Functional and Biochemical Characterization of Dib1\u27s Role in Pre-Messenger RNA Splicing

The spliceosome is a dynamic macromolecular machine that undergoes a series of conformational rearrangements as it transitions between the several states required for accurate splicing. The transition from the B to Bact is a key part of spliceosome assembly and is defined by the departure of several proteins, including essential U5 component Dib1. Recent structural studies suggest that Dib1 has a role in preventing premature spliceosome activation, as it is positioned adjacent to the U6 snRNA ACAGAGA and the U5 loop I, but its mechanism is unknown. Our data indicate that Dib1 is a robust protein that tolerates incorporation of many mutations, even at positions thought to be key for its folding stability. However, we have identified two temperature-sensitive mutants that stall in vitro splicing prior to the first catalytic step and block assembly at the B complex. In addition, Dib1 readily exchanges in splicing extracts despite being a central component of the U5 snRNP, suggesting that the binding site of Dib1 is flexible. Structural analyses show that the overall conformation of Dib1 and the mutants are not affected by temperature, so the temperature sensitive defects most likely result from altered interactions between Dib1 and other spliceosomal components. Together, these data lead to a new understanding of Dib1\u27s role in the B to Bact transition and provide a model for how dynamic protein–RNA interactions contribute to the correct assembly of a complex molecular machine

Density, species, and size distribution of groupers (Serranidae) in three habitats at Elbow Reef, Florida Keys

We examined the density, size and species distribution of groupers in three habitats on an inshore-to-offshore transect across Elbow Reef, Florida Keys: high-relief spur-and-groove (4–9 m depth), relict spur-and-groove (10–20 m), and deep fore reef slope (21–30 m). Physical relief was greatest in the high-relief spur-and-groove (up to 3 m), lowest in the relict spur-and-groove habitat (30%). There were significant differences in the density, size, and species distribution of groupers among the three habitats. Graysby, Epinephelus cruentatus, was numerically dominant, constituting 82–91% of individual observed. Black grouper, Mycteroperca bonaci, and Nassau grouper, E. striatus, were more abundant in high to moderate relief habitats, whereas red hind, E. guttatus, was more abundant in the low-relief habitat. The size distribution was shifted towards smaller sizes in lowest relief habitat and towards larger sizes in areas with greater (\u3e0.5 m) vertical relief. We suggest that fishing pressure in the Florida Keys has resulted in an offshore grouper assemblage dominated by graysby, a small grouper species (length) which is not targeted by fishermen, and that habitat selection and biological interactions have significantly influenced the ecological structure of the grouper assemblage of this coral reef

Enhancing soil organic matter as a route to the ecological intensification of European arable systems

Soil organic matter (SOM) is declining in most agricultural ecosystems, impacting on multiple ecosystem services including erosion and flood prevention, climate and greenhouse gas regulation as well as other services which underpin crop production, such as nutrient cycling and pest control. Ecological intensification aims to enhance crop productivity, by including regulating and supporting ecosystem services management into agricultural practices. We investigate the potential for increased SOM to support the ecological intensification of arable systems by reducing the need for nitrogen fertiliser application and pest control. Using a large-scale European field trial implemented across 84 fields in 5 countries we tested whether increased SOM (using soil organic carbon as a proxy) helps recover yield in the absence of conventional nitrogen fertiliser and whether this also supports crops less favourable to key aphid pests. Greater SOM increased yield by 10%, but did not offset nitrogen fertiliser application entirely, which improved yield by 30%. Crop pest responses depended on species: Metopolophium dirhodum were more abundant in fertilised plots with high crop biomass, and although population growth rates of Sitobion avenae were enhanced by nitrogen fertiliser application in a cage trial, field populations were not affected. We conclude that under increased SOM and reduced fertilizer application, pest pressure can be reduced, while partially compensating for yield deficits linked to fertiliser reduction. If the benefits of reduced fertiliser application and increased SOM are considered in a wider environmental context, then a yield cost may become acceptable. Maintaining or increasing SOM is critical for achieving ecological intensification of European cereal production

Associations of Parent–Child Anxious and Depressive Symptoms When a Caregiver Has a History of Depression

We examined the associations between parent and child anxious and depressive symptoms controlling for co-occurring symptoms in both. One hundred and four families participated, including 131 9–15 year old children considered at risk for anxiety and/or depression due to a history of depression in a parent. Parents and children completed questionnaires assessing depressive and anxious symptoms. Linear Mixed Models analyses controlling for the alternate parent and child symptoms indicated that both parent and child depressive symptoms and parent and child anxious symptoms were positively associated. Parental depressive symptoms were not positively associated with child anxious symptoms, and parental anxious symptoms were not positively associated with child depressive symptoms. The findings provide evidence for positive specific links between parent and child development of same-syndrome, but not cross-syndrome, symptoms when a caregiver has a history of depression

