Smyth, C. | Search bioRxiv

bioRxiv2026

Attenuation of climatic signals limits prediction of phytoplankton blooms in a temperate shelf sea

Phytoplankton blooms link climatic conditions to marine food webs and carbon cycling, yet relationships between climate forcing and bloom magnitude remain weak and inconsistent in shelf seas. Using a multi-decadal, high-frequency observational record from the western Irish Sea gyre, we investigated how climate variability influences nutrient dynamics and spring phytoplankton bloom development. Sea surface temperature, marine heatwave intensity and the North Atlantic Oscillation exhibited weak and inconsistent relationships with bloom intensity. However, climatic influences were more evident in nutrient dynamics, particularly the timing of seasonal nutrient drawdown, whereas the magnitude of nutrient utilisation was strongly constrained by winter nutrient inventories. Translation of nutrient drawdown into phytoplankton biomass showed marked attenuation: nitrate consumption explained little variability in bloom intensity, whereas silicate drawdown exhibited a moderate, non-deterministic association consistent with functional constraints on diatom growth and community structure. Our results reveal relationships between climate variability and ecosystem function weaken across successive ecosystem levels. While nutrient inventories provide strong constraints on nutrient use, additional ecological and stoichiometric processes influence how nutrient uptake is translated into phytoplankton biomass. Our findings suggest that weak climate-bloom relationships may arise from hierarchical ecological filtering and highlight the importance of biological constraints when assessing ecosystem responses to climate variability in shelf seas.

ecology↗

bioRxiv2025

A protective role of REM sleep in the pathological basal ganglia-cortical circuit of Parkinson's disease

Sleep disturbances have been shown to be intimately and bidirectionally related to disease progression across a wide range of neurodegenerative disorders including Parkinsons disease (PD) and Alzheimers disease. However, the precise neurophysiological mechanisms relating abnormal sleep to aberrant daytime network activity that accelerates disease progression has yet to be determined. We collected chronic, multi-night (n=40), intracranial cortico-basal recordings during sleep from a cohort of patients with PD along with paired polysomnography and morning self-reports. This revealed that longer duration (and shorter latency) of rapid eye movement (REM) sleep predicted reduced daytime resting beta (13-30 Hz) activity and cortico-basal functional and effective connectivity, features established to be pathophysiological in PD. Within REM sleep, stronger cortical delta activity specifically predicted reduced pathophysiological cortico-basal neural network features. Additionally, REM delta power significantly predicted greater self-reported morning alertness. These findings highlight a potentially protective role of REM sleep in cortico-basal network health in PD and daytime subjective experience, representing a potential target for closed loop neuromodulation therapies to impact neurodegenerative disease progression.

neuroscience↗

bioRxiv2024

Plasmids from a complex biome exist as communities

Plasmids play a crucial role in the spread of antimicrobial resistance genes (ARGs) across One Health due to their ability to transfer a wide range of ARGs within and across bacterial species and biomes. We sequenced 173 circularised plasmids transferred from wastewater treatment plant (WWTP) effluent into Escherichia coli and subsequently characterised their genetic content. Multiple multidrug resistant plasmids were identified with a significant number of mega plasmids (>100Kb). Plasmids existing in isolation were rare and almost all existed with other plasmids. Our results suggest that positive epistasis promotes plasmid persistence in WWTP populations in a similar manner to that identified in vitro via infectious transmission, varying properties against plasmid community backgrounds, interactions with a range of other plasmids, source-sink spill-over transmission within the plasmid community rather than the host bacteria and compensatory mutations. We have demonstrated that the plasmid paradox solutions apply to plasmid communities in addition to plasmid host interactions. Our study identified that rather than existing as lone entities plasmids co-exist in small packs, the protection is afforded to the pack not by all members but by one or two and many plasmids coast within this pack as they contain no obvious advantage to the host. Our findings show that we need to enter a new paradigm and study plasmids in packs rather than as single entities in order to understand their transmission across One Health.

