Biology subjects

Noble, C.

Publications and source records attributed to Noble, C..

9 recordsLinked to original sources

bioRxiv2026

Semaglutide promotes intramuscular fat formation after injury

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become defining therapies in the management of type 2 diabetes and obesity. Despite recent interest in the effects of GLP-1RA therapy on skeletal muscle, their influence on muscle repair after injury remains largely untested. Because GLP-1RA use is common in populations at heightened risk for diminished regenerative capacity, a critical unanswered question is whether GLP-1R agonism supports muscle regeneration or alters the normal course of recovery after injury. Using intramuscular glycerol injection as an adipogenic injury model, we assessed whether semaglutide, a widely prescribed GLP-1RA, alters the balance between myogenesis and adipogenesis during regeneration. Surprisingly, semaglutide treatment markedly increased the formation of intramuscular adipose tissue (IMAT) and inhibited the growth of regenerated fibers. These effects were injury-dependent, as uninjured muscle showed no detectable differences in IMAT or myofiber size. Together, these findings identify a previously underappreciated context in which GLP-1RA therapy may adversely affect muscle quality.

developmental biology↗

bioRxiv2025

FishProx: Proximate conspecific interaction of Atlantic salmon (Salmo salar) for behavioural analysis through instance segmentation masks

In modern fish production and experimental facilities, camera installations are increasingly common for monitoring animal welfare. This opens up a new alley of autonomous tracking systems levering streamed data. However, the substantial amount of data necessitates condensation for human operators. In this paper, we present the out-of-the-box pipeline called FishProx that starts with the imagery of fish in tanks and ends in the calculation of welfare impacting factors through anomaly scores. The utilisation of the Segment Anything Model (SAM) is the basis for the identification of feeding behaviour and also (ab)normal behaviour through analysing snapshots of the fish tanks to infer metrics such as fish cohesion and cluster alignment, alongside the detection count. Our method employs automatic and robust algorithms for camera systems, making additional labelled data unnecessary, thereby saving energy and costs. Furthermore, automatic fish observation coupled with integrated analytical capabilities can lead to a sensible autonomous decision-making process. Lastly, by providing objective metrics, our approach might guide the enabling of automatic quantification of fish states, making comparative studies possible.

animal behavior and cognition↗

bioRxiv2025

Seeing through the Static: Reduced Imagery Vividness in Aphantasia is Associated with Impaired Temporal Lobe Signal Complexity

Aphantasia is the inability to experience mental imagery in full wakefulness without any prominent perceptual deficits. Visual aphantasia is associated with differences in distributed brain networks, but its neurobiological underpinnings remain a mystery. We rationalised that aphantasia may arise due to impairments in the top-down control over visual imagination. We expected that this in turn would prevent the brains of aphantasic subjects from differentiating neural activity encoding the contents of imagination from the background noise of resting activity, particularly within the ventral temporal lobes. To test this hypothesis, we re-analysed functional magnetic resonance imaging data collected from aphantasics (n = 23) and controls (n = 20) during a simple perception and imagery task. We used two measures of informational complexity to quantify the complexity of the spatial pattern of thresholded BOLD signal in the participants temporal lobes during visual imagery. This spatial complexity was lower in aphantasics than controls during blocks of imagery, but not during perception (P < 0.05). We then performed dynamic functional connectivity analyses on the same data to demonstrate that the higher-order networks of aphantasics coupled abnormally with the temporal lobes during imagery (P < 0.05). These results provide a novel perspective, reframing aphantasia as an inability of the visual system to selectively activate regions encoding object-specific visual categories above background levels of noise.

neuroscience↗

bioRxiv2022

Metadata preservation and stewardship for genomic data is possible, but must happen now

