Changes In Abundance Research Articles

Removing high strength lincomycin in pharmaceutical wastewater by a bacteria microalgae consortium co-immobilized filter

Lincomycin (LIN) in pharmaceutical wastewater would enter municipal wastewater treatment plants and decrease their performance, leading to residual LIN enter the natural environment and pose serious eco-risk. In this study, a bacterium-microalgae consortium co-immobilized filter (BMCCF) was established and used to remove LIN in artificial pharmaceutical wastewater treatment plants effluents (PWWTPE). LIN removal mechanisms and degradation products’ eco-toxicity was studied, and the abundance change of class 1 integrase gene (intⅠ1) and antibiotic resistance genes (ARGs) was monitored. As a result, 98.54 % of 82 mg/L LIN was removed within 7 days, LIN removal was mainly attributed to bio-degradation by the Bacillus subtilis strain, and LIN degradation products were less toxic than their substrate. Therefore, the BMCCF established in this study provides a promising alternative for the bio-treatment of pharmaceutical wastewater containing high concentration of LIN.

Characterizing age-related changes in intact mitochondrial proteoforms in murine hearts using quantitative top-down proteomics

BackgroundCardiovascular diseases (CVDs) are the leading cause of death worldwide, and the prevalence of CVDs increases markedly with age. Due to the high energetic demand, the heart is highly sensitive to mitochondrial dysfunction. The complexity of the cardiac mitochondrial proteome hinders the development of effective strategies that target mitochondrial dysfunction in CVDs. Mammalian mitochondria are composed of over 1000 proteins, most of which can undergo post-translational modifications (PTMs). Top-down proteomics is a powerful technique for characterizing and quantifying proteoform sequence variations and PTMs. However, there are still knowledge gaps in the study of age-related mitochondrial proteoform changes using this technique. In this study, we used top-down proteomics to identify intact mitochondrial proteoforms in young and old hearts and determined changes in protein abundance and PTMs in cardiac aging.MethodsIntact mitochondria were isolated from the hearts of young (4-month-old) and old (24-25-month-old) mice. The mitochondria were lysed, and mitochondrial lysates were subjected to denaturation, reduction, and alkylation. For quantitative top-down analysis, there were 12 runs in total arising from 3 biological replicates in two conditions, with technical duplicates for each sample. The collected top-down datasets were deconvoluted and quantified, and then the proteoforms were identified.ResultsFrom a total of 12 LC-MS/MS runs, we identified 134 unique mitochondrial proteins in the different sub-mitochondrial compartments (OMM, IMS, IMM, matrix). 823 unique proteoforms in different mass ranges were identified. Compared to cardiac mitochondria of young mice, 7 proteoforms exhibited increased abundance and 13 proteoforms exhibited decreased abundance in cardiac mitochondria of old mice. Our analysis also detected PTMs of mitochondrial proteoforms, including N-terminal acetylation, lysine succinylation, lysine acetylation, oxidation, and phosphorylation. Data are available via ProteomeXchange with the identifier PXD051505.ConclusionBy combining mitochondrial protein enrichment using mitochondrial fractionation with quantitative top-down analysis using ultrahigh-pressure liquid chromatography (UPLC)-MS and label-free quantitation, we successfully identified and quantified intact proteoforms in the complex mitochondrial proteome. Using this approach, we detected age-related changes in abundance and PTMs of mitochondrial proteoforms in the heart.

