription factor (TF) occupancy and chromatin configuration in rare primary human hematopoietic stem (HSC-MPP) and progenitor (CMP, GMP, MEP) cells and acute myeloid leukemia (AML) cell lines (KG-1, ME-1, Kasumi1, TSU-1621-MT), along with chromatin accessibility and gene expression data from these and primary patient AMLs. BloodChIP Xtra features significantly more datasets than our earlier database BloodChIP (two primary cell types and two cell lines). Improved methodologies for determining TF occupancy and chromatin accessibility have led to increased availability of data for rare primary cell types across the spectrum of healthy and AML hematopoiesis. However, there is a continuing need for these data to be integrated in an easily accessible manner for gene-based queries and use in downstream applications. Here, we provide a user-friendly database based around genome-wide binding profiles of key hematopoietic TFs and histone marks in healthy stem/progenitor cell types. These are compared with binding profiles and chromatin accessibility derived from primary and cell line AML and integrated with expression data from corresponding cell types. All queries can be exported to construct TF-gene and protein-protein networks and evaluate the association of genes with specific cellular processes.
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Sitios de Unión , Perfilación de la Expresión Génica , Leucemia Mieloide Aguda , Humanos , Cromatina/genética , Regulación de la Expresión Génica , Leucemia Mieloide Aguda/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac, HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (heptad, PU.1, CTCF, STAG2) in HSPC subsets (stem/multipotent progenitors plus common myeloid, granulocyte macrophage, and megakaryocyte erythrocyte progenitors) and found TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs, including PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type-specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of TF complexes was at least partially regulated by features encoded in DNA sequence motifs. Taken together, this study comprehensively characterizes the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying data sets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analyzing aberrant regulatory networks in leukemic cells.
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Subunidad alfa 2 del Factor de Unión al Sitio Principal , Células Madre Hematopoyéticas , Humanos , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Células Madre Hematopoyéticas/metabolismo , Regulación de la Expresión Génica , Hematopoyesis/genética , Cromatina/metabolismoRESUMEN
Focusing laser light onto a very small target can produce the conditions for laboratory-scale nuclear fusion of hydrogen isotopes. The lack of accurate predictive models, which are essential for the design of high-performance laser-fusion experiments, is a major obstacle to achieving thermonuclear ignition. Here we report a statistical approach that was used to design and quantitatively predict the results of implosions of solid deuterium-tritium targets carried out with the 30-kilojoule OMEGA laser system, leading to tripling of the fusion yield to its highest value so far for direct-drive laser fusion. When scaled to the laser energies of the National Ignition Facility (1.9 megajoules), these targets are predicted to produce a fusion energy output of about 500 kilojoules-several times larger than the fusion yields currently achieved at that facility. This approach could guide the exploration of the vast parameter space of thermonuclear ignition conditions and enhance our understanding of laser-fusion physics.
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Interferons (IFNs) are among the first vertebrate immune pathways activated upon viral infection and are crucial for control of viral replication and dissemination, especially at mucosal surfaces as key locations for host exposure to pathogens. Inhibition of viral establishment and spread at and from these mucosal sites is paramount for preventing severe disease, while concomitantly limiting putative detrimental effects of inflammation. Here, we compare the roles of type I, II, and III IFNs in regulating three archetypal viruses - norovirus, herpes simplex virus, and severe acute respiratory virus coronavirus 2 (SARS-CoV-2) - which infect distinct mammalian mucosal tissues. Emerging paradigms include highly specific roles for IFNs in limiting local versus systemic infection, synergistic activities, and a spectrum of protective versus detrimental effects of IFNs during the infection response.
