Seeley et al., 2024 (Comment: A reexamination of Johnston et al., 2023, bed-scale impact and recovery of a commercially important intertidal seaweed. J. Exp. Mar. Biol. Ecol. 574) describe a number ...of reasons that they believe our study's experimental design was flawed and our inferential conclusions were incorrect. We believe that these claims are the result of misunderstandings of the objectives behind our sampling design and statistical analyses. Throughout this response to Seeley et al., we reiterate key objectives of our study design: examining rockweed harvest at a whole-bed scale, realistically capturing the effects of current commercial rockweed harvest methods in Maine, and using coastwide site averages to estimate effect sizes of rockweed harvest. The first claim by Seeley et al. that our study design severely undersampled rockweed beds ignores established sampling methodologies in rockweed research. The suggestion that our sampling design resulted in impact sites that were de facto control sites is not supported by our analyses that showed greater declines in mean rockweed height and biomass at impact sites relative to control sites. In response to their second claim that rockweed companies had control of key elements of our study design and execution, we detail our specific approaches to lessen any possibility for such conflicts to bias our findings. In the final section of our response, we present power analyses in support of our Before-After Control-Impact study design and we highlight the statistically significant effects of treatment on rockweed biomass that contradict Seeley et al.'s claim that we drew conclusions about biomass recovery based solely on large p-values.
As the value of ecosystem-based management (EBM) approaches is increasingly recognized in marine ecosystems, it is critical that the impacts of resource harvest are assessed at various spatial ...scales. This is particularly true for habitat-forming resources, such as wild seaweeds, that act as foundation species by physically structuring ecosystems. The impacts of spatially heterogeneous harvest may change with scale, and have different management implications based on the ecosystem process or organism under consideration. Ascophyllum nodosum (hereafter rockweed) is a canopy-forming fucoid seaweed endemic to rocky coastlines in the North Atlantic Ocean that has been harvested for centuries. We conducted a Before-After Control-Impact study of commercial rockweed harvest at 38 sites across the coast of Maine (USA) from 2018 to 2020 in an effort to understand impact and one-year recovery of two rockweed bed structural characteristics, height and biomass, at a scale similar to a single harvest event. Our results indicate that rockweed harvest is spatially heterogeneous at the scale of the rockweed bed, and as a result, the effect sizes of harvest at this scale are smaller than those reported in previous studies that assessed smaller spatial scales. Mean rockweed biomass recovered to pre-harvest values after one year of recovery, but mean rockweed height remained lower at impacted sites. While post-harvest recovery was generally high in our study, sites that experienced higher intensities of harvest were less likely to fully recover height or biomass one year post-harvest. Our findings provide resource managers with a bed-scale perspective that can inform EBM approaches, particularly for population-level management of harvested resources and impacts of harvest on highly mobile organisms—such as birds and fish—that interact with these ecosystems at larger spatial scales.
•Rockweed harvest is spatially heterogeneous at the scale of the rockweed bed.•Effects of harvest on mean rockweed height and biomass are smaller at large scales.•Biomass, but not height, recovers one year after harvest.•Ecosystem-based management can benefit from considering various spatial scales.
The importance of ecosystem-based management (EBM) frameworks for resource harvest has increased over the past several decades as ecosystems face numerous anthropogenic stressors. In these ...frameworks, resource managers must consider the suite of interactions that comprise food webs and how resource harvest drives responses in non-target organisms. In rocky intertidal zones along North Atlantic coastlines, rockweed (Ascophyllum nodosum)—a canopy-forming brown seaweed—has been commercially harvested for centuries, yet most research on the effects of harvest have focused on the responses of the target resource and the macroinvertebrate assemblage. In this study, we used a Before-After Control-Impact experiment to assess the bottom-up effects of commercial rockweed harvest on a high trophic-level consumer group (birds) in Maine (USA). Overall, there was no evidence for strong bottom-up forcing of rockweed harvest on birds' site visitation. There was a small (fewer than two birds) positive effect size of harvest during the one-year post-harvest recovery interval. Several of the trends observed for the full bird assemblage appear to be driven more strongly by the low tide than the high tide bird assemblage. Independent of treatment, site visitation by birds was low in our study (60% of surveys recorded no birds) and highlights questions about the use of rocky intertidal habitats relative to other habitat types in coastal birds' home ranges. To our knowledge, there are no comparable assemblage-level bird studies in this system that can provide context to our results. Further research on coastal birds’ habitat use within home ranges and food-web connections with rockweed-associated macroinvertebrates is needed to more confidently incorporate this high trophic-level consumer group into an EBM framework for a rocky intertidal resource harvest.
•Ecosystem-based management approaches are important in the rockweed (Ascophyllum nodosum) fishery, but knowledge gaps remain•There were both positive and negative effects of rockweed harvest on birds, but effect sizes were small•Low densities of birds during our surveys highlights the need to understand the relative contribution of rockweed habitats toward the total resource needs of coastal birds
The direct conversion of methane to methanol would have a wide reaching environmental and industrial impact. Copper-containing zeolites can perform this reaction at low temperatures and pressures at ...a previously defined O2-activated Cu2O2+ site. However, after autoreduction of the copper-containing zeolite mordenite and removal of the Cu2O2+ active site, the zeolite is still methane reactive. In this study, we use diffuse reflectance UV–vis spectroscopy, magnetic circular dichroism, resonance Raman spectroscopy, electron paramagnetic resonance, and X-ray absorption spectroscopy to unambiguously define a mononuclear CuOH+ as the CH4 reactive active site of the autoreduced zeolite. The rigorous identification of a mononuclear active site allows a reactivity comparison to the previously defined Cu2O2+ active site. We perform kinetic experiments to compare the reactivity of the CuOH+ and Cu2O2+ sites and find that the binuclear site is significantly more reactive. From the analysis of density functional theory calculations, we elucidate that this increased reactivity is a direct result of stabilization of the Cu2OH2+ H-atom abstraction product by electron delocalization over the two Cu cations via the bridging ligand. This significant increase in reactivity from electron delocalization over a binuclear active site provides new insights for the design of highly reactive oxidative catalysts.