The assembly and dynamics of ecological communities in an ever‐changing world

AbstractAlternative perspectives on the maintenance of biodiversity and the assembly of ecological communities suggest that both processes cannot be investigated simultaneously. In this concept and synthesis, we challenge this view by presenting major theoretical advances in structural stability and permanence theory. These advances, which provide complementary views, allow studying the short‐ and long‐term dynamics of ecological communities as changes in species richness, composition, and abundance. Here, the global attractor, technically named informational structure (IS), is the central element to construct from information of species' intrinsic growth rates and their strength and sign of interactions. The global attractor has four main properties: (1) It contains all the limits of what is feasible and unfeasible of the dynamical behavior of an ecological system, therefore, (2) it provides a thorough characterization of all combinations of species' richness and composition in which species can coexist (i.e., feasible and stable equilibrium), (3) as well as all connections (paths) of assembly between coexisting communities. Importantly, (4) such topology of coexisting communities and their connections changes when environmental (abiotic and biotic) variation affects the ability of species to grow and interact with others. Overall, these four properties allow switching from a traditional evaluation of species coexistence at equilibrium to a much more realistic nonequilibrium perspective where changes in the structure of the global attractor underlie the transient ecological dynamics. Several fields in ecology can benefit from the study of an IS. For instance, it can serve to evaluate community responses after the end of a perturbation, to design restoration trajectories, to study the consequences of biological invasions on the persistence of native species within communities, or to assess ecosystem health status. We illustrate this latter possibility with empirical observations of 7 years in Mediterranean annual grasslands. We document that extremely wet or dry years generate ISs supporting few coexisting communities and few assembly paths. The remaining communities distinguish winners from losers of ongoing climate change and indicate the limits to future community assembly opportunities. A fully tractable operational framework is readily available to understand and predict the assembly and dynamics of ecological communities in an ever‐changing world.

Tree species abundance changes at the edges of their climatic distribution: An interplay between climate change, plant traits and forest management

Abstract Climate change is anticipated to have an increased impact on tree populations located at the edges of their climatic tolerances. However, there is still uncertainty about how the interaction between climate change and functional traits drives changes in tree species abundance at climate edges, especially in the context of the abandonment of the traditional forest activity. We used data from ~445,000 monitored tree stems from 68 species in Spain to (1) quantify tree species abundance changes at the edges of their climatic distributions (cold and wet vs. warm and dry) over the last 25 years and (2) determine the impact of climate change, functional traits and forest densification (used here as an indicator of forest regrowth following anthropogenic disturbance) on these abundance changes. We developed a null model to test whether tree species abundance changes at the climate edges were higher or lower than expected, considering random stem gains and losses along the entire climate gradient. Across the study area, we found an average increase in tree species abundance over time. Our findings also show a higher than random average increase in tree species abundance at the cold and wet edge, but a random increase at the warm and dry edge. Tree species abundance changes along the entire climate gradient and in the edges were primarily associated with forest densification. However, the interaction between climate change and plant traits impacted tree species abundance changes at the climate edges. Tree species that invested more in their root systems and adopted more acquisitive leaf strategies showed greater increases in abundance in response to climate change. Synthesis: Our research emphasizes the crucial impact of historical forest management in shaping the current distribution of tree species. After controlling for the effect of forest management, climate change directly influenced tree demographics, favouring species based on their traits. As tree species regain their ecological niches after succession, climate change will determine their abundance by filtering for particular ecological strategies.

Vertical variation of antibiotic resistance genes and their interaction with environmental nutrients in sediments of Taihu lake

Antibiotic resistance is a growing environmental issue. As a sink for antibiotic resistance genes (ARGs), lake surface sediments are well known for the spread of ARGs. However, the distribution pattern of ARGs and their relationship with environmental factors in vertical sediment layers are unclear. In this study, we investigated the resistome distribution in sediment cores from Taihu Lake using metagenomic analysis. The results showed that the abundance of total ARGs increased by 153% as the sediment depth rose from 0 to 50 cm, and the ARG Shannon index significantly increased. Among all the ARG types, efflux pump genes (e.g., mexT and mexW) were dominant, especially in 40–50 cm sediment. The variation in ARG with depth described above was related to the changes in bacterial adaptation to environmental gradients. Specifically, sulfate and nitrate concentrations decreased with depth, and random forest analysis showed that they were the main factors affecting the changes in ARG abundance. Environmental factors were also found to indirectly impact the distribution of ARGs by affecting the bacterial community. Potential sulfate-reducing gene/nitrate-reducing gene-ARG co-hosts were annotated through metagenomic assembly. The dominant co-hosts, Curvibacter, and Comamonas, which were enriched in deeper sediments, may have contributed to the enrichment of ARGs in deep sediments. Overall, our findings demonstrated that bacterial-mediated sulfate and nitrate reduction was closely related to sediment resistance, which provided new insights into the control of antibiotic resistance.

