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1.
J Neurophysiol ; 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38863427

ABSTRACT

Everyday actions like moving the head, walking around and grasping objects are typically self-controlled. This presents a problem when studying the signals encoding such actions because active self-movement is difficult to control experimentally. Available techniques demand repeatable trials, but each action is unique, making it difficult to measure fundamental properties like psychophysical thresholds. We present a novel paradigm that recovers both precision and bias of self-movement signals with minimal constraint on the participant. The paradigm relies on linking image motion to previous self-movement, and two experimental phases to extract the signal encoding the latter. The paradigm takes care of a hidden source of external noise not previously accounted for in techniques that link display motion to self-movement in real time (e.g. virtual reality). We use head rotations as an example of self-movement, and show that the precision of the signals encoding head movement depends on whether they are being used to judge visual motion or auditory motion. We find that perceived motion is slowed during head movement in both cases. The 'non-image' signals encoding active head rotation (motor commands, proprioception and vestibular cues) are therefore biased towards lower speeds and/or displacements. In a second experiment, we trained participants to rotate their heads at different rates and found that the imprecision of the head rotation signal rises proportionally with head speed (Weber's Law). We discuss the findings in terms of the different motion cues used by vision and hearing, and the implications they have for Bayesian models of motion perception.

2.
G3 (Bethesda) ; 13(10)2023 09 30.
Article in English | MEDLINE | ID: mdl-37548242

ABSTRACT

It is estimated that animals pollinate 87.5% of flowering plants worldwide and that managed honey bees (Apis mellifera) account for 30-50% of this ecosystem service to agriculture. In addition to their important role as pollinators, honey bees are well-established insect models for studying learning and memory, behavior, caste differentiation, epigenetic mechanisms, olfactory biology, sex determination, and eusociality. Despite their importance to agriculture, knowledge of honey bee biology lags behind many other livestock species. In this study, we have used scRNA-Seq to map cell types to different developmental stages of the worker honey bee (prepupa at day 11 and pupa at day 15) and sought to determine their gene expression signatures. To identify cell-type populations, we examined the cell-to-cell network based on the similarity of the single-cells transcriptomic profiles. Grouping similar cells together we identified 63 different cell clusters of which 17 clusters were identifiable at both stages. To determine genes associated with specific cell populations or with a particular biological process involved in honey bee development, we used gene coexpression analysis. We combined this analysis with literature mining, the honey bee protein atlas, and gene ontology analysis to determine cell cluster identity. Of the cell clusters identified, 17 were related to the nervous system and sensory organs, 7 to the fat body, 19 to the cuticle, 5 to muscle, 4 to compound eye, 2 to midgut, 2 to hemocytes, and 1 to malpighian tubule/pericardial nephrocyte. To our knowledge, this is the first whole single-cell atlas of honey bees at any stage of development and demonstrates the potential for further work to investigate their biology at the cellular level.


Subject(s)
Ecosystem , Transcriptome , Bees/genetics , Animals , Pupa/genetics
3.
Proc Natl Acad Sci U S A ; 119(50): e2211217119, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36469788

ABSTRACT

Most new pathogens of humans and animals arise via switching events from distinct host species. However, our understanding of the evolutionary and ecological drivers of successful host adaptation, expansion, and dissemination are limited. Staphylococcus aureus is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide. Here we trace the evolutionary history of bovine S. aureus using a global dataset of 10,254 S. aureus genomes including 1,896 bovine isolates from 32 countries in 6 continents. We identified 7 major contemporary endemic clones of S. aureus causing bovine mastitis around the world and traced them back to 4 independent host-jump events from humans that occurred up to 2,500 y ago. Individual clones emerged and underwent clonal expansion from the mid-19th to late 20th century coinciding with the commercialization and industrialization of dairy farming, and older lineages have become globally distributed via established cattle trade links. Importantly, we identified lineage-dependent differences in the frequency of host transmission events between humans and cows in both directions revealing high risk clones threatening veterinary and human health. Finally, pangenome network analysis revealed that some bovine S. aureus lineages contained distinct sets of bovine-associated genes, consistent with multiple trajectories to host adaptation via gene acquisition. Taken together, we have dissected the evolutionary history of a major endemic pathogen of livestock providing a comprehensive temporal, geographic, and gene-level perspective of its remarkable success.


