Activity

An amendment to this paper has been published and can be accessed via a link at the top of the paper.We report temporal patterns of viral shedding in 94 patients with laboratory-confirmed COVID-19 and modeled COVID-19 infectiousness profiles from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% (95% confidence interval, 25-69%) of secondary cases were infected during the index cases’ presymptomatic stage, in settings with substantial household clustering, active case finding and quarantine outside the home. Disease control measures should be adjusted to account for probable substantial presymptomatic transmission.An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.PURPOSE The increasing use of electronic health records (EHRs) and biobanks offers unique opportunities to study Mendelian diseases. learn more We described a novel approach to summarize clinical manifestations from patient EHRs into phenotypic evidence for cystic fibrosis (CF) with potential to alert unrecognized patients of the disease. METHODS We estimated genetically predicted expression (GReX) of cystic fibrosis transmembrane conductance regulator (CFTR) and tested for association with clinical diagnoses in the Vanderbilt University biobank (N = 9142 persons of European descent with 71 cases of CF). The top associated EHR phenotypes were assessed in combination as a phenotype risk score (PheRS) for discriminating CF case status in an additional 2.8 million patients from Vanderbilt University Medical Center (VUMC) and 125,305 adult patients including 25,314 CF cases from MarketScan, an independent external cohort. RESULTS GReX of CFTR was associated with EHR phenotypes consistent with CF. PheRS constructed using the EHR phenotypes and weights discovered by the genetic associations improved discriminative power for CF over the initially proposed PheRS in both VUMC and MarketScan. CONCLUSION Our study demonstrates the power of EHRs for clinical description of CF and the benefits of using a genetics-informed weighing scheme in construction of a phenotype risk score. This research may find broad applications for phenomic studies of Mendelian disease genes.The direct cleavage of otherwise inert C-H bonds has emerged as a sustainable approach for organic synthesis; in contrast to other approaches, these reactions result in the formation of fewer undesired by-products and do not require pre-functionalization steps. In recent years, oxidative C-H/N-H alkyne annulations and C-H oxygenations were realized by 3d metals. Unfortunately, most of these reactions require stoichiometric amounts of often toxic chemical oxidants. This protocol provides a general method for cobaltaelectro-catalyzed C-H activations of benzamides. Here, anodic oxidation obviates the need for a chemical oxidant and uses 10-20% of a more environmentally benign, inexpensive catalyst. We outline a detailed and precise description of the designed electrolytic cell for metallaelectrocatalysis, including readily available electrode materials and electrode holders. The custom-made device is further compared with the commercially available and standardized ElectraSyn 2.0 electrochemistry kit. As example applications of this approach, we describe cobaltaelectro-catalyzed C-H activation protocols for the direct C-H oxygenation of benzamides and resource-economical synthesis of isoquinolones. The cobaltaelectrocatalysis setup and reaction take about 17 h, while an additional 5 h have to be anticipated for workup and chromatographic purification. The methods described herein feature broad functional group tolerance, operational simplicity, low waste-product formation and an overall exceptional level of resource economy.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Predicting the consequences of manipulating genotype (G) and agronomic management (M) on agricultural ecosystem performances under future environmental (E) conditions remains a challenge. Crop modelling has the potential to enable society to assess the efficacy of G × M technologies to mitigate and adapt crop production systems to climate change. Despite recent achievements, dedicated research to develop and improve modelling capabilities from gene to global scales is needed to provide guidance on designing G × M adaptation strategies with full consideration of their impacts on both crop productivity and ecosystem sustainability under varying climatic conditions. Opportunities to advance the multiscale crop modelling framework include representing crop genetic traits, interfacing crop models with large-scale models, improving the representation of physiological responses to climate change and management practices, closing data gaps and harnessing multisource data to improve model predictability and enable identification of emergent relationships. A fundamental challenge in multiscale prediction is the balance between process details required to assess the intervention and predictability of the system at the scales feasible to measure the impact. An advanced multiscale crop modelling framework will enable a gene-to-farm design of resilient and sustainable crop production systems under a changing climate at regional-to-global scales.Decoding wound signalling in plants is critical for understanding various aspects of plant sciences, from pest resistance to secondary metabolite and phytohormone biosynthesis. The plant defence responses are known to primarily involve NADPH-oxidase-mediated H2O2 and Ca2+ signalling pathways, which propagate across long distances through the plant vasculature and tissues. Using non-destructive optical nanosensors, we find that the H2O2 concentration profile post-wounding follows a logistic waveform for six plant species lettuce (Lactuca sativa), arugula (Eruca sativa), spinach (Spinacia oleracea), strawberry blite (Blitum capitatum), sorrel (Rumex acetosa) and Arabidopsis thaliana, ranked in order of wave speed from 0.44 to 3.10 cm min-1. The H2O2 wave tracks the concomitant surface potential wave measured electrochemically. We show that the plant RbohD glutamate-receptor-like channels (GLR3.3 and GLR3.6) are all critical to the propagation of the wound-induced H2O2 wave. Our findings highlight the utility of a new type of nanosensor probe that is species-independent and capable of real-time, spatial and temporal biochemical measurements in plants.