A Bioconductor workflow for processing, evaluating, and interpreting expression proteomics data

Background Expression proteomics involves the global evaluation of protein abundances within a system. In turn, differential expression analysis can be used to investigate changes in protein abundance upon perturbation to such a system. Methods Here, we provide a workflow for the processing, analysis and interpretation of quantitative mass spectrometry-based expression proteomics data. This workflow utilises open-source R software packages from the Bioconductor project and guides users end-to-end and step-by-step through every stage of the analyses. As a use-case we generated expression proteomics data from HEK293 cells with and without a treatment. Of note, the experiment included cellular proteins labelled using tandem mass tag (TMT) technology and secreted proteins quantified using label-free quantitation (LFQ). Results The workflow explains the software infrastructure before focusing on data import, pre-processing and quality control. This is done individually for TMT and LFQ datasets. The application of statistical differential expression analysis is demonstrated, followed by interpretation via gene ontology enrichment analysis. Conclusions A comprehensive workflow for the processing, analysis and interpretation of expression proteomics is presented. The workflow is a valuable resource for the proteomics community and specifically beginners who are at least familiar with R who wish to understand and make data-driven decisions with regards to their analyses.

Striped Field Mouse Invading Human-Modified Environments of Lithuania during Last Five Decades

The striped field mouse (Apodemus agrarius) is expanding in several European countries, but the details of this process are not always documented due to a lack of long-term studies. We conducted an analysis of changes in relative abundances and proportions of A. agrarius in small mammal communities in nine different habitat groups in Lithuania during 1975–2023. We found an increase in the abundance and proportion of A. agrarius, increasing synanthropization of the species, and tolerance to anthropogenization of habitats. Temporal variations in the relative abundance and proportion of species were observed, with lower values in February–July and higher values in September–January. The main finding is a remarkable increase in species presence in the country after the 1990s, with a peak observed in the 2010s–2020s, confirmed by eight local studies. During these decades, it was the third most abundant species, representing 19.8–20.0% of the individuals caught. It is also important to note that A. agrarius has recently been most abundant in commensal habitats (0.029 ± 0.006 individuals/trap day), with the highest species proportion in agricultural areas (24.8 ± 1.8%). There are many indications that the expansion of A. agrarius in Lithuania is becoming invasive.

Source elimination of antibiotic resistance risk in aquaculture water by VUV/sulfite pretreatment

Antibiotic resistance risk in the aquaculture industry is increasing with the excessive consumption of antibiotics. Although various efficient technologies for the degradation of antibiotics are available, the potential risk from antibiotic resistance in treated waters is often overlooked. This study compared the risks of antibiotic resistance in anaerobic sludge fed with pretreated florfenicol (FLO) containing wastewater after four UV or vacuum UV (VUV)-driven ((V)UV-driven) pretreatments, and established the VUV/sulfite recirculating water system to validate the effect of controlling the antibiotic resistance risk in the actual aquaculture water. Metagenomics sequencing revealed that a remarkable decrease in the abundance of antibiotic resistance genes (ARGs) was observed in four different pretreated groups, and results among the four pretreated groups were sorted in descending order based on ARG abundance: UV > VUV > UV/sulfite > VUV/sulfite. The low abundance of ARGs from VUV/sulfite group was close to that in the CK group (wastewater without FLO and without any pretreatments), which was 0.41 copies/cell. From the perspective of the temporal changes in the relative abundance of floR, the abundance in VUV/sulfite group remained lower than 11.67 ± 0.73 during the cultivation time. Additionally, microbial diversity analysis found that Proteobacteria and Firmicutes were major carriers of ARGs. Two species from Burkholderiaceae and Rhodocyclales were identified as potential co-hosts to spread by the correlation analysis of the abundances between floR or intI1 and the top 50 genera. Finally, the abundances of ARGs and MGEs in the VUV/sulfite recirculating water system with actual aquaculture water were reduced by 39.15% and 46.04%, respectively, compared to that in the blank group without any pretreatment. This study verified that VUV/sulfite pretreatment system could effectively control the antibiotic resistance risk of ARGs proliferation and transfer in aquaculture water. Furthermore, the study demonstrated that the reduction of antibiotic antibacterial activity plays an important role in the source control of resistance risk.

