Transcriptome analyses reveal SR45 to be a neutral splicing regulator and a suppressor of innate immunity in Arabidopsis thaliana

Regulation of pre-mRNA splicing diversifies protein products and affects many biological processes. Arabidopsis thaliana Serine/Arginine-rich 45 (SR45), regulates pre-mRNA splicing by interacting with other regulatory proteins and spliceosomal subunits. Although SR45 has orthologs in diverse eukaryotes, including human RNPS1, the sr45–1 null mutant is viable. Narrow flower petals and reduced seed formation suggest that SR45 regulates genes involved in diverse processes, including reproduction. To understand how SR45 is involved in the regulation of reproductive processes, we studied mRNA from the wild-type and sr45–1 inflorescences using RNA-seq, and identified SR45-bound RNAs by immunoprecipitation. Using a variety of bioinformatics tools, we identified a total of 358 SR45 differentially regulated (SDR) genes, 542 SR45-dependent alternative splicing (SAS) events, and 1812 SR45-associated RNAs (SARs). There is little overlap between SDR genes and SAS genes, and neither set of genes is enriched for flower or seed development. However, transcripts from reproductive process genes are significantly overrepresented in SARs. In exploring the fate of SARs, we found that a total of 81 SARs are subject to alternative splicing, while 14 of them are known Nonsense-Mediated Decay (NMD) targets. Motifs related to GGNGG are enriched both in SARs and near different types of SAS events, suggesting that SR45 recognizes this motif directly. Genes involved in plant defense are significantly over-represented among genes whose expression is suppressed by SR45, and sr45–1 plants do indeed show enhanced immunity. We find that SR45 is a suppressor of innate immunity. We find that a single motif (GGNGG) is highly enriched in both RNAs bound by SR45 and in sequences near SR45- dependent alternative splicing events in inflorescence tissue. We find that the alternative splicing events regulated by SR45 are enriched for this motif whether the effect of SR45 is activation or repression of the particular event. Thus, our data suggests that SR45 acts to control splice site choice in a way that defies simple categorization as an activator or repressor of splicing.https://doi.org/10.1186/s12864-017-4183-

Convergence of a second-order scheme for non-local conservation laws

In this article, we present the convergence analysis of a second-order numerical scheme for traffic flow models that incorporate non-local conservation laws. We combine a MUSCL-type spatial reconstruction with strong stability preserving Runge-Kutta time-stepping to devise a fully discrete second-order scheme. The resulting scheme is shown to converge to a weak solution by establishing the maximum principle, bounded variation estimates and L1 Lipschitz continuity in time. Further, using a space-step dependent slope limiter, we prove its convergence to the entropy solution. We also propose a MUSCL-Hancock type second-order scheme which requires only one intermediate stage unlike the Runge-Kutta schemes and is easier to implement. The performance of the proposed second-order schemes in comparison to a first-order scheme is demonstrated through several numerical experiments

Catalyst: Fast and flexible modeling of reaction networks.

We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs. Through comprehensive benchmarks, we demonstrate that Catalyst simulation runtimes are often one to two orders of magnitude faster than other popular tools. More broadly, Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying CRNs; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for numerical solvers. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in numerical solvers. Finally, we demonstrate Catalyst's broad extensibility and composability by highlighting how it can compose with a variety of Julia libraries, and how existing open-source biological modeling projects have extended its intermediate representation

Catalyst: Fast and flexible modeling of reaction networks

Acknowledgements: The authors thank the 26 other individuals who contributed commits to Catalyst, the Catalyst tutorials, and the Catalyst documentation, along with the many users who have offered suggestions and opened issues. The authors acknowledge the MIT SuperCloud and Lincoln Laboratory Supercomputing Center for providing (HPC, database, consultation) resources that have contributed to the research results reported within this paper/report.Funder: 2021 Google Summer of Code FellowshipWe introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs. Through comprehensive benchmarks, we demonstrate that Catalyst simulation runtimes are often one to two orders of magnitude faster than other popular tools. More broadly, Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying CRNs; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for numerical solvers. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in numerical solvers. Finally, we demonstrate Catalyst’s broad extensibility and composability by highlighting how it can compose with a variety of Julia libraries, and how existing open-source biological modeling projects have extended its intermediate representation.</jats:p

A Suite of Mobile Conversational Agents for Daily Stress Management (Popbots): Mixed Methods Exploratory Study

BackgroundApproximately 60%-80% of the primary care visits have a psychological stress component, but only 3% of patients receive stress management advice during these visits. Given recent advances in natural language processing, there is renewed interest in mental health chatbots. Conversational agents that can understand a user’s problems and deliver advice that mitigates the effects of daily stress could be an effective public health tool. However, such systems are complex to build and costly to develop. ObjectiveTo address these challenges, our aim is to develop and evaluate a fully automated mobile suite of shallow chatbots—we call them Popbots—that may serve as a new species of chatbots and further complement human assistance in an ecosystem of stress management support. MethodsAfter conducting an exploratory Wizard of Oz study (N=14) to evaluate the feasibility of a suite of multiple chatbots, we conducted a web-based study (N=47) to evaluate the implementation of our prototype. Each participant was randomly assigned to a different chatbot designed on the basis of a proven cognitive or behavioral intervention method. To measure the effectiveness of the chatbots, the participants’ stress levels were determined using self-reported psychometric evaluations (eg, web-based daily surveys and Patient Health Questionnaire-4). The participants in these studies were recruited through email and enrolled on the web, and some of them participated in follow-up interviews that were conducted in person or on the web (as necessary). ResultsOf the 47 participants, 31 (66%) completed the main study. The findings suggest that the users viewed the conversations with our chatbots as helpful or at least neutral and came away with increasingly positive sentiment toward the use of chatbots for proactive stress management. Moreover, those users who used the system more often (ie, they had more than or equal to the median number of conversations) noted a decrease in depression symptoms compared with those who used the system less often based on a Wilcoxon signed-rank test (W=91.50; Z=−2.54; P=.01; r=0.47). The follow-up interviews with a subset of the participants indicated that half of the common daily stressors could be discussed with chatbots, potentially reducing the burden on human coping resources. ConclusionsOur work suggests that suites of shallow chatbots may offer benefits for both users and designers. As a result, this study’s contributions include the design and evaluation of a novel suite of shallow chatbots for daily stress management, a summary of benefits and challenges associated with random delivery of multiple conversational interventions, and design guidelines and directions for future research into similar systems, including authoring chatbot systems and artificial intelligence–enabled recommendation algorithms