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COVID-19 , Virosis , Animales , Humanos , Inmunidad Innata , Interferones , Membrana Mucosa , SARS-CoV-2 , Replicación ViralRESUMEN
OBJECTIVES: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half-pack size item codes for IR formulations. DESIGN, SETTING: Population-based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS-eligible residents and IQVIA national opioid medicine sales data (PBS-subsidised and private prescriptions), 28 May 2018 - 6 June 2021. MAIN OUTCOME MEASURES: Mean amount of PBS-subsidised opioid medicines dispensed per day and mean overall amount sold per day - each expressed as oral morphine equivalent milligrams (OME) - overall, by formulation type (IR, CR), and by specific formulation. RESULTS: During the twelve months following the PBS changes, daily PBS-subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, -106 146 to -56 984 OME) than the mean daily level for 2018-20, a decline of 3.8% after adjusting for the pre-intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS-subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half-pack sizes comprised 8.4% of PBS-subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. CONCLUSIONS: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions.
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Trastornos Relacionados con Opioides , Tramadol , Humanos , Analgésicos Opioides/uso terapéutico , Análisis de Series de Tiempo Interrumpido , Trastornos Relacionados con Opioides/tratamiento farmacológico , Prescripciones de Medicamentos , Australia , Preparaciones de Acción Retardada/uso terapéutico , Pautas de la Práctica en MedicinaRESUMEN
Emerging single-cell technologies provide high-resolution measurements of distinct cellular modalities opening new avenues for generating detailed cellular atlases of many and diverse tissues. The high dimensionality, sparsity, and inaccuracy of single cell sequencing measurements, however, can obscure discriminatory information, mask cellular subtype variations and complicate downstream analyses which can limit our understanding of cell function and tissue heterogeneity. Here, we present a novel pre-processing method (scPSD) inspired by power spectral density analysis that enhances the accuracy for cell subtype separation from large-scale single-cell omics data. We comprehensively benchmarked our method on a wide range of single-cell RNA-sequencing datasets and showed that scPSD pre-processing, while being fast and scalable, significantly reduces data complexity, enhances cell-type separation, and enables rare cell identification. Additionally, we applied scPSD to transcriptomics and chromatin accessibility cell atlases and demonstrated its capacity to discriminate over 100 cell types across the whole organism and across different modalities of single-cell omics data.
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Análisis de la Célula Individual , Transcriptoma , Análisis de la Célula Individual/métodosRESUMEN
A typical single-cell RNA sequencing (scRNA-seq) experiment will measure on the order of 20 000 transcripts and thousands, if not millions, of cells. The high dimensionality of such data presents serious complications for traditional data analysis methods and, as such, methods to reduce dimensionality play an integral role in many analysis pipelines. However, few studies have benchmarked the performance of these methods on scRNA-seq data, with existing comparisons assessing performance via downstream analysis accuracy measures, which may confound the interpretation of their results. Here, we present the most comprehensive benchmark of dimensionality reduction methods in scRNA-seq data to date, utilizing over 300 000 compute hours to assess the performance of over 25 000 low-dimension embeddings across 33 dimensionality reduction methods and 55 scRNA-seq datasets. We employ a simple, yet novel, approach, which does not rely on the results of downstream analyses. Internal validation measures (IVMs), traditionally used as an unsupervised method to assess clustering performance, are repurposed to measure how well-formed biological clusters are after dimensionality reduction. Performance was further evaluated over nearly 200 000 000 iterations of DBSCAN, a density-based clustering algorithm, showing that hyperparameter optimization using IVMs as the objective function leads to near-optimal clustering. Methods were also assessed on the extent to which they preserve the global structure of the data, and on their computational memory and time requirements across a large range of sample sizes. Our comprehensive benchmarking analysis provides a valuable resource for researchers and aims to guide best practice for dimensionality reduction in scRNA-seq analyses, and we highlight Latent Dirichlet Allocation and Potential of Heat-diffusion for Affinity-based Transition Embedding as high-performing algorithms.