microbiology↗

bioRxiv2023

Multi-night naturalistic cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings in Parkinson's disease

BackgroundSleep disturbance is a prevalent and highly disabling comorbidity in individuals with Parkinsons disease (PD) that leads to worsening of daytime symptoms, accelerated disease progression and reduced quality of life. ObjectivesWe aimed to investigate changes in sleep neurophysiology in PD particularly during non-rapid eye movement (NREM) sleep, both in the presence and absence of deep brain stimulation (DBS). MethodsMulti-night (n=58) intracranial recordings were performed at-home, from chronic electrocorticography and subcortical electrodes, with sensing-enabled DBS pulse generators, paired with portable polysomnography. Four people with PD and one person with cervical dystonia were evaluated to determine the neural structures, signals and connections modulated during NREM sleep and prior to spontaneous awakenings. Recordings were performed both ON and OFF DBS in the presence of conventional dopaminergic replacement medications. ResultsWe demonstrate an increase in cortico-basal slow wave activity in delta (1-4 Hz) and a decrease in beta (13-31 Hz) during NREM (N2 and N3) versus wakefulness in PD. Cortical-subcortical coherence was also found to be higher in the delta range and lower in the beta range during NREM versus wakefulness. DBS stimulation resulted in a further elevation in cortical delta and a decrease in alpha (8-13 Hz) and low beta (13-15 Hz) power compared to the OFF stimulation state. During NREM sleep, we observed a strong inverse interaction between subcortical beta and cortical slow wave activity and found that subcortical beta increases prior to spontaneous awakenings. ConclusionsChronic, multi-night recordings in PD reveal opposing sleep stage specific modulations of cortico-basal slow wave activity in delta and subcortical beta power and connectivity in NREM, effects that are enhanced in the presence of DBS. Within NREM specifically, subcortical beta and cortical delta are strongly inversely correlated and subcortical beta power is found to increase prior to and predict spontaneous awakenings. We find that DBS therapy appears to improve sleep in PD partially through direct modulation of cortico-basal beta and delta oscillations. Our findings help elucidate a contributory mechanism responsible for sleep disturbances in PD and highlight potential biomarkers for future precision neuromodulation therapies targeting sleep and spontaneous awakenings.

neuroscience↗

bioRxiv2020

Plasmids shape the diverse accessory resistomes of Escherichia coli ST131

The human gut microbiome includes beneficial, commensal and pathogenic bacteria that possess antimicrobial resistance (AMR) genes that exchange these predominantly through conjugative plasmids. Escherichia coli is a significant component of the gastrointestinal microbiome and is typically non-pathogenic in this niche. In contrast, extra-intestinal pathogenic E. coli (ExPEC) including ST131 may occupy other environments like the urinary tract or bloodstream where they express genes enabling AMR and host cell adhesion like type 1 fimbriae. The extent to which commensal E. coli and uropathogenic ExPEC ST131 share AMR genes remains understudied at a genomic level, and here we examined this using a preterm infant resistome. Here, individual ST131 had small differences in AMR gene content relative to a larger shared resistome. Comparisons with a range of plasmids common in ST131 showed that AMR gene composition was driven by conjugation, recombination and mobile genetic elements. Plasmid pEK499 had extended regions in most ST131 Clade C isolates, and it had evidence of a co-evolutionary signal based on protein-level interactions with chromosomal gene products, as did pEK204 that had a type IV fimbrial pil operon. ST131 possessed extensive diversity of selective type 1, type IV, P and F17-like fimbriae genes that was highest in subclade C2. The structure and composition of AMR genes, plasmids and fimbriae vary widely in ST131 Clade C and this may mediate pathogenicity and infection outcomes. Data SummaryThe following files are available on the FigShare project "Plasmids_ST131_resistome_2020" : O_LI The set of 794 AMR genes derived from [74] are available (with their protein sequence translation) at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961402. C_LIO_LI The AMR gene profiles per sample determined by their BLAST sequence similarity results against CARD are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961612. This dataset includes the PlasmidFinder results. It also includes other AMR database comparisons (ARG-ANNOT, ResFinder, MegaRes, VFDB and VirulenceFinder). C_LIO_LI The BLAST sequence similarity results for the fim, pil, pap and ucl operons genes versus 4,071 E. coli ST131 assemblies from Decano & Downing (2019) are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961711. C_LIO_LI The genome sequences and annotation files for reference genomes NCTC13441, EC958 and SE15, along with the assembled contigs for 83972 and 3_2_53FAA are available at FigShare at doi: dx.doi.org/10.6084/m9.figshare.11961813. C_LIO_LI The 4,071 E. coli ST131 genome assemblies from Decano & Downing (2019) are available at FigShare at doi: 10.6084/m9.figshare.11962278 (the first 1,680 assemblies) and at doi: dx.doi.org/10.6084/m9.figshare.11962557 (the second 2,391 assemblies). C_LI