Dysregulation of normal transcription factor activity is a common driver of disease. Therefore, the detection of aberrant transcription factor activity is important to understand disease ...pathogenesis. We have developed Priori, a method to predict transcription factor activity from RNA sequencing data. Priori has two key advantages over existing methods. First, Priori utilizes literature-supported regulatory information to identify transcription factor-target gene relationships. It then applies linear models to determine the impact of transcription factor regulation on the expression of its target genes. Second, results from a third-party benchmarking pipeline reveals that Priori detects aberrant activity from 124 single-gene perturbation experiments with higher sensitivity and specificity than 11 other methods. We applied Priori and other top-performing methods to predict transcription factor activity from two large primary patient datasets. Our work demonstrates that Priori uniquely discovered significant determinants of survival in breast cancer and identified mediators of drug response in leukemia.
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•Priori predicts transcription factor activity using prior regulatory information•Priori detects perturbed transcription factors better than 11 other methods•Priori uniquely identified FOXA1 activity as a determinant of survival in BIDC•Priori nominated FOXO1 activity as a mediator of venetoclax sensitivity in AML
Gene network; Molecular mechanism of gene regulation; Biocomputational method; Biological constraints
A marine Verrucosispora sp. isolated from the sponge Chondrilla caribensis f. caribensis was found to produce thiocoraline, a potent cytotoxic compound. Five new analogs of thiocoraline were isolated ...and represent the first analogs of thiocoraline. 22′-Deoxythiocoraline (2), thiochondrilline C (5), and 12′-sulfoxythiocoraline (6) demonstrated significant cytotoxicity against the A549 human cancer cell line with EC50 values of 0.13, 2.86, and 1.26 μM, respectively. The analogs provide insight into the SAR and biosynthesis of thiocoraline. The DP4 probability method was used to analyze ab initio NMR calculations to confirm stereochemical assignments.
Abstract
Background
Nephrotic syndrome (NS), a chronic kidney disease, is characterized by significant loss of protein in the urine causing hypoalbuminemia and edema. In general, ∼15% of ...childhood-onset cases do not respond to steroid therapy and are classified as steroid-resistant NS (SRNS). In ∼30% of cases with SRNS, a causative mutation can be detected in one of 44 monogenic SRNS genes. The gene LAMA5 encodes laminin-α5, an essential component of the glomerular basement membrane. Mice with a hypomorphic mutation in the orthologous gene Lama5 develop proteinuria and hematuria.
Methods
To identify additional monogenic causes of NS, we performed whole exome sequencing in 300 families with pediatric NS. In consanguineous families we applied homozygosity mapping to identify genomic candidate loci for the underlying recessive mutation.
Results
In three families, in whom mutations in known NS genes were excluded, but in whom a recessive, monogenic cause of NS was strongly suspected based on pedigree information, we identified homozygous variants of unknown significance (VUS) in the gene LAMA5. While all affected individuals had nonsyndromic NS with an early onset of disease, their clinical outcome and response to immunosuppressive therapy differed notably.
Conclusion
We here identify recessive VUS in the gene LAMA5 in patients with partially treatment-responsive NS. More data will be needed to determine the impact of these VUS in disease management. However, familial occurrence of disease, data from genetic mapping and a mouse model that recapitulates the NS phenotypes suggest that these genetic variants may be inherited factors that contribute to the development of NS in pediatric patients.
Premature birth affects more than 10% of live births, and is characterized by relative hyperoxia exposure in an immature host. Long-term consequences of preterm birth include decreased aerobic ...capacity, decreased muscular strength and endurance, and increased prevalence of metabolic diseases such as type 2 diabetes mellitus. Postnatal hyperoxia exposure in rodents is a well-established model of chronic lung disease of prematurity, and also recapitulates the pulmonary vascular, cardiovascular, and renal phenotype of premature birth. The objective of this study was to evaluate whether postnatal hyperoxia exposure in rats could recapitulate the skeletal and metabolic phenotype of premature birth, and to characterize the subcellular metabolic changes associated with postnatal hyperoxia exposure, with a secondary aim to evaluate sex differences in this model. Compared to control rats, male rats exposed to 14 days of postnatal hyperoxia then aged to 1 year demonstrated higher skeletal muscle fatigability, lower muscle mitochondrial oxidative capacity, more mitochondrial damage, and higher glycolytic enzyme expression. These differences were not present in female rats with the same postnatal hyperoxia exposure. This study demonstrates detrimental mitochondrial and muscular outcomes in the adult male rat exposed to postnatal hyperoxia. Given that young adults born premature also demonstrate skeletal muscle dysfunction, future studies are merited to determine whether this dysfunction as well as reduced aerobic capacity is due to reduced mitochondrial oxidative capacity and metabolic dysfunction.
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