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Benchmarking , ARN Citoplasmático Pequeño/genética , Análisis de Secuencia de ARN/métodos , Algoritmos , Análisis por Conglomerados , Conjuntos de Datos como Asunto , Humanos , Reproducibilidad de los Resultados , Análisis de la Célula Individual/métodosRESUMEN
Interferons (IFNs) are key controllers of viral replication, with intact IFN responses suppressing virus growth and spread. Using the murine norovirus (MNoV) system, we show that IFNs exert selective pressure to limit the pathogenic evolutionary potential of this enteric virus. In animals lacking type I IFN signaling, the nonlethal MNoV strain CR6 rapidly acquired enhanced virulence via conversion of a single nucleotide. This nucleotide change resulted in amino acid substitution F514I in the viral capsid, which led to >10,000-fold higher replication in systemic organs including the brain. Pathogenicity was mediated by enhanced recruitment and infection of intestinal myeloid cells and increased extraintestinal dissemination of virus. Interestingly, the trade-off for this mutation was reduced fitness in an IFN-competent host, in which CR6 bearing F514I exhibited decreased intestinal replication and shedding. In an immunodeficient context, a spontaneous amino acid change can thus convert a relatively avirulent viral strain into a lethal pathogen.
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Infecciones por Caliciviridae/virología , Proteínas de la Cápside/genética , Norovirus/genética , Norovirus/patogenicidad , Virulencia/genética , Animales , Infecciones por Caliciviridae/genética , Infecciones por Caliciviridae/inmunología , Aptitud Genética/genética , Inmunidad Innata/inmunología , Ratones , Norovirus/inmunología , Polimorfismo de Nucleótido Simple , Virulencia/inmunología , Replicación ViralRESUMEN
In direct-drive inertial confinement fusion, the laser bandwidth reduces the laser imprinting seed of hydrodynamic instabilities. The impact of varying bandwidth on the performance of direct-drive DT-layered implosions was studied in targets with different hydrodynamic stability properties. The stability was controlled by changing the shell adiabat from (α_{F}≃5) (more stable) to (α_{F}≃3.5) (less stable). These experiments show that the performance of lower adiabat implosions improves considerably as the bandwidth is raised indicating that further bandwidth increases, beyond the current capabilities of OMEGA, would be greatly beneficial. These results suggest that the future generation of ultra-broadband lasers could enable achieving high convergence and possibly high gains in direct drive ICF.
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The aim of this study was to examine internal responsiveness and estimate minimally important differences (MIDs) for CLEFT-Q scales.In this prospective cohort study, participants completed the CLEFT-Q appearance and health-related quality of life (HRQL) scales before and six months after cleft-related surgery.Seven cleft centres in Canada, USA and UK participated.Patients were ages 8-29 years with CL/P.Patients underwent rhinoplasty, orthognathic or cleft lip scar revision surgery.Internal responsiveness was examined using Cohen's d effect sizes (ESs) based on the following interpretation: 0.20-0.49 small, 0.50-0.79 moderate and ≥ 0.80 large. MIDs were estimated using two distribution-based approaches.Participants had a rhinoplasty (n = 31), orthognathic (n = 21) or cleft lip scar revision (n = 18) surgery. Most participants were males (56%) and aged 8-11 years (41%). Following rhinoplasty, ESs were larger for the nose (0.92, p = 0.001) and nostrils (0.94, p < 0.001) scales than for the face scale (0.51, p = 0.003). MIDs ranged between 6.2-10.4. For orthognathic surgery, larger ES was observed for the jaws scale (1.80, p < 0.001) compared with the teeth (1.16, p < 0.001), face (1.15, p = 0.001) and lips (0.94, p < 0.001) scales. MIDs ranged between 5.9-14.4. In the cleft lip scar revision sample, the largest ES was observed for the nose scale (0.76, p = 0.03), followed by lips (0.58, p = 0.009) and cleft lip scar (0.50, p = 0.043) scales. MIDs ranged between 6.4-12.3.CLEFT-Q detected change in key outcomes for three cleft-specific surgeries, providing evidence of its responsiveness. Estimated MIDs will aid in interpreting this PROM.
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Labio Leporino , Masculino , Humanos , Femenino , Labio Leporino/cirugía , Estudios Prospectivos , Calidad de Vida , Cicatriz , LabioRESUMEN
Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains in vitro. We further demonstrate that CD300lf is essential for both oral and parenteral MNoV infection and to elicit anti-MNoV humoral responses in vivo. In mice deficient in STAT1 signaling, CD300lf is required for MNoV-induced lethality. Finally, we demonstrate that human CD300lf (huCD300lf) is not essential for HNoV infection, nor does huCD300lf inhibit binding of HNoV virus-like particles to glycans. Thus, we report huCD300lf is not a receptor for HNoV.