genomics↗

bioRxiv2020

Scalable method for micro-CT analysis enables large scale quantitative characterization of brain lesions and implants

Anatomic evaluation is an important aspect of many studies in neuroscience; however, it often lacks information about the three-dimensional structure of the brain. Micro-CT imaging provides an excellent, nondestructive, method for the evaluation of brain structure, but current applications to neurophysiological or lesions studies require removal of the skull and hazardous chemicals, dehydration or embedding, limiting their scalability and utility. Here we present a protocol using eosin in combination with bone decalcification to enhance contrast in the tissue and then employ monochromatic and propagation phase-contrast micro-CT imaging to enable the imaging of brain structure with the preservation of the surrounding skull. Instead of relying on descriptive, time-consuming, or subjective methods, we develop simple quantitative analyses to map the locations of recording electrodes and to characterize the presence and extent of brain lesions.

neuroscience↗

bioRxiv2019

Antibiotic resistant and extended-spectrum β-lactamase producing faecal coliforms in wastewater treatment plant effluent

Wastewater treatment plants (WWTPs) provide optimal conditions for the maintenance and spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In this work we describe the occurrence of antibiotic resistant faecal coliforms and their mechanisms of antibiotic resistance in the effluent of two urban WWTPs in Ireland. Effluent samples were collected from two WWTPs in Spring and Autumn of 2015 and 2016. The bacterial susceptibility patterns to 13 antibiotics were determined. The phenotypic tests were carried out to identify AmpC or extended-spectrum {beta}-lactamase (ESBL) producers. The presence of ESBL genes were detected by PCR. Plasmids carrying ESBL genes were transformed into Escherichia coli DH5 recipient and underwent plasmid replicon typing to identify incompatibility groups. More than 90% of isolated faecal coliforms were resistant to amoxicillin and ampicillin, followed by tetracycline (up to 39.82%), ciprofloxacin (up to 31.42%) and trimethoprim (up to 37.61%). Faecal coliforms resistant to colistin and imipenem were detected in all effluent samples. Up to 53.98% of isolated faecal coliforms expressed a multi-drug resistance (MRD) phenotype. AmpC production was confirmed in 5.22% of isolates. The ESBL genes were confirmed for 11.84% of isolates (9.2% of isolates carried blaTEM, 1.4% blaSHV-12, 0.2% blaCTX-M-1 and 1% blaCTX-M-15). Plasmids extracted from 52 ESBL isolates were successfully transformed into recipient E. coli. The detected plasmid incompatibility groups included the IncF group, IncI1, IncHI1/2 and IncA/C. These results provide evidence that treated wastewater is polluted with ARB and MDR faecal coliforms and are sources of ESBL-producing, carbapenem and colistin resistant Enterobacteriaceae. ImportanceAntibiotic resistant bacteria (ARB) are an emerging environmental concern with a potential impact on human health. The results provide the evidence that treated wastewater is polluted with antibiotic resistant bacteria containing mobile resistance mechanisms of importance to clinical treatment of pathogens and multi-drug resistant (MDR) faecal coliforms. They are sources of relatively high proportions of ESBL-producing Enterobacteriaceae, and include carbapenem and colistin resistant Enterobacteriaceae. The significance of this study is the identification of the role of WWTPs as a potential control point to reduce or stop the movement of ESBL, MDR and colistin resistant bacteria into the environment from further upstream sources, such as human or animal waste.