Subject(s)
Staphylococcal Infections , Staphylococcus aureus , Female , Humans , Cattle , Animals , Staphylococcus aureus/genetics , Livestock/genetics , Staphylococcal Infections/epidemiology , Staphylococcal Infections/veterinary , Staphylococcal Infections/genetics , Genome , Host Specificity
4.
J Acoust Soc Am ; 152(4): 2140, 2022 10.
Article in English | MEDLINE | ID: mdl-36319254

ABSTRACT

Human sound localization in the horizontal dimension is thought to be dominated by binaural cues, particularly interaural time delays, because monaural localization in this dimension is relatively poor. Remaining ambiguities of front versus back and up versus down are distinguished by high-frequency spectral cues generated by the pinna. The experiments in this study show that this account is incomplete. Using binaural listening throughout, the pinna substantially enhanced horizontal discrimination in the frontal hemifield, making discrimination in front better than discrimination at the rear, particularly for directions away from the median plane. Eliminating acoustic effects of the pinna by acoustically bypassing them or low-pass filtering abolished the advantage at the front without affecting the rear. Acoustic measurements revealed a pinna-induced spectral prominence that shifts smoothly in frequency as sounds move from 0° to 90° azimuth. The improved performance is discussed in terms of the monaural and binaural changes induced by the pinna.


Subject(s)
Sound Localization , Humans , Acoustic Stimulation , Auditory Perception , Ear, External , Cues
5.
Vision Res ; 201: 108124, 2022 12.
Article in English | MEDLINE | ID: mdl-36193604

ABSTRACT

To account for perceptual bias, Bayesian models use the precision of early sensory measurements to weight the influence of prior expectations. As precision decreases, prior expectations start to dominate. Important examples come from motion perception, where the slow-motion prior has been used to explain a variety of motion illusions in vision, hearing, and touch, many of which correlate appropriately with threshold measures of underlying precision. However, the Bayesian account seems defeated by the finding that moving objects appear faster in the dark, because most motion thresholds are worse at low luminance. Here we show this is not the case for speed discrimination. Our results show that performance improves at low light levels by virtue of a perceived contrast cue that is more salient in the dark. With this cue removed, discrimination becomes independent of luminance. However, we found perceived speed still increased in the dark for the same observers, and by the same amount. A possible interpretation is that motion processing is therefore not Bayesian, because our findings challenge a key assumption these models make, namely that the accuracy of early sensory measurements is independent of basic stimulus properties like luminance. However, a final experiment restored Bayesian behaviour by adding external noise, making discrimination worse and slowing perceived speed down. Our findings therefore suggest that motion is processed in a Bayesian fashion but based on noisy sensory measurements that also vary in accuracy.


Subject(s)
Illusions , Motion Perception , Humans , Bias , Contrast Sensitivity
6.
BMC Bioinformatics ; 23(1): 416, 2022 Oct 08.
Article in English | MEDLINE | ID: mdl-36209064

ABSTRACT

BACKGROUND: The advent of low cost, high throughput DNA sequencing has led to the availability of thousands of complete genome sequences for a wide variety of bacterial species. Examining and interpreting genetic variation on this scale represents a significant challenge to existing methods of data analysis and visualisation. RESULTS: Starting with the output of standard pangenome analysis tools, we describe the generation and analysis of interactive, 3D network graphs to explore the structure of bacterial populations, the distribution of genes across a population, and the syntenic order in which those genes occur, in the new open-source network analysis platform, Graphia. Both the analysis and the visualisation are scalable to datasets of thousands of genome sequences. CONCLUSIONS: We anticipate that the approaches presented here will be of great utility to the microbial research community, allowing faster, more intuitive, and flexible interaction with pangenome datasets, thereby enhancing interpretation of these complex data.