Butterfly abundance changes in England are well associated with extreme climate events

Climate change exerts significant impacts on ecosystems through extreme climate events (ECEs), which are linked to various climate variables and can occur in different seasons. However, previous studies predominantly focus on a single type of ECE within specific seasons. We address this research gap by examining four typical types of ECEs: droughts, pluvials, heatwaves, and coldwaves, which are consistently defined and identified on a daily scale using a recently proposed statistical method. Butterflies in England serve as our study subject since their life stages occur throughout the year, and we had access to a 45-year dataset encompassing 57 butterfly species. First, we analyzed the correlation between abundance changes and the severity of ECEs, revealing varying sensitivity to ECEs across different life stages. Notably, abundance changes are negatively correlated with the severity of heatwaves in the hibernation, egg, and larval stages, as well as with the severity of pluvials in the larval, pupal, and adult stages. Second, we identified the most extreme climate events (MECEs) in England in the period from 1950 to 2020 and linked them with synchronized abundance changes for all species. MECEs in the sensitive stages of butterflies are frequently (for eight out of 11 MECEs) associated with synchronized decreases in their abundance. Our findings underscore the importance of considering diverse types of ECEs across all seasons to gain insights into their potential ecosystem effects. We draw attention to the fact that our analyses are primarily data-driven, with limited ecophysiological interpretation.

Evaluating the Effect of a Probiotic on Prevention of Diarrhea, Stress Response, and Social Interactions in a Colony of Macaca fascicularis

Background: Social housing changes are associated with diarrhea in macaques, presumably due to stress. Objective: Since probiotics are utilized in humans for diarrhea, we tested the effectiveness of a species- specific probiotic, SDPro™ (composition: ~2 billion CFU each of live Lactobacillus reuteri and Saccharomyces boulardii), to prevent relocation-associated diarrhea. Assessments of the gutmicrobiome and diarrhea severity were made. Behavioral observations and cortisol levels were examined after relocation to test the effects of the probiotic treatment. Methods: The probiotic was administered to 60 juvenile macaques of both sexes (Probiotic +) and outcomes were compared to 60 control (Probiotic -) macaques. The effects on gut microbiome composition were analyzed via 16s microbiome analysis in half the animals from both groups. Social behaviors were monitored twice-weekly in the morning and afternoon for five weeks following 10- days of SDPro™ administration in 56 subjects and hair cortisol was assayed. Results: Probiotic administration altered beta, but not alpha, diversity, and caused changes in taxa abundance at the phylum, genus, and species levels. The Probiotic + group was enriched in Firmicutes, Clostridium, and Lactobacillus and diminished in Bacteriodies (p’s < 0.05) compared to controls. Although SDPro™ did not alter diarrhea incidence following relocation, it reduced diarrhea severity in males only. Males also exhibited higher cortisol levels than females but there was no probiotic effect. Probiotic treatment had minor behavioral effects; the typical reduction in locomotion seen in the afternoon was eliminated. Conclusion: The results suggest that SDPro™ may be a viable tool to prevent relocation-induced diarrhea in juvenile male macaques.

Habitat type controls microarthropod community changes across a Magellanic sub-Antarctic elevation gradient

IntroductionElevation gradients are often used as a proxy for climate change as they allow comparisons of ecological responses over much larger temporal and spatial scales than is possible through experimental manipulations.MethodsHere, we tested how microarthropod communities (Collembola and Acari) are affected by climatic differences between sea level and 600 m a.s.l. on Navarino Island, in the Magellanic sub-Antarctic ecoregion of southern Chile (mean annual temperatures of 5.6 vs 3.1°C, respectively). We quantified microarthropod abundance, richness and community trait characteristics in dominant moss (Racomitrium lanuginosum and Polytrichum strictum) and lichen (Usnea trachycarpa, Pseudocyphellaria freycinetii and Stereocaulon alpinum) vegetation growing at both elevations. These moss and lichen genera are characterized by large morphological differences and allow testing of how habitat characteristics affect microarthropod community response across elevation gradients.ResultsCollembola and Acari community composition differed between the low and high elevation sites. Total abundance levels of Acari were maintained in each habitat across elevation, whereas Collembola richness strongly declined (50%) at high elevation in the moss habitats. Acari community differences across elevation were driven by relative abundance changes whereas the Collembola community lost species at higher elevation. An anticipated decline of smaller eudaphic Collembola at high elevation was only observed in the moss Racomitrium, reflecting potentially lower temperature buffering capacity and shelter options compared to Polytrichum. Lichens mostly supported larger epigeic species irrespective of elevation. There were no consistent patterns linking microarthropod communities with habitat water holding capacity or water loss rates across the studied habitats and elevation.DiscussionHabitat type and the genus of moss or lichen were associated with microarthropod community changes across elevation, including examples of declines, increases and no change. These findings highlight that community responses across gradients may not always relate to the generally hypothesized environmental variables (e.g. temperature variability) and that habitat characteristics should be taken into account when using elevation as a proxy for climate change.

