A variety of criteria may influence the efficacy of networks of marine protected areas (MPA) designed to enhance biodiversity conservation and provide fisheries benefits. Meta‐analyses have evaluated ...the influence of MPA attributes on abundance, biomass, and size structure of harvested species, reporting that MPA size, age, depth, and connectivity influence the strength of MPA responses. However, few empirical MPA evaluation studies have used consistent sampling methodology across multiple MPAs and years. Our collaborative fisheries research program systematically sampled 12 no‐take or highly protective limited‐take MPAs and paired fished reference areas across a network spanning 1100 km of coastline to evaluate the factors driving MPA efficacy across a large geographic region. We found that increased size and age consistently contributed to increased fish catch, biomass, and positive species responses inside MPAs, while accounting for factors such as latitude, primary productivity, and distance to the nearest MPA. Our study provides a model framework to collaboratively engage diverse stakeholders in fisheries research and provide high‐quality data to assess the success of conservation strategies.
The glutamatergic system is increasingly being viewed as a promising target for the development of novel treatments for depression. The group III metabotropic glutamate (mGlu) receptors (mGlu4, 7 and ...8 receptors) in particular are beginning to show promise in this respect. It remains unclear how antidepressant medications modulate mGlu receptors. In this study we investigated the effects of three antidepressant treatments (fluoxetine, ketamine and electroconvulsive shock therapy (ECT)). Ketamine is an NMDA receptor antagonist which possess a rapid antidepressant therapeutic profile and moreover is effective in cases of treatment-resistant depression. Furthermore, ECT is also a therapeutic strategy possessing increased efficacy compared to conventional monoamine based therapies. The effect these two highly efficacious treatments have on hippocampal group III mGlu receptors remains completely unexplored. To redress this deficit we investigated the effects these treatments and the prototypical selective serotonin reuptake inhibitor (SSRI) fluoxetine would have on hippocampal group III mGlu receptor mRNA levels in naïve Sprague–Dawley rats and rats which had undergone early-life stress in the form of the maternal separation (MS) procedure. We found MS significantly reduced mGlu4 receptor expression and fluoxetine reversed this MS induced change. ECT and ketamine treatment significantly reduced mGlu4 receptor expression in non-separated (NS) animals while having no effect in MS animals. Fluoxetine and ECT significantly increased mGlu7 receptor expression in NS animals. This work demonstrates changes to mGlu4 receptor expression may be a lasting molecular change which occurs due to early-life stress. Taken together our data shows there are selective changes to group III mGlu receptors under basal and early-life stress conditions.
This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.
► Early-life stress-induced using maternal separation significantly reduced hippocampal mGlu4 receptor expression. ► Chronic fluoxetine reversed this early-life stress-induced change to mGlu4 expression. ► Chronic fluoxetine and ECT treatment significantly increased hippocampal mGlu7 receptor expression in NS animals.
Collaborative fisheries research programs engage stakeholders in data collection efforts, often with the benefit of increasing transparency about the status and management of natural resources. These ...programs are particularly important in marine systems, where management of recreational and commercial fisheries have historically been contentious. One such program is the California Collaborative Fisheries Research Program (CCFRP), which was designed in 2006 to engage recreational anglers in the scientific process and evaluate the efficacy of California’s network of marine protected areas. CCFRP began on the Central Coast of California and expanded statewide in 2017 to include six partner institutions in three regions: Northern, Central, and Southern California. To date, over 2,000 volunteer anglers have participated in the program, with many anglers volunteering for multiple years. However, the impacts of outreach, education, and collaborative research on those anglers at the statewide scale are currently unknown. Thus, the objective of the current study was to survey the statewide pool of volunteer anglers to assess the degree to which participation in CCFRP has influenced angler perceptions of MPAs, fisheries management, and conservation. We received 259 completed surveys out of a pool of 1,386 active anglers, equating to an 18.7% response rate. Participation in CCFRP resulted in a significant, positive impact on anglers’ attitudes towards MPAs in California across all regions. Anglers who participated in six or more CCFRP fishing trips had a more positive perception of MPAs than those who participated in fewer trips. Volunteer anglers across all regions perceived that they caught larger fishes, a higher abundance of fishes, and a greater diversity of species inside MPAs, consistent with the ecological findings of the program. These results highlight the benefits of involving community members in collaborative scientific research. Collaboration between researchers and the broader community increases transparency and trust between stakeholders, and results in greater understanding of natural resource dynamics, ultimately producing better management outcomes.
Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of ...compounds that may provide cardiometabolic benefits.
We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention. Associations between changes in salmon FSCs and changes in cardiometabolic health indicators (CHIs) were also explored.
For this secondary analysis of a randomized, crossover, controlled feeding trial, 41 participants consumed MED diets with 2 servings of salmon per week for 2 5-wk periods. CHIs were assessed, and fasting plasma was collected pre- and postintervention. Plasma, salmon, and 99 MED foods were analyzed using liquid chromatography-mass spectrometry-based metabolomics. Compounds were characterized as salmon FSCs if detected in all salmon replicates but none of the other foods. Metabolites of salmon FSCs were predicted using machine learning. For salmon FSCs and metabolites found in plasma, linear mixed-effect models were used to assess change from pre- to postintervention and associations with changes in CHIs.
Relative to the other 99 MED foods, there were 508 salmon FSCs with 237 unique metabolites. A total of 143 salmon FSCs and 106 metabolites were detected in plasma. Forty-eight salmon FSCs and 30 metabolites increased after the intervention (false discovery rate <0.05). Increases in 2 annotated salmon FSCs and 2 metabolites were associated with improvements in CHIs, including total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.
A data-driven nutrimetabolomics strategy identified salmon FSCs and their predicted metabolites that were detectable in plasma and changed after consumption of a salmon-containing MED diet. Findings support this approach for the discovery of compounds in foods that may serve, upon further validation, as biomarkers or act as bioactive components influential to health. The trials supporting this work were registered at NCT02573129 (Mediterranean-style diet intervention) and NCT05500976 (ongoing clinical trial).
The Orbiting Carbon Observatory-2 (OCO-2) is the first National Aeronautics and Space Administration (NASA) satellite designed to measure atmospheric carbon dioxide (CO2) with the accuracy, ...resolution, and coverage needed to quantify CO2 fluxes (sources and sinks) on regional scales. OCO-2 was successfully launched on 2 July 2014 and has gathered more than 2 years of observations. The v7/v7r operational data products from September 2014 to January 2016 are discussed here. On monthly timescales, 7 to 12 % of these measurements are sufficiently cloud and aerosol free to yield estimates of the column-averaged atmospheric CO2 dry air mole fraction, XCO2, that pass all quality tests. During the first year of operations, the observing strategy, instrument calibration, and retrieval algorithm were optimized to improve both the data yield and the accuracy of the products. With these changes, global maps of XCO2 derived from the OCO-2 data are revealing some of the most robust features of the atmospheric carbon cycle. This includes XCO2 enhancements co-located with intense fossil fuel emissions in eastern US and eastern China, which are most obvious between October and December, when the north–south XCO2 gradient is small. Enhanced XCO2 coincident with biomass burning in the Amazon, central Africa, and Indonesia is also evident in this season. In May and June, when the north–south XCO2 gradient is largest, these sources are less apparent in global maps. During this part of the year, OCO-2 maps show a more than 10 ppm reduction in XCO2 across the Northern Hemisphere, as photosynthesis by the land biosphere rapidly absorbs CO2. As the carbon cycle science community continues to analyze these OCO-2 data, information on regional-scale sources (emitters) and sinks (absorbers) which impart XCO2 changes on the order of 1 ppm, as well as far more subtle features, will emerge from this high-resolution global dataset.