Subject(s)
Genome, Bacterial , High-Throughput Nucleotide Sequencing , Bacteria/genetics , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods
7.
PLoS Comput Biol ; 18(7): e1010310, 2022 07.
Article in English | MEDLINE | ID: mdl-35877685

ABSTRACT

Graphia is an open-source platform created for the graph-based analysis of the huge amounts of quantitative and qualitative data currently being generated from the study of genomes, genes, proteins metabolites and cells. Core to Graphia's functionality is support for the calculation of correlation matrices from any tabular matrix of continuous or discrete values, whereupon the software is designed to rapidly visualise the often very large graphs that result in 2D or 3D space. Following graph construction, an extensive range of measurement algorithms, routines for graph transformation, and options for the visualisation of node and edge attributes are available, for graph exploration and analysis. Combined, these provide a powerful solution for the interpretation of high-dimensional data from many sources, or data already in the form of a network or equivalent adjacency matrix. Several use cases of Graphia are described, to showcase its wide range of applications in the analysis biological data. Graphia runs on all major desktop operating systems, is extensible through the deployment of plugins and is freely available to download from https://graphia.app/.


Subject(s)
Algorithms , Software
8.
Front Med (Lausanne) ; 8: 740615, 2021.
Article in English | MEDLINE | ID: mdl-34616758

ABSTRACT

Bone is now regarded to be a key regulator of a number of metabolic processes, in addition to the regulation of mineral metabolism. However, our understanding of complex bone metabolic interactions at a systems level remains rudimentary. in vitro molecular biology and bioinformatics approaches have frequently been used to understand the mechanistic changes underlying disease at the cell level, however, these approaches lack the capability to interrogate dynamic multi-bone metabolic interactions in vivo. Here we present a novel and integrative approach to understand complex bone metabolic interactions in vivo using total-body positron emission tomography (PET) network analysis of murine 18F-FDG scans, as a biomarker of glucose metabolism in bones. In this report we show that different bones within the skeleton have a unique glucose metabolism and form a complex metabolic network, which could not be identified using single tissue simplistic PET standard uptake values analysis. The application of our approach could reveal new physiological and pathological tissue interactions beyond skeletal metabolism, due to PET radiotracers diversity and the advent of clinical total-body PET systems.

9.
Brief Bioinform ; 22(2): 1848-1859, 2021 03 22.
Article in English | MEDLINE | ID: mdl-32313939

ABSTRACT

The fast accumulation of biological data calls for their integration, analysis and exploitation through more systematic approaches. The generation of novel, relevant hypotheses from this enormous quantity of data remains challenging. Logical models have long been used to answer a variety of questions regarding the dynamical behaviours of regulatory networks. As the number of published logical models increases, there is a pressing need for systematic model annotation, referencing and curation in community-supported and standardised formats. This article summarises the key topics and future directions of a meeting entitled 'Annotation and curation of computational models in biology', organised as part of the 2019 [BC]2 conference. The purpose of the meeting was to develop and drive forward a plan towards the standardised annotation of logical models, review and connect various ongoing projects of experts from different communities involved in the modelling and annotation of molecular biological entities, interactions, pathways and models. This article defines a roadmap towards the annotation and curation of logical models, including milestones for best practices and minimum standard requirements.


Subject(s)
Computational Biology/methods , Models, Biological , Practice Guidelines as Topic , Reproducibility of Results
10.
Immunother Adv ; 1(1): ltaa008, 2021 Jan.
Article in English | MEDLINE | ID: mdl-36284901

ABSTRACT

Introduction: Ageing is associated with increased number of infections, decreased vaccine efficacy and increased systemic inflammation termed inflammageing. These changes are reflected by reduced recall responses to varicella zoster virus (VZV) challenge in the skin of older adults. Vitamin D deficiency is more common in the old and has been associated with frailty and increased inflammation. In addition, vitamin D increases immunoregulatory mechanisms and therefore has the potential to inhibit inflammageing. Objectives: We investigated the use of vitamin D3 replacement to enhance cutaneous antigen-specific immunity in older adults (≥65 years). Methods: Vitamin D insufficient older adults (n = 18) were administered 6400IU of vitamin D3/day orally for 14 weeks. Antigen-specific immunity to VZV was assessed by clinical score assessment of the injection site and transcriptional analysis of skin biopsies collected from challenged injection sites pre- and post-vitamin D3 replacement. Results: We showed that older adults had reduced VZV-specific cutaneous immune response and increased non-specific inflammation as compared to young. Increased non-specific inflammation observed in the skin of older adults negatively correlated with vitamin D sufficiency. We showed that vitamin D3 supplementation significantly increased the response to cutaneous VZV antigen challenge in older adults. This enhancement was associated with a reduction in inflammatory monocyte infiltration with a concomitant enhancement of T cell recruitment to the site of antigen challenge in the skin. Conclusion: Vitamin D3 replacement can boost antigen-specific immunity in older adults with sub-optimal vitamin D status.