microbiology↗

bioRxiv2019

Antibiotic resistant and extended-spectrum β-lactamase producing faecal coliforms in wastewater treatment plant effluent

Wastewater treatment plants (WWTPs) provide optimal conditions for the maintenance and spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In this work we describe the occurrence of antibiotic resistant faecal coliforms and their mechanisms of antibiotic resistance in the effluent of two urban WWTPs in Ireland. Effluent samples were collected from two WWTPs in Spring and Autumn of 2015 and 2016. The bacterial susceptibility patterns to 13 antibiotics were determined. The phenotypic tests were carried out to identify AmpC or extended-spectrum {beta}-lactamase (ESBL) producers. The presence of ESBL genes were detected by PCR. Plasmids carrying ESBL genes were transformed into Escherichia coli DH5 recipient and underwent plasmid replicon typing to identify incompatibility groups. More than 90% of isolated faecal coliforms were resistant to amoxicillin and ampicillin, followed by tetracycline (up to 39.82%), ciprofloxacin (up to 31.42%) and trimethoprim (up to 37.61%). Faecal coliforms resistant to colistin and imipenem were detected in all effluent samples. Up to 53.98% of isolated faecal coliforms expressed a multi-drug resistance (MRD) phenotype. AmpC production was confirmed in 5.22% of isolates. The ESBL genes were confirmed for 11.84% of isolates (9.2% of isolates carried blaTEM, 1.4% blaSHV-12, 0.2% blaCTX-M-1 and 1% blaCTX-M-15). Plasmids extracted from 52 ESBL isolates were successfully transformed into recipient E. coli. The detected plasmid incompatibility groups included the IncF group, IncI1, IncHI1/2 and IncA/C. These results provide evidence that treated wastewater is polluted with ARB and MDR faecal coliforms and are sources of ESBL-producing, carbapenem and colistin resistant Enterobacteriaceae. ImportanceAntibiotic resistant bacteria (ARB) are an emerging environmental concern with a potential impact on human health. The results provide the evidence that treated wastewater is polluted with antibiotic resistant bacteria containing mobile resistance mechanisms of importance to clinical treatment of pathogens and multi-drug resistant (MDR) faecal coliforms. They are sources of relatively high proportions of ESBL-producing Enterobacteriaceae, and include carbapenem and colistin resistant Enterobacteriaceae. The significance of this study is the identification of the role of WWTPs as a potential control point to reduce or stop the movement of ESBL, MDR and colistin resistant bacteria into the environment from further upstream sources, such as human or animal waste.

microbiology↗

bioRxiv2018

Knock-in rats expressing Cre and Flp recombinases at the Parvalbumin locus.

Rats have the ability to learn and perform sophisticated behavioral tasks, making them very useful for investigating neural circuit functions. In contrast to the extensive mouse genetic toolkit, the paucity of recombinase-expressing rat models has limited the ability to monitor and manipulate molecularly-defined neural populations in this species. Here we report the generation and validation of two knock-in rat strains expressing either Cre or Flp recombinase under the control of Parvalbumin (Pvalb), a gene expressed in the critical \"fast-spiking\" subset of inhibitory interneurons (FSIs). These strains were generated with CRISPR-Cas9 gene editing and show highly specific and penetrant labeling of Pvalb-expressing neurons, as demonstrated by in situ hybridization and immunohistochemistry. We validated these models in both prefrontal cortex and striatum using both ex vivo and in vivo approaches, including whole-cell recording, optogenetics, extracellular physiology and photometry. Our results demonstrate the utility of these new transgenic models for a wide range of neuroscience experiments.

neuroscience↗