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Infecciones por Caliciviridae/virología , Especificidad del Huésped , Interacciones Huésped-Patógeno , Norovirus/metabolismo , Receptores Inmunológicos/metabolismo , Receptores Virales/metabolismo , Animales , Células HeLa , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Norovirus/crecimiento & desarrollo , Receptores Inmunológicos/fisiología , Tropismo ViralRESUMEN
Spherical implosions in inertial confinement fusion are inherently sensitive to perturbations that may arise from experimental constraints and errors. Control and mitigation of low-mode (long wavelength) perturbations is a key milestone to improving implosion performances. We present the first 3D radiation-hydrodynamic simulations of directly driven inertial confinement fusion implosions with an inline package for polarized crossed-beam energy transfer. Simulations match bang times, yields (separately accounting for laser-induced high modes and fuel age), hot spot flow velocities and direction, for which polarized crossed-beam energy transfer contributes to the systematic flow orientation evident in the OMEGA implosion database. Current levels of beam mispointing, imbalance, target offset, and asymmetry from polarized crossed-beam energy transfer degrade yields by more than 40%. The effectiveness of two mitigation strategies for low modes is explored.
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BACKGROUND: An emerging body of literature has indicated that broad, transdiagnostic dimensions of psychopathology are associated with alterations in brain structure across the life span. The current study aimed to investigate the relationship between brain structure and broad dimensions of psychopathology in the critical preadolescent period when psychopathology is emerging. METHODS: This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,875; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. RESULTS: Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, parental education, income, and maternal psychopathology. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There were no statistically significant relationships between psychopathology and cortical thickness in this sample of preadolescents. CONCLUSIONS: The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. Future research may focus on whether the widespread and pervasive relationships between general psychopathology and brain structure reflect cognitive dysfunction that is a feature across a range of mental illnesses.
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Trastornos Mentales , Psicopatología , Adolescente , Teorema de Bayes , Encéfalo , Niño , Cognición , Humanos , Masculino , Trastornos Mentales/psicologíaRESUMEN
Aims Traumatic brain injury (TBI) is a leading cause of preventable mortality and morbidity. Our aim was to examine the demographics, injury characteristics and management of TBI patients treated in an intensive care unit (ICU) in an Irish tertiary-level hospital with a neurosurgical department. Methods A retrospective, longitudinal study of all TBI patients treated in ICU between 2013-2018. Results 77% (n=171) were male and median age was 46 (Q1-Q3: 28-62). The most common mechanism of injury was fall from less than two meters (<2m) followed by road traffic accident (RTA). The proportion of injuries due to RTA increased over the six-year period (p=0.006). 41.4% (n=92) of injuries had reported alcohol involvement. Patients with fall<2m had double the median age and double the rate of alcohol involvement compared to those suffering RTA (p<0.001, p<0.001). The neurosurgical intervention rate was 74% (n=165). The median duration of ICU admission and of intracranial-pressure monitoring, advanced ventilation and inotropic therapy increased over the six-year period (p=0.031, p=0.038, p=0.033, p<0.001). Discussion This study's findings could inform precise and impactful public prevention measures. The increasing duration of ICU admission and of other interventions should be examined further for their effect on patient outcome and resource consumption.
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Lesiones Traumáticas del Encéfalo , Lesiones Traumáticas del Encéfalo/epidemiología , Lesiones Traumáticas del Encéfalo/terapia , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly.