11.
Nat Aging ; 1(1): 101-113, 2021 01.
Article in English | MEDLINE | ID: mdl-37118005

ABSTRACT

We have previously shown that healthy older adults exhibit reduced cutaneous immune responses during a varicella zoster virus (VZV) antigen challenge that correlated with a nonspecific inflammatory response to the injection itself. Here we found that needle damage during intradermal injections in older adults led to an increase in the number of cutaneous senescent fibroblasts expressing CCL2, resulting in the local recruitment of inflammatory monocytes. These infiltrating monocytes secreted prostaglandin E2, which inhibited resident memory T cell activation and proliferation. Pretreatment of older participants with a p38 mitogen-activated protein kinase inhibitor in vivo decreased CCL2 expression and inhibited monocyte recruitment and secretion of prostaglandin E2. This coincided with an increased response to VZV antigen challenge in the skin. Our results point to a series of molecular and cellular mechanisms that link cellular senescence, tissue damage, excessive inflammation and reduced immune responsiveness in human skin and demonstrate that tissue-specific immunity can be restored in older adults by short-term inhibition of inflammatory responses.


Subject(s)
Dinoprostone , Monocytes , Humans , Aged , Dinoprostone/metabolism , Aging , Herpesvirus 3, Human , Lymphocyte Activation , Fibroblasts
12.
Sci Rep ; 10(1): 21047, 2020 12 03.
Article in English | MEDLINE | ID: mdl-33273621

ABSTRACT

Monocytes are among the major myeloid cells that respond to Toxoplasma, a ubiquitous foodborne that infects ≥ 1 billion people worldwide, in human peripheral blood. As such, a molecular understanding of human monocyte-Toxoplasma interactions can expedite the development of novel human toxoplasmosis control strategies. Current molecular studies on monocyte-Toxoplasma interactions are based on average cell or parasite responses across bulk cell populations. Although informative, population-level averages of monocyte responses to Toxoplasma have sometimes produced contradictory results, such as whether CCL2 or IL12 define effective monocyte responses to the parasite. Here, we used single-cell dual RNA sequencing (scDual-Seq) to comprehensively define, for the first time, the monocyte and parasite transcriptional responses that underpin human monocyte-Toxoplasma encounters at the single cell level. We report extreme transcriptional variability between individual monocytes. Furthermore, we report that Toxoplasma-exposed and unexposed monocytes are transcriptionally distinguished by a reactive subset of CD14+CD16- monocytes. Functional cytokine assays on sorted monocyte populations show that the infection-distinguishing monocytes secrete high levels of chemokines, such as CCL2 and CXCL5. These findings uncover the Toxoplasma-induced monocyte transcriptional heterogeneity and shed new light on the cell populations that largely define cytokine and chemokine secretion in human monocytes exposed to Toxoplasma.


Subject(s)
Monocytes/metabolism , Toxoplasmosis/metabolism , Transcriptome , Cells, Cultured , Humans , RNA-Seq , Receptors, IgG/genetics , Receptors, IgG/metabolism , Single-Cell Analysis , Toxoplasmosis/genetics
13.
Sci Rep ; 10(1): 10814, 2020 07 02.
Article in English | MEDLINE | ID: mdl-32616903

