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Brooks, E.

Publications and source records attributed to Brooks, E..

13 recordsLinked to original sources

Beta power modulation supports micro-consolidation of implicit motor sequences

The consolidation of novel motor skills has traditionally been investigated over the timescale of hours-days following practice. However, a growing body of evidence has demonstrated that consolidation of skills occurs more rapidly across a scale of seconds - a process termed micro-consolidation. Micro-consolidation of explicitly cued motor sequences is supported by frontoparietal beta oscillations. Whether beta power modulation is a common mechanism supporting rapid consolidation of other forms of skill learning, such as implicit sequence learning, is yet to be elucidated. 72 healthy adults aged 18-35 (55% female) completed a serial reaction time task with concurrent electroencephalography recording. In line with our previous work, we show that the early fast learning on an implicit sequence task is primarily expressed as micro-offline gains during brief rest periods between periods of practice. Beta power was modulated as a function of active practice vs rest epochs (i.e., event-related synchronisation/desynchronisation), and here we demonstrate that micro-offline gains are associated with this modulation of beta power during the rest epochs. This relationship was specific to the beta frequency, and was not observed across either mu or gamma bands. Overall, in line with seminal work implicating beta in early explicit motor learning, our results indicate that beta is a shared neurophysiological signature of micro-consolidation of implicit sequences. Key points summary- Recent evidence demonstrates rapid consolidation of motor skills over seconds, termed micro-consolidation. - Seminal work has implicated beta oscillations in early explicit motor learning, though whether beta supports rapid consolidation of other forms of skill learning is unclear. - Using electroencephalography, we demonstrate that beta modulation is a neurophysiological signature of micro-consolidation of implicitly learnt motor sequences. - Lower beta at rest is associated with a higher degree of micro-consolidation. - Our findings shed critical new insight into the neurophysiological mechanisms mediating rapid consolidation of implicit motor skills during early fast learning.

neuroscience↗

Observing concurrent subcellular dynamics in large living tissues

An outstanding question in eukaryotic biology is the mechanistic connection between events occurring at (sub)cellular levels (time scales of milliseconds to minutes) to those at the tissue levels (tens of minutes to months). Deciphering such mechanisms requires imaging approaches capable of simultaneously achieving high spatial and temporal resolutions for large samples over long periods of time. Here, we demonstrate Airy beam-based light sheet microscopy of organelles in tens to hundreds of cells in a few hundred micrometre-wide tissue environments. We achieve a typical resolution of 320 nm over 266 x 266 x 100 m3 volumes at a temporal rate of 0.05 Hz, typically with generally used fluorophores such as Green Fluorescent Protein, over extended periods of time that allow tracking of organelle and protein dynamics. We validated our approach across different length and time scales by imaging mitochondria and endosome dynamics in very large fields of view in zebrafish tissue, molecular assemblies of myosin as gastrulation proceeds in Drosophila embryos, 3D mitochondrial streaming in mouse oocytes, pressure-driven motility and protrusions in amoebae, mitochondrial dynamics in cancer spheroids, 5 -colour fast imaging in iBlastoids, and endosomal dynamics in single cells. Through these model systems, we demonstrate the versatility of Airy beam light sheet microscopy to image large tissues at unprecedented high resolution; to capture dynamics in photosensitive, delicate samples; and to screen 3D samples. We anticipate that our Airy beam-based approach will represent a pivotal advance in cellular biology--especially developmental biology--as it provides, for the first time, true subcellular resolution over large imaging volumes with high temporal resolution.

developmental biology↗

The mechanosensitive protein Zyxin influences Hippo signalling and tissue growth via adherens junctions and basal spot junctions in Drosophila

Physical forces like tension and compression have a central role in the growth and morphogenesis of tissues. Cell-cell junctions and the actin cytoskeleton are key mediators of physical forces and influence activity of signalling networks like the Hippo pathway. Here, we show that the mechanosensitive proteins Zyxin and Ajuba work in concert to limit Hippo signalling and promote Drosophila epithelial tissue growth. Zyxin recruits both Ajuba and the central Hippo pathway kinase Warts to adherens junctions and basal spot junctions, and limit Warts activity by segregating it from Hippo pathway activator proteins. Zyxin also promotes the transmission of actomyosin tension to adherens junctions in growing epithelial tissues, indicating conservation of this function. Thus, we provide new insights into how Zyxin couples mechanical cues and Hippo pathway-dependent tissue growth and highlight the importance of basal spot junctions and their associated actomyosin network in epithelial tissue development.