Genetic diversity within species represents a fundamental yet underappreciated level of biodiversity. Because genetic diversity can indicate species and population resilience to changing climate, its measurement is relevant to many national and global conservation policy targets. Many studies of evolutionary biology, molecular ecology and conservation genetics produce large amounts of genome-scale genetic diversity data for wild populations. While open data policies have ensured an abundance of freely available genomic data stored in the databases of the International Nucleotide Sequence Database Collaboration (INSDC), only about 13% of current accessions have the associated spatial and temporal metadata in INSDC necessary to be reused in monitoring programs, macrogenetic studies, or for acknowledging the sovereignty of nations or Indigenous Peoples. We undertook a "distributed datathon" to quantify the availability of these missing metadata in sources external to the INSDC and to test the hypothesis that these metadata decay with time. We also worked to remediate these missing metadata by extracting them, when present, from associated published papers, online repositories, and/or from direct communication with authors. Starting with 848 programmatically identified candidate datasets (INSDC BioProjects), we manually determined that 561 contained samples from wild populations. We successfully restored spatiotemporal metadata (locality name and/or geospatial coordinates and collection year) for 78% of these 561 datasets (N = 440 BioProjects comprising 45,105 individuals or BioSamples from 762 species in 17 phyla). We also quantified the availability of 33 additional categories of metadata in sources external to the INSDC. Information about associated publications and the type of habitat from which the samples were taken was the most easily found; information about sampling permits was the most challenging to locate. Looking at papers and online repositories was much more fruitful than contacting authors, who only replied to our email requests 45% of the time. Overall, 23% of our email queries to authors discovered useful metadata. Importantly, we found that the probability of retrieving spatiotemporal metadata declines significantly with the age of the dataset, with a 13.5% yearly decrease for metadata located in published papers or online repositories and up to a 22% yearly decrease for metadata that were only available from authors. This observable metadata decay, mirrored in studies of other types of biological data, should motivate swift updates to data sharing policies and researcher practices to ensure that the valuable context provided by metadata is not lost forever.

bioinformatics↗

bioRxiv2020

A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

The spread of SARS-CoV-2 has caused a global pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection, and may enable the relaxation of social distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection, therefore it is desirable that any new vaccine candidates should elicit a robust immune response in older adults. Here, we test the immunogenicity of the adenoviral vectored vaccine ChAdOx1 nCoV-19 (AZD-1222) in aged mice. We find that a single dose of this vaccine induces cellular and humoral immunity in aged mice, but at a reduced magnitude than in younger adult mice. Furthermore, we report that a second dose enhances the immune response to this vaccine in aged mice, indicating that a primeboost strategy may be a rational approach to enhance immunogenicity in older persons.

immunology↗

bioRxiv2019

Low Replication Capacity Virus Is Preferentially Transmitted In Mother-To-Child-Transmission But Not In Adult-To-Adult-Transmission Of HIV-1

Previous studies of the transmitted/founder virus compared to viral quasispecies in the donor have yielded conflicting results. In heterosexual adult-to-adult transmission (ATAT), the viral replicative capacity (VRC) of transmitted virus is reportedly either similar to, or somewhat higher than, that of donor virus, whilst transmitted virus in mother-to-child transmission (MTCT) has a significantly lower VRC than that of maternal virus. These discrepancies may be explained by the different methodologies used in these studies, or they may reflect true differences in the transmission bottleneck. To resolve this question, we here use the same methodology to compare transmitted versus donor virus in MTCT and ATAT. We show that, in a South African mother-child cohort, infant virus samples obtained at 1-2 days after birth had VRC significantly lower than in the mothers (p=0.0003). By contrast, in Zambian ATAT transmission pairs, VRC of transmitted virus was similar to or somewhat higher than donor virus (p=ns). The VRC of virus transmitted to the recipient, compared to that in the donor, was significantly lower in MTCT versus heterosexual ATAT (p=0.01). These studies demonstrate that fundamental differences exist between the viruses transmitted via the MTCT and ATAT bottlenecks that are not explained by methodological factors. This result is of importance since transmission of low replicative capacity virus results in low immune activation and a small viral reservoir, and therefore the preferential transmission of low fitness viruses in MTCT might be expected to increase cure potential in in utero infected infants and children.\n\nIMPORTANCEUnderstanding the factors determining which viruses are preferentially transmitted in HIV infection is critical to the development of new, effective strategies to prevent transmission. Despite this, much remains unknown in this respect, both with regard to adult-to-adult transmission (ATAT) but especially with respect to mother-to-child transmission (MTCT). The finding here that fundamental differences exist in the genetic bottleneck of HIV transmission between heterosexual ATAT and MTCT is an important initial step to help define the viral mechanisms contributing to transmission in each case. In addition, we show that viruses of low viral replicative capacity are preferentially transmitted in MTCT. This suggests the possibility that a window of opportunity exists following in utero infection in which early anti-viral intervention not only reduces the size and diversity of the viral reservoir, but additionally maintains a reservoir comprising low viral replicative capacity HIV. Low replicative capacity of transmitted virus has previously been shown to result in low immune activation and low proviral DNA load in central memory cells, factors likely to be directly relevant to increasing cure potential in HIV-infected infants and children.