ABSTRACT

Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis. Mutations in components of these organelles or those involved in their assembly may result in a diverse set of diseases collectively known as ciliopathies. Accordingly, many cilia-associated proteins have been described, while those distinguishing cilia subtypes are poorly defined. Here we set out to define genes associated with motile cilia in humans based on their transcriptional signature. To define the signature, we performed network deconvolution of transcriptomics data derived from tissues possessing motile ciliated cell populations. For each tissue, genes coexpressed with the motile cilia-associated transcriptional factor, FOXJ1, were identified. The consensus across tissues provided a transcriptional signature of 248 genes. To validate these, we examined the literature, databases (CilDB, CentrosomeDB, CiliaCarta and SysCilia), single cell RNA-Seq data, and the localisation of mRNA and proteins in motile ciliated cells. In the case of six poorly characterised signature genes, we performed new localisation experiments on ARMC3, EFCAB6, FAM183A, MYCBPAP, RIBC2 and VWA3A. In summary, we report a set of motile cilia-associated genes that helps shape our understanding of these complex cellular organelles.


Subject(s)
Cilia/genetics , Forkhead Transcription Factors/genetics , Transcription, Genetic/genetics , Armadillo Domain Proteins , Calcium-Binding Proteins , Carrier Proteins , Cilia/physiology , Gene Expression , Humans , Membrane Proteins , Repressor Proteins
14.
Invest Ophthalmol Vis Sci ; 61(6): 15, 2020 06 03.
Article in English | MEDLINE | ID: mdl-32526031

ABSTRACT

Purpose: Infantile nystagmus (IN) presents with continuous, predominantly horizontal eye oscillations. It remains controversial whether those with IN have normal horizontal pursuit, while vertical pursuit has rarely been studied. We examined whether there are pursuit deficits associated with IN by investigating the effect of target direction, velocity, and amplitude. Methods: Twelve adults with idiopathic IN performed a pursuit task, a 0.4° dot moved either horizontally or vertically at 8 or 16°/s, through amplitudes of 8°, 16°, or 32°. Accuracy and precision errors were computed as bivariate probability density functions of target-relative eye velocities. Results: Eye velocity was less precise along the horizontal axis during both horizontal and vertical pursuit, reflecting the primary axis of the eye oscillation. Mean accuracy error along the target trajectory during vertical pursuit was just as impaired as during horizontal pursuit. There was a greater error in accuracy along the target trajectory for 16°/s targets than 8°/s. Finally, targets that oscillated at 2.0 Hz had a greater error in accuracy along the target trajectory than frequencies of 1.0 Hz or 0.5 Hz. When studied using the same experimental protocol, pursuit performance for typical observers was always better. Conclusions: These findings strongly support our hypothesis of severe deficits in pursuit accuracy in observers with IN for horizontally and vertically moving targets, as well as for targets that move at higher speeds or oscillate more quickly. Overall, IN pursuit impairment appears to have previously been underestimated, highlighting a need for further quantitative studies of dynamic visual function in those with IN.


Subject(s)
Genetic Diseases, X-Linked/physiopathology , Nystagmus, Congenital/physiopathology , Pursuit, Smooth/physiology , Adolescent , Adult , Aged , Eye Movements/physiology , Female , Humans , Male , Middle Aged , Motion Perception , Ophthalmoscopy , Reproducibility of Results , Slit Lamp Microscopy , Tomography, Optical Coherence , Young Adult
15.
Front Microbiol ; 11: 659, 2020.
Article in English | MEDLINE | ID: mdl-32362882