Modulation of fecal microbiota and reductions in fecal antibiotic resistance genes (ARGs) driven by Weissella-fermented feed in growing pigs

Probiotics-induced feed fermentation can improve the composition of microbiota, leading to benefits in pig production. However, the influence of probiotics-driven feed fermentation on pollution reduction is limited. This study aimed to analyze the impact of Weissella-based feed fermentation on the chemical characteristics, changes in microbial abundance, and antibiotic resistance genes (ARGs). Moreover, the possible mechanism and the association among them was also analyzed. First, pigs reared on fermented feed exhibited improved growth performance. The fermentation group showed a significant reduction in emissions of total phosphorus (TP), total carbon (TC), organic matter (OM), copper (Cu), and zinc (Zn) levels in feces compared to the control group. The fermentation group also showed a significant decrease in the ARGs, especially for the tetX, tetW, tetQ, tetL, tetO, tet32, tet44, ermG, ermF, CfxA2, CfxA3, aph3-III, aadA, and ant9-I, compared to the control group. The primary functional microbiota, characterized by increased levels of Bifidobacterium, Megasphaera, and Mitsuokella, and decreased levels of Methanosphaera, and Ruminiclostridium, displayed both negative and positive correlations with ARGs, TC, TP, OM, Cu, and Zn. Furthermore, a significant association was observed between the alterations in microbiota and ARGs and the lactic acid concentration in the fermented feed. The molecular docking results showed a good fit between lactate dehydrogenase and three antibiotics, particularly tetracycline. In conclusion, these results offer novel targets and strategies to address environmental pollutants associated with pig farming.

Biotoxicity of silver nanoparticles complicated by the co-existence of micro-/nano-plastics

Silver nanoparticles (AgNP) and polystyrene (PS) plastics have been broadly utilized in various field, e.g., food storage, packaging materials, and medical therapies. However, investigation on the potential biotoxicity induced by the co-exposure to AgNP and PS plastics remains understudied. Thus, we performed this study to examine the toxicological profile of the co-exposure to AgNP and PS in mice. Biochemical and microbial characterizations were performed in mice receiving 90-day oral gavage feeding to examine the hepatotoxicity, neurotoxicity, inflammatory responses, gut microbial alterations. It has been found that the presence of plastic particles aggravates the toxicity of silver nanoparticle materials. Regardless of the plastic type and size, energy and choline metabolisms will be altered by the co-exposures. Moreover, microplastics may induce cell damage by modulating fatty acid peroxidation in unison with stimulating inflammatory responses. Due to the smaller size of nanoplastics, they may pass through blood-brain barrier to induce neuronal damage and increase vascular risks. Changes in the microbial functional abundances are sensitive to the microplastics doses. These results support the necessity of reducing the co-exposure between AgNP and multiscale plastics, and advocate further developments of biodegradable package materials to improve food safety.

Ferroptosis Integrates Mitochondrial Derangements and Pathological Inflammation to Promote Pulmonary Hypertension.

Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species (ROS) generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells (PAEC) exhibit cellular phenotypes that promote ferroptosis. Moreover, there is ectopic complement deposition and inflammatory macrophage accumulation in the pulmonary vasculature. However, the effects of ferroptosis inhibition on these pathogenic mechanisms and the cellular landscape of the pulmonary vasculature are incompletely defined. Multi-omics and physiological analyses evaluated how ferroptosis inhibition modulated preclinical PAH. The impact of AAV1-mediated expression of the pro-ferroptotic protein ACSL4 on PAH was determined, and a genetic association study in humans further probed the relationship between ferroptosis and pulmonary hypertension (PH). Ferrostatin-1, a small-molecule ferroptosis inhibitor, mitigated PAH severity in monocrotaline rats. RNA-seq and proteomics analyses demonstrated ferroptosis was associated with PAH severity. RNA-seq, proteomics, and confocal microscopy revealed complement activation and pro-inflammatory cytokines/chemokines were suppressed by ferrostatin-1. Additionally, ferrostatin-1 combatted changes in endothelial, smooth muscle, and interstitial macrophage abundance and gene activation patterns as revealed by deconvolution RNA-seq. Ferroptotic PAEC damage associated molecular patterns restructured the transcriptomic signature, mitochondrial morphology, and promoted proliferation of pulmonary artery smooth muscle cells, and created a pro-inflammatory phenotype in monocytes in vitro. AAV1-Acsl4 induced an inflammatory PAH phenotype in rats. Finally, single-nucleotide polymorphisms in six ferroptosis genes identified a potential link between ferroptosis and PH severity in the Vanderbilt BioVU repository. Ferroptosis promotes PAH through metabolic and inflammatory mechanisms in the pulmonary vasculature.

The Role of Propionate-Induced Rearrangement of Membrane Proteins in the Formation of the Virulent Phenotype of Crohn's Disease-Associated Adherent-Invasive Escherichia coli.

Adhesive-invasive E. coli has been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells and then, due to survival inside macrophages and dendritic cells, stimulate chronic inflammation. In previous reports, we have shown that passage of the CD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates and inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEC in two phenotypes-virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). Unlike ZvL2-GLU, ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. To activate neutrophils, bacterial opsonization is necessary. Differences in neutrophil NADH oxidase activation and ζ-potential for ZvL2-GLU and ZvL2-PA are associated with changes in membrane protein abundance, as demonstrated by differential 2D electrophoresis and LC-MS. The increase in ROS and cytokine production during the interaction of ZvL2-PA with neutrophils is associated with a rearrangement of the abundance of membrane proteins, which leads to the activation of Rcs and PhoP/Q signaling pathways and changes in the composition and/or modification of LPS. Certain isoforms of OmpA may play a role in the formation of the virulent phenotype of ZvL2-PA and participate in the activation of NADPH oxidase in neutrophils.

Notch1 Phase Separation Coupled Percolation facilitates target gene expression and enhancer looping

The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

Habitat preferences of Phycis blennoides (Pisces: Gadiformes): environmental factors and fishing-related ontogenic deepening

Phycis blennoides is a component of the ecosystem of the Atlantic waters of northern Spain and a species of commercial interest for fisheries in this region. However, little is known about the distribution of this species. The present study analyses the relationships between different environmental and spatial variables and distribution of P. blennoides. Biological (presence-absence, abundance, biomass and total length) and environmental data were collected from a bottom trawl survey carried out off the northern coast of Spain. These data were used in 2-step generalised additive models to examine both the relative significance of physical factors in influencing P. blennoides distribution and to generate density distribution maps. Additionally, the role of fishing effort on P. blennoides body size distribution with depth was analysed. Geospatial analyses showed that changes in annual abundance did not influence physical habitat preference. Most of the variation in spatial distribution was explained by the sampling position and depth. The analyses showed that P. blennoides exhibited habitat preferences in the waters of Galicia and the Cantabrian Sea, with higher values of presence, abundance and biomass on the upper slope and on fine-grained sediment bottoms. P. blennoides biomass increased with depth, probably due to the increased mean size of individuals with depth. Modelling results suggest that the observed ontogenetic deepening appears to be mainly driven by the life history strategy of the species, but is also reinforced by fishing effort.