developmental biology↗

High-intensity cardiovascular exercise facilitates online motor skill learning, with no effect of BDNF genotype

Previous studies have demonstrated that exercise can influence motor skill learning. However, the specific components of learning primed by exercise remain unclear. This study examined the effect of a preceding bout of high intensity interval training (HIIT) on the acquisition of a novel motor skill. The investigation focused on whether improvement in skill across the session was attributable to online gains during active practice or offline rest periods between practice blocks. There was also exploration as to whether common polymorphisms of the BDNF and DRD2/ANKK1 genes that regulate plasticity, learning, and memory, influenced the relationship between exercise and motor learning. It was demonstrated that HIIT enhanced skill acquisition, but that the effects of HIIT priming were not specifically attributable to within-session online or offline learning processes. Contrary to research on overnight consolidation, there was no interaction between BDNF, nor DRD2/ANKK1 genotype, with exercise primed skill learning.

neuroscience↗

Identification and performance of environmentally-driven recruitment relationships in state space assessment models

Environmentally-driven recruitment relationships are important for understanding fisheries responses to climate change; however they are difficult to estimate due in part to large variability in the recruitment process. State space models provide a promising way forward in allowing the characterization of multiple sources of stochastic variability. Here we conducted a large simulation-estimation study using environmentally-driven recruitment relationships to evaluate the effects of operating model characteristics on state space assessment model performance. We generally find low parameter and assessment bias across operating and estimating model combinations; however, some assessment and parameter bias is present under conditions of high recruitment variability and low spawning stock biomass contrast. Model identifiability for the correct functional form of the stock recruit relationship and the environmental relationship was generally poor, and projections were insensitive to assumed values of the environmental driver. We recommend the use of random effects on recruitment in state space assessments and caution against explicit stock-recruitment relationships. We encourage future work on environmental nonstationarity, which will be of increasing importance as exploited fish stocks experience accelerating rates of environmental change.

ecology↗

Default mode and motor networks facilitate early learning of implicit motor sequences: a multimodal MR spectroscopy and fMRI study

Learning new motor skills is a fundamental process that involves the sequencing of actions. Skill develops with practice and time, and manifests as performance that is fast and accurate. Although we know that learning can occur through an implicit process in the absence of conscious awareness, and across multiple temporal scales, the precise neural mechanisms mediating implicit motor sequence learning remain poorly understood. Similarly, the capacity for interventions with known influence on learning and memory, such as cardiovascular exercise, to facilitate implicit learning is yet to be clearly established. Here, we investigated the neuroplasticity of implicit motor sequence learning and the effect of acute exercise priming. Healthy adults (39.5% female) aged 22.55 {+/-} 2.69 years were allocated to either a high-intensity exercise (HIIT) group (n = 16) or to a very low-intensity control group (n = 17). Following exercise, participants performed a serial reaction time task. MR spectroscopy estimates of sensorimotor gamma-aminobutyric acid (GABA) were acquired before and after exercise, and during task performance, and resting-state fMRI was acquired at the end of the protocol. We show that early stages of learning are linked to default mode network connectivity, while the overall degree of learning following sustained practice is associated with motor network connectivity. Sensorimotor GABA concentration was linked to the early stages of learning, and GABA concentration was modulated following HIIT, although the two were not related. Overall, via integration of multiple neuroimaging modalities we demonstrate that interactions between hippocampal and motor networks underlie implicit motor sequence learning. Key points summary- Motor learning occurs across different temporal scales and can arise implicitly in the absence of conscious awareness. - Explicit motor learning is linked to the brains primary inhibitory neurotransmitter, GABA, and interactions across motor and hippocampal networks. - Whether these same neural mechanisms are implicated in implicit learning is unclear. Similarly, the capacity to influence learning via priming with cardiovascular exercise is yet to be clearly established. - We show that early implicit learning is underpinned by default mode network connectivity and sensorimotor GABA concentration, while total learning following sustained practice is linked to motor network connectivity. We also found that HIIT exercise elevated sensorimotor GABA concentration, but not the magnitude of implicit learning. - Overall, our results highlight shared involvement of default mode and motor networks in implicit motor sequence learning.