immunology↗

bioRxiv2017

Current CRISPR gene drive systems are likely to be highly invasive in wild populations

Recent reports have suggested that CRISPR-based gene drives are unlikely to invade wild populations due to drive-resistant alleles that prevent cutting. Here we develop mathematical models based on existing empirical data to explicitly test this assumption. We show that although resistance prevents drive systems from spreading to fixation in large populations, even the least effective systems reported to date are highly invasive. Releasing a small number of organisms often causes invasion of the local population, followed by invasion of additional populations connected by very low gene flow rates. Examining the effects of mitigating factors including standing variation, inbreeding, and family size revealed that none of these prevent invasion in realistic scenarios. Highly effective drive systems are predicted to be even more invasive. Contrary to the National Academies report on gene drive, our results suggest that standard drive systems should not be developed nor field-tested in regions harboring the host organism.

synthetic biology↗

bioRxiv2017

Daisy quorum drives for the genetic restoration of wild populations

An ideal gene drive system to alter wild populations would 1) exclusively affect organisms within the political boundaries of consenting communities, and 2) be capable of restoring any engineered population to its original genetic state. Here we describe daisy quorum drive systems that meet these criteria by combining daisy drive with underdominance. A daisy quorum drive system is predicted to spread through a population until all of its daisy elements have been lost, at which point its fitness becomes frequency-dependent: mostly altered populations become fixed for the desired change, while engineered genes at low frequency are swiftly eliminated by natural selection. The result is an engineered population surrounded by wild-type organisms with limited mixing at the boundary. Releasing large numbers of wild-type organisms or a few bearing a population suppression element can reduce the engineered population below the quorum, triggering elimination of all engineered sequences. In principle, the technology can restore any drive-amenable population carrying engineered genes to wild-type genetics. Daisy quorum systems may enable efficient, community-supported, and genetically reversible ecological engineering.\n\nSummaryLocal communities should be able to control their own environments without forcing those choices on others. Ideally, each community could reversibly alter local wild organisms in ways that cannot spread beyond their own boundaries, and any engineered population could be restored to its original genetic state. We've invented a 'daisy quorum' drive system that appears to meet these criteria.\n\n\"Daisy\" refers to a daisy drive, which typically uses a daisy-chain of linked genes to spread a change through a local population while losing links every generation until it stops spreading. \"Quorum\" reflects the system's ability to \"vote\" on whether a local population should be altered or not: once all daisy elements are lost, it favors replication by the altered version or the original depending on which is more abundant in the local area. Put together, they result in a change that first spreads through a local population, then either becomes locally prevalent is eliminating, inhibiting mixing at the boundary. All organisms in the target population are altered, but changes are unable to spread much beyond that area due to being greatly outnumbered by wild-type organisms and consequently less able to replicate.\n\nWe haven't yet performed any experiments involving daisy quorum systems. Rather, were describing what we intend to do, including the safeguards we will use and our assessment of risks, in the hope that others will evaluate our plans and tell us if there's anything wrong that we missed. We hope that all researchers working on gene drive systems - and other technologies that could impact the shared environment - will similarly pre-register their plans. Sharing plans can reduce needless duplication, accelerate progress, and make the proposed work safer for everyone.

synthetic biology↗

bioRxiv2017

Daisyfield gene drive systems harness repeated genomic elements as a generational clock to limit spread

Methods of altering wild populations are most useful when inherently limited to local geographic areas. Here we describe a novel form of gene drive based on the introduction of multiple copies of an engineered daisy sequence into repeated elements of the genome. Each introduced copy encodes guide RNAs that target one or more engineered loci carrying the CRISPR nuclease gene and the desired traits. When organisms encoding a drive system are released into the environment, each generation of mating with wild-type organisms will reduce the average number of the guide RNA elements per daisyfield organism by half, serving as a generational clock. The loci encoding the nuclease and payload will exhibit drive only as long as a single copy remains, placing an inherent limit on the extent of spread.

synthetic biology↗