The Complexity of Transferring Remote Monitoring and Virtual Care Technology Between Countries: Lessons From an International Workshop

International deployment of remote monitoring and virtual care (RMVC) technologies would efficiently harness their positive impact on outcomes. Since Canada and the United Kingdom have similar populations, health care systems, and digital health landscapes, transferring digital health innovations between them should be relatively straightforward. Yet examples of successful attempts are scarce. In a workshop, we identified 6 differences that may complicate RMVC transfer between Canada and the United Kingdom and provided recommendations for addressing them. These key differences include (1) minority groups, (2) physical geography, (3) clinical pathways, (4) value propositions, (5) governmental priorities and support for digital innovation, and (6) regulatory pathways. We detail 4 broad recommendations to plan for sustainability, including the need to formally consider how highlighted country-specific recommendations may impact RMVC and contingency planning to overcome challenges; the need to map which pathways are available as an innovator to support cross-country transfer; the need to report on and apply learnings from regulatory barriers and facilitators so that everyone may benefit; and the need to explore existing guidance to successfully transfer digital health solutions while developing further guidance (eg, extending the nonadoption, abandonment, scale-up, spread, sustainability framework for cross-country transfer). Finally, we present an ecosystem readiness checklist. Considering these recommendations will contribute to successful international deployment and an increased positive impact of RMVC technologies. Future directions should consider characterizing additional complexities associated with global transfer

Quantifying osmotic membrane fouling to enable comparisons across diverse processes

In this study, a method of in situ membrane fouling quantification is developed that enables comparisons of foulant accumulation between desalination processes with different membranes, driving forces, and feed solutions. Unlike the conventional metric of flux decline, which measures the response of a process to fouling, the proposed method quantifies the foulant accumulation. Foulant accumulation is parameterized by two variables, cake structural parameter and hydraulic diameter, that are calculated from flux measurements using a model for salt and water transport through fouled reverse osmosis (RO) and forward osmosis (FO) membranes, including dispersive mass transfer in the FO membrane support layer. Model results show that pressure declines through the foulant layer and can, in FO, reach negative absolute values at the membrane. Experimental alginate gel fouling rates are measured within a range of feed ionic compositions where cake hydraulic resistance is negligible. Using both flux decline and cake structural parameter as metrics, the effect of feed salinity on RO fouling is tested and RO is compared to FO. When RO is fouled with alginate, feed salinity and membrane permeability affect flux decline but not foulant accumulation rate. Between FO and RO, the initial rates of foulant accumulation are similar; however, FO exhibits slower flux decline, which causes greater foulant accumulation over time. The new methodology enables meaningful quantification and comparison of fouling rates with the aim of improving fundamental understanding of fouling processes.Center for Clean Water and Clean Energy at MIT and KFUPM (Project R4-CW-11)MIT Martin Family Society of Fellows for SustainabilityNational Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374

Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies

Background: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis. Methods: Independent searches will be conducted in multiple electronic databases to identify clinical and animal experimental studies comparing TAAR1 agonists with licensed antipsychotics or other control conditions in individuals with psychosis or animal models for psychosis, respectively. The primary outcomes will be overall psychotic symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. Two independent reviewers will conduct study selection, data extraction using predefined forms, and risk of bias assessment using suitable tools based on the study design. Ontologies will be developed to facilitate study identification and data extraction. Data from clinical and animal studies will be synthesized separately using random-effects meta-analysis if appropriate, or synthesis without meta-analysis. Study characteristics will be investigated as potential sources of heterogeneity. Confidence in the evidence for each outcome and source of evidence will be evaluated, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, an overall conclusion will be drawn in a triangulation meeting involving a multidisciplinary team of experts. We plan trimonthly updates of the review, and any modifications in the protocol will be documented. The review will be co-produced by multiple stakeholders aiming to produce impactful and relevant results and bridge the gap between preclinical and clinical research on psychosis

How can an understanding of plant-pollinator interactions contribute to global food security?

Pollination of crops by animals is an essential part of global food production, but evidence suggests that wild pollinator populations may be declining while a number of problems are besetting managed honey bee colonies. Animal-pollinated crops grown today, bred in an environment where pollination was less likely to limit fruit set, are often suboptimal in attracting and sustaining their pollinator populations. Research into plant-pollinator interactions is often conducted in a curiosity-driven, ecological framework, but may inform breeding and biotechnological approaches to enhance pollinator attraction and crop yield. In this article we review key topics in current plant-pollinator research that have potential roles in future crop breeding for enhanced global food security