neuroscience↗

The JNK and Hippo pathways control epithelial integrity and prevent tumour initiation by regulating an overlapping transcriptome

Epithelial organs maintain their integrity and prevent tumour initiation by actively removing defective cells, such as those that have lost apicobasal polarity. Here, we identify how transcription factors of two key signalling pathways - Jun-N-terminal kinase (JNK) and Hippo - regulate epithelial integrity by controlling transcription of an overlapping set of target genes. Targeted DamID experiments reveal that in proliferating cells of the Drosophila melanogaster eye, the AP-1 transcription factor Jun, and the Hippo pathway transcription regulators Yorkie and Scalloped bind to a common suite of target genes that regulate organ growth. In defective neoplastic cells, AP-1 transcription factors repress transcription of growth genes together with the CtBP co-repressor. If gene repression by AP-1/CtBP fails, neoplastic tumour growth ensues, driven by Yorkie/Scalloped. Thus, AP-1/CtBP eliminates defective cells and prevents tumour initiation by acting in parallel to Yorkie/Scalloped to repress expression of a shared transcriptome. These findings shed new light on the maintenance of epithelial integrity and tumour suppression.

developmental biology↗

Timing and Amplitude of Catch-up Saccades to Accelerating Targets

To track moving targets, humans move their eyes using both saccades and smooth pursuit. If pursuit eye movements fail to accurately track the moving target, catch-up saccades are initiated to rectify the tracking error. It is well known that retinal position and velocity errors determine saccade timing and amplitude, but the extent to which retinal acceleration error influences these aspects is not well quantified. To test this, 13 adult human participants performed an experiment where they pursued accelerating / decelerating targets. During ongoing pursuit, we introduced a randomly sized target step to evoke a catch-up saccade and analyzed its timing and amplitude. We observed that retinal acceleration error was a statistically significant predictor of saccade amplitude and timing. A multiple linear regression supported our hypothesis that retinal acceleration errors influence saccade amplitude in addition to the influence of retinal position and velocity errors. We also found that saccade latencies were shorter when retinal acceleration error increased the tracking error and vice versa. In summary, our findings support a model in which retinal acceleration error is used to compute a predicted position error [~]100ms into the future to trigger saccades and determine saccade amplitude. Significance statementWhen visually tracking object motion, humans combine smooth pursuit and saccadic eye movements to maintain the target image on the fovea. Retinal position and velocity errors are known to determine catch-up saccade amplitude and timing, however it is unknown if retinal acceleration error is also used to predict future target position. This study provides evidence of a small but statistically significant contribution of retinal acceleration error in determining saccade amplitude and timing.

neuroscience↗

Rare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogenic organisms may translocate from the gut microbiome into the bloodstream to cause infections, the mechanisms by which HCT patients acquire pathogens in their microbiome have not yet been described. We hypothesized that patient-patient transmission may be responsible for pathogens colonizing the microbiome of HCT patients, and that patients who share time and space in the hospital are more likely to share bacterial strains. Here, we used linked-read and short-read metagenomic sequencing to analyze 401 stool samples collected from 149 adults undergoing HCT and hospitalized in the same unit over five years. We used metagenomic assembly and strain-specific comparison methods to investigate transmission of gut microbiota between individuals. While patients who shared time and space in the hospital did not converge in overall microbiome composition, we did observe four pairs of patients who harbor identical or nearly identical E. faecium strains in their microbiome. These strains may be the result of transmission between patients who shared a room and bathroom, acquisition from a common source in the hospital or transmission from an unsampled source. We also observed identical Akkermansia muciniphila and Hungatella hathewayi strains in two pairs of patients. In both cases, the patients were roommates for at least one day, the strain was absent in the putative recipients microbiome prior to the period of roommate overlap and the putative recipient had a microbiome perturbed by antibiotic treatment for a bloodstream infection. Finally, we identified multiple patients who harbored identical strains of several species commonly found in commercial probiotics and dairy products, including Lactobacillus rhamnosus, Lactobacillus gasseri and Streptococcus thermophilus. Overall, our findings indicate that pathogenic organisms from a single source are not frequently colonizing the gut microbiome of multiple patients. However, the potential transmission of commensal microbes with immunomodulatory properties raises questions about the recovery of microbiome diversity after HCT, and indicates that patients in this setting may acquire new microbes by sharing space with others.