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Envejecimiento/fisiología , Bases de Datos Factuales , Imagen de Difusión por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiología , Anciano , Anciano de 80 o más Años , Cognición/fisiología , Estudios de Cohortes , Estudios Transversales , Bases de Datos Factuales/tendencias , Imagen de Difusión por Resonancia Magnética/tendencias , Femenino , Humanos , Masculino , Reino Unido/epidemiologíaRESUMEN
CRISPR-Cas systems are a class of adaptive immune systems in prokaryotes that use small CRISPR RNAs (crRNAs) in conjunction with CRISPR-associated (Cas) nucleases to recognize and degrade foreign nucleic acids. Recent studies have revealed that Type III CRISPR-Cas systems synthesize second messenger molecules previously unknown to exist in prokaryotes, cyclic oligoadenylates (cOA). These molecules activate the Csm6 nuclease to promote RNA degradation and may also coordinate additional cellular responses to foreign nucleic acids. Although cOA production has been reconstituted and characterized for a few bacterial and archaeal Type III systems, cOA generation and its regulation have not been explored for the Staphylococcus epidermidis Type III-A CRISPR-Cas system, a longstanding model for CRISPR-Cas function. Here, we demonstrate that this system performs Mg2+-dependent synthesis of 3-6 nt cOA. We show that activation of cOA synthesis is perturbed by single nucleotide mismatches between the crRNA and target RNA at discrete positions, and that synthesis is antagonized by Csm3-mediated target RNA cleavage. Altogether, our results establish the requirements for cOA production in a model Type III CRISPR-Cas system and suggest a natural mechanism to dampen immunity once the foreign RNA is destroyed.
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Nucleótidos de Adenina/metabolismo , Proteínas Asociadas a CRISPR/metabolismo , Oligorribonucleótidos/metabolismo , ARN Bacteriano/metabolismo , Staphylococcus epidermidis/metabolismo , Nucleótidos de Adenina/biosíntesis , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Asociadas a CRISPR/química , Sistemas CRISPR-Cas , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Magnesio/metabolismo , Modelos Moleculares , Oligorribonucleótidos/biosíntesis , Polimorfismo de Nucleótido Simple , Sistemas de Mensajero SecundarioRESUMEN
Hot electrons generated by laser-plasma instabilities degrade the performance of laser-fusion implosions by preheating the DT fuel and reducing core compression. The hot-electron energy deposition in the DT fuel has been directly measured for the first time by comparing the hard x-ray signals between DT-layered and mass-equivalent ablator-only implosions. The electron energy deposition profile in the fuel is inferred through dedicated experiments using Cu-doped payloads of varying thickness. The measured preheat energy accurately explains the areal-density degradation observed in many OMEGA implosions. This technique can be used to assess the viability of the direct-drive approach to laser fusion with respect to the scaling of hot-electron preheat with laser energy.
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Statistical modeling of experimental and simulation databases has enabled the development of an accurate predictive capability for deuterium-tritium layered cryogenic implosions at the OMEGA laser [V. Gopalaswamy et al.,Nature 565, 581 (2019)10.1038/s41586-019-0877-0]. In this letter, a physics-based statistical mapping framework is described and used to uncover the dependencies of the fusion yield. This model is used to identify and quantify the degradation mechanisms of the fusion yield in direct-drive implosions on OMEGA. The yield is found to be reduced by the ratio of laser beam to target radius, the asymmetry in inferred ion temperatures from the â=1 mode, the time span over which tritium fuel has decayed, and parameters related to the implosion hydrodynamic stability. When adjusted for tritium decay and â=1 mode, the highest yield in OMEGA cryogenic implosions is predicted to exceed 2×10^{14} fusion reactions.
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Energy flow and balance in convergent systems beyond petapascal energy densities controls the fate of late-stage stars and the potential for controlling thermonuclear inertial fusion ignition. Time-resolved x-ray self-emission imaging combined with a Bayesian inference analysis is used to describe the energy flow and the potential information stored in the rebounding spherical shock at 0.22 PPa (2.2 Gbar or billions of atmospheres pressure). This analysis, together with a simple mechanical model, describes the trajectory of the shell and the time history of the pressure at the fuel-shell interface, ablation pressure, and energy partitioning including kinetic energy of the shell and internal energy of the fuel. The techniques used here provide a fully self-consistent uncertainty analysis of integrated implosion data, a thermodynamic-path independent measurement of pressure in the petapascal range, and can be used to deduce the energy flow in a wide variety of implosion systems to petapascal energy densities.