Background Combining inhaled corticosteroids with long-acting β2 -agonists results in improved asthma symptom control and fewer asthma exacerbations compared with those seen after inhaled ...corticosteroids alone. However, there are limited data as to whether these beneficial effects are due to enhanced anti-inflammatory actions or whether such combination therapies affect airway remodeling in patients with asthma. Objective We sought to determine the effects of inhaled budesonide/formoterol combination therapy versus inhaled budesonide alone or inhaled placebo on allergen-induced airway responses, airway inflammation, and airway remodeling. Methods Fourteen asthmatic subjects with dual responses after allergen inhalation were included in this prospective, randomized, double-blind, 3-period crossover study. Outcomes included early and late asthmatic responses, changes in airway responsiveness, sputum eosinophilia measured before and after allergen challenge, numbers of airway submucosal myofibroblasts, and smooth muscle area measured before and after study treatment. Results Allergen-induced sputum eosinophilia was significantly reduced by combination treatment to a greater extent than by budesonide alone. Allergen inhalation resulted in a significant increase in submucosal tissue myofibroblast numbers and produced a significant decrease in percentage smooth muscle area. Combination therapy, but not budesonide monotherapy, significantly attenuated these changes in myofibroblast numbers and smooth muscle area. Conclusions The effects on allergen-induced changes in sputum eosinophils, airway myofibroblast numbers, and smooth muscle seen with combination therapy suggest that the benefits associated with this treatment might relate to effects on airway inflammation and remodeling. The attenuation of early asthmatic responses and airway hyperresponsiveness by combination treatment was likely due to the known functional antagonistic effect of formoterol.
Neoplastic cells self‐assemble in liquid‐overlay cultures into multicellular spheroids that resemble micrometastases and avascular regions of larger tumors. A Monte Carlo simulation based on ...Meakinapos;s cluster‐cluster aggregation model resolved the physical mechanisms by which LNCaP human prostate cancer cells aggregate in this environment. The best‐fit solution suggests that LNCaP cells aggregate with an adhesion probability of 0.5% when they migrate within a radius of influence between cell centers of 180 μm, 10 times the cell diameter. The sweeping radius of influence is indicative of cell tethering and/or chemotaxis and results in an intrinsic rate of self‐aggregation that increases from k11 = 1.5 h‐1 for single cells to k1010 = 17.5 h‐1 for 10‐mers. Similar rates are predicted by Smoluchowskiapos;s collision theory (1), suggesting that they are inherent properties of LNCaP liquid‐overlay culture. Aggregates form more compact structures in culture than during simulation as measured by the fractal dimension: DF = 1.74 ± 0.04 for 10‐mers in culture vs DF = 1.25 ± 0.10 for simulated 10‐mers. Additional restructuring would further extend the radius of influence and diminish adhesion. Applications of this work include the production of highly viable spheroids for drug testing and basic oncological research.
Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes, such iModulons ...represent specific cellular functions. The identification of iModulons enables accurate identification of genes necessary and sufficient for cross-species transfer of cellular functions. We demonstrate cross-species transfer of: 1) the biotransformation of vanillate to protocatechuate, 2) a malonate catabolic pathway, 3) a catabolic pathway for 2,3-butanediol, and 4) an antimicrobial resistance to ampicillin found in multiple Pseudomonas species to Escherichia coli. iModulon-based engineering is a transformative strategy as it includes all genes comprising the transferred cellular function, including genes without functional annotation. Adaptive laboratory evolution was deployed to optimize the cellular function transferred, revealing mutations in the host. Combining big data analytics and laboratory evolution thus enhances the level of understanding of systems biology, and synthetic biology for strain design and development.
Abstract
The bacterial respiratory electron transport system (ETS) is branched to allow condition-specific modulation of energy metabolism. There is a detailed understanding of the structural and ...biochemical features of respiratory enzymes; however, a holistic examination of the system and its plasticity is lacking. Here we generate four strains of
Escherichia coli
harboring unbranched ETS that pump 1, 2, 3, or 4 proton(s) per electron and characterized them using a combination of synergistic methods (adaptive laboratory evolution, multi-omic analyses, and computation of proteome allocation). We report that: (a) all four ETS variants evolve to a similar optimized growth rate, and (b) the laboratory evolutions generate specific rewiring of major energy-generating pathways, coupled to the ETS, to optimize ATP production capability. We thus define an Aero-Type System (ATS), which is a generalization of the aerobic bioenergetics and is a metabolic systems biology description of respiration and its inherent plasticity.
Efforts to identify the underlying structure of 40 survey items dealing with perceptions of medical errors are reported on the basis of responses from 195 medical residents. Factor analysis revealed ...that the medical errors perceptions were represented by a 10-factor solution. The external validity of these factors was examined relative to perceptions about the cost of medical errors, the cost of errors to health care, and the need for education and interventions to address errors. Results indicated that 13.9% of the variation in the perceived cost of medical errors and 17.1% of the variation in the perceived need for additional physician education was explained by the factor structure.