Metabolomic characterization of human glioblastomas and patient plasma: a pilot study

Background Glioblastoma (GBM) is a clinically challenging primary brain tumor with poor survival outcome despite surgical resection and intensive chemoradiation. The metabolic heterogeneity of GBM can become biomarkers for treatment response, resistance, and outcome prediction. The aim of the study is to investigate metabolic distinctions between primary and recurrent GBM tissue and patient plasma to establish feasibility for metabolic profiling. Methods A single-center cohort study analyzed tissue and blood samples from 15 patients with GBM using untargeted metabolomic/lipidomic assays. Metabolomic, lipidomic, and biogenic amine analyses were conducted on GBM tissue and patient plasma at diagnosis and recurrence using untargeted mass spectrometry. The study utilized a small but longitudinally collected cohort to evaluate alteration in metabolites, lipids, and biogenic amines between specimens at diagnosis and recurrence. Results Exploratory analysis revealed significant alteration in metabolites, lipids, and biogenic amines between diagnostic and recurrent states in both tumor and plasma specimens. Notable metabolites differed at recurrence, including N-alpha-methylhistamine, glycerol-3-phosphate, phosphocholine, and succinic acid in tissue, and indole-3-acetate, and urea in plasma. Principal component analysis revealed distinct metabolomic profiles between tumor tissue and patient plasma. Distinct metabolic profiles were observed in GBM tissue and patient plasma at recurrence, demonstrating the feasibility of using metabolomic methodologies for longitudinal studies. One patient exhibited a unique tumor resistance signature at diagnosis, possibly indicating a high-risk metabolomic phenotype. Conclusions In this small cohort, the findings suggest the potential of metabolomic signatures of GBM tissue and patient plasma for risk stratification, outcome prediction, and the development of novel adjuvant metabolic-targeting therapies. The findings suggest metabolic discrepancies at diagnosis and recurrence in tissue and plasma, highlighting potential implications for evaluation of clinical response. The identification of significant changes in metabolite abundance emphasizes the need for larger studies using targeted metabolomics to validate and further explore these profiles.

Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids

A hexanucleotide repeat expansion (HRE) in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Human brain imaging and experimental studies indicate early changes in brain structure and connectivity in C9-ALS/FTD, even before symptom onset. Because these early disease phenotypes remain incompletely understood, we generated iPSC-derived cerebral organoid models from C9-ALS/FTD patients, presymptomatic C9ORF72-HRE (C9-HRE) carriers, and controls. Our work revealed the presence of all three C9-HRE-related molecular pathologies and developmental stage-dependent size phenotypes in cerebral organoids from C9-ALS/FTD patients. In addition, single-cell RNA sequencing identified changes in cell type abundance and distribution in C9-ALS/FTD organoids, including a reduction in the number of deep layer cortical neurons and the distribution of neural progenitors. Further, molecular and cellular analyses and patch-clamp electrophysiology detected various changes in synapse structure and function. Intriguingly, organoids from all presymptomatic C9-HRE carriers displayed C9-HRE molecular pathology, whereas the extent to which more downstream cellular defects, as found in C9-ALS/FTD models, were detected varied for the different presymptomatic C9-HRE cases. Together, these results unveil early changes in 3D human brain tissue organization and synaptic connectivity in C9-ALS/FTD that likely constitute initial pathologies crucial for understanding disease onset and the design of therapeutic strategies.

High-resolution functional mapping of RAD51C by saturation genome editing

Pathogenic variants in RAD51C confer an elevated risk of breast and ovarian cancer, while individuals homozygous for specific RAD51C alleles may develop Fanconi anemia. Using saturation genome editing (SGE), we functionally assess 9,188 unique variants, including >99.5% of all possible coding sequence single-nucleotide alterations. By computing changes in variant abundance and Gaussian mixture modeling (GMM), we functionally classify 3,094 variants to be disruptive and use clinical truth sets to reveal an accuracy/concordance of variant classification >99.9%. Cell fitness was the primary assay readout allowing us to observe a phenomenon where specific missense variants exhibit distinct depletion kinetics potentially suggesting that they represent hypomorphic alleles. We further explored our exhaustive functional map, revealing critical residues on the RAD51C structure and resolving variants found in cancer-segregating kindred. Furthermore, through interrogation of UK Biobank and a large multi-center ovarian cancer cohort, we find significant associations between SGE-depleted variants and cancer diagnoses.