microbiology↗

Design, construction, and deployment of an affordable and long-lasting moored deep-water fish aggregation device

Fish aggregation devices (FADs) are used worldwide to enhance the efficiency of various fisheries. Devices consist of a floating or subsurface component designed to exploit natural fish behavior, using species attraction to structure (e.g., Sargassum spp.) to aggregate fish and increase capture success in open ocean environments. Concerns have arisen regarding the scale and management of FAD-associated fisheries, however, the efficiency of FADs to aggregate fish also introduces the possibility for FADs to be used as conservation tools to study pelagic species ecology. Building on two successful and several failed deployments of anchored deep-water (>500 m) subsurface (10 m) FADs over three years in The Bahamas, and observations from the subsequent FAD monitoring program, the objectives of the paper are to: 1) provide details and considerations for the design, construction, and deployment of an affordable and durable deep-water subsurface FAD that can be deployed using small boats; and 2) highlight the potential for a long-lasting moored FAD to be used as a sustainable and reliable scientific platform for pelagic species research and conservation, lending specifically to several research applications. This information will be useful for assessing the impacts that FADs and other anthropogenic marine infrastructure have on wild marine species, and their efficacy for conserving pelagic fish through increased encounters for study.

ecology↗

SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis

Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19.

immunology↗

The microbiome mediates subchondral bone loss and metabolomic changes after acute joint trauma

ObjectiveTo compare the early responses to joint injury in conventional and germ-free mice. DesignPost traumatic osteoarthritis PTOA was induced using a non-invasive anterior cruciate ligament rupture model in 20-week old germ-free (GF) and conventional C57BL/6 mice. Injury was induced in the left knees of n=8 GF and n=10 conventional mice. To examine the effects of injury, n=5 GF and n=9 conventional control mice were used. Mice were euthanized seven days post-injury, followed by synovial fluid recovery for global metabolomic profiling and analysis of epiphyseal trabecular bone by micro-computed tomography (CT). Global metabolomic profiling assessed metabolic differences in the joint response to injury between GF and conventional mice. Magnitude of trabecular bone volume loss measured using CT assessed early OA progression in GF and conventional mice. ResultsCT found that GF mice had significantly less trabecular bone loss compared to conventional mice, indicating that the GF status was protective against early OA changes in bone structure. Global metabolomic profiling showed that conventional mice had greater variability in their metabolic response to injury, and a more distinct joint metabolome compared to their corresponding controls. Furthermore, differences in the response to injury in GF compared to conventional mice were linked to mouse metabolic pathways that regulate inflammation associated with the innate immune system. ConclusionsThese results suggest that the gut microbiota promote the development of PTOA during the acute phase following joint trauma possibly through the regulation of the innate immune system.

immunology↗

Dissecting the toxicity and mitigating the impact of harmful Prymnesium blooms in the UK waters of the Norfolk Broads

Prymnesium parvum is a toxin-producing microalga that causes harmful algal blooms (HABs) globally, frequently leading to massive fish kills that have adverse ecological and economic implications for natural waterways and aquaculture alike. The dramatic effects observed on fish are likely due to algae-produced polyether toxins, known as the prymnesins, but these compounds had not been detected in environmental samples, which has resulted in ambiguity about the true ichthyotoxic entities. Using qPCR, we found elevated levels of both P. parvum and its lytic virus, PpDNAV-BW1, in a fish-killing bloom on the Norfolk Broads, United Kingdom, in March 2015, a site historically plagued by P. parvum blooms. 16S rRNA gene sequencing confirmed that P. parvum dominated the bloom microbial community and that the microbial species diversity changed after recovery of the ecosystem. We also detected, for the first time, the recently discovered B-type prymnesin toxins in Broads waterway samples and gill tissue isolated from a dead fish taken from the study site. Furthermore, Norfolk Broads P. parvum isolates unambiguously produced B-type toxins in laboratory-grown cultures. In addition, a 2-year longitudinal study of the Broads study site showed P. parvum blooms positively correlated with increased temperature and that PpDNAV plays a significant role in P. parvum bloom demise in this natural setting. Finally, we used a field trial to show that treatment with low doses of hydrogen peroxide represents an effective strategy to mitigate blooms of P. parvum in enclosed water bodies.

microbiology↗