ABSTRACT

A network analysis including relative abundances of all ruminal microbial genera (archaea, bacteria, fungi, and protists) and their genes was performed to improve our understanding of how the interactions within the ruminal microbiome affects methane emissions (CH4). Metagenomics and CH4 data were available from 63 bovines of a two-breed rotational cross, offered two basal diets. Co-abundance network analysis revealed 10 clusters of functional niches. The most abundant hydrogenotrophic Methanobacteriales with key microbial genes involved in methanogenesis occupied a different functional niche (i.e., "methanogenesis" cluster) than methylotrophic Methanomassiliicoccales (Candidatus Methanomethylophylus) and acetogens (Blautia). Fungi and protists clustered together and other plant fiber degraders like Fibrobacter occupied a seperate cluster. A Partial Least Squares analysis approach to predict CH4 variation in each cluster showed the methanogenesis cluster had the best prediction ability (57.3%). However, the most important explanatory variables in this cluster were genes involved in complex carbohydrate degradation, metabolism of sugars and amino acids and Candidatus Azobacteroides carrying nitrogen fixation genes, but not methanogenic archaea and their genes. The cluster containing Fibrobacter, isolated from other microorganisms, was positively associated with CH4 and explained 49.8% of its variability, showing fermentative advantages compared to other bacteria and fungi in providing substrates (e.g., formate) for methanogenesis. In other clusters, genes with enhancing effect on CH4 were related to lactate and butyrate (Butyrivibrio and Pseudobutyrivibrio) production and simple amino acids metabolism. In comparison, ruminal genes negatively related to CH4 were involved in carbohydrate degradation via lactate and succinate and synthesis of more complex amino acids by γ-Proteobacteria. When analyzing low- and high-methane emitters data in separate networks, competition between methanogens in the methanogenesis cluster was uncovered by a broader diversity of methanogens involved in the three methanogenesis pathways and larger interactions within and between communities in low compared to high emitters. Generally, our results suggest that differences in CH4 are mainly explained by other microbial communities and their activities rather than being only methanogens-driven. Our study provides insight into the interactions of the rumen microbial communities and their genes by uncovering functional niches affecting CH4, which will benefit the development of efficient CH4 mitigation strategies.

16.
Schizophr Bull ; 46(2): 345-353, 2020 02 26.
Article in English | MEDLINE | ID: mdl-31219602

ABSTRACT

The dysconnection hypothesis of schizophrenia (SZ) proposes that psychosis is best understood in terms of aberrant connectivity. Specifically, it suggests that dysconnectivity arises through aberrant synaptic modulation associated with deficits in GABAergic inhibition, excitation-inhibition balance and disturbances of high-frequency oscillations. Using a computational model combined with a graded-difficulty visual orientation discrimination paradigm, we demonstrate that, in SZ, perceptual performance is determined by the balance of excitation-inhibition in superficial cortical layers. Twenty-eight individuals with a DSM-IV diagnosis of SZ, and 30 age- and gender-matched healthy controls participated in a psychophysics orientation discrimination task, a visual grating magnetoencephalography (MEG) recording, and a magnetic resonance spectroscopy (MRS) scan for GABA. Using a neurophysiologically informed model, we quantified group differences in GABA, gamma measures, and the predictive validity of model parameters for orientation discrimination in the SZ group. MEG visual gamma frequency was reduced in SZ, with lower peak frequency associated with more severe negative symptoms. Orientation discrimination performance was impaired in SZ. Dynamic causal modeling of the MEG data showed that local synaptic connections were reduced in SZ and local inhibition correlated negatively with the severity of negative symptoms. The effective connectivity between inhibitory interneurons and superficial pyramidal cells predicted orientation discrimination performance within the SZ group; consistent with graded, behaviorally relevant, disease-related changes in local GABAergic connections. Occipital GABA levels were significantly reduced in SZ but did not predict behavioral performance or oscillatory measures. These findings endorse the importance, and behavioral relevance, of GABAergic synaptic disconnection in schizophrenia that underwrites excitation-inhibition balance.


Subject(s)
Cerebral Cortex/metabolism , Cerebral Cortex/physiopathology , Discrimination, Psychological/physiology , Gamma Rhythm/physiology , Neural Inhibition/physiology , Schizophrenia/metabolism , Schizophrenia/physiopathology , gamma-Aminobutyric Acid/metabolism , Adult , Female , Humans , Interneurons/physiology , Magnetoencephalography , Male , Middle Aged , Pyramidal Cells/physiology , Space Perception/physiology , Visual Perception/physiology
17.
Microbiome ; 7(1): 149, 2019 Nov 18.
Article in English | MEDLINE | ID: mdl-31739805

ABSTRACT

Following publication of the original article [1], the authors reported an error in the Additional file 1.

18.
Front Vet Sci ; 6: 314, 2019.
Article in English | MEDLINE | ID: mdl-31620455

ABSTRACT

Tail amputation by tail docking or as an extreme consequence of tail biting in commercial pig production potentially has serious implications for animal welfare. Tail amputation causes peripheral nerve injury that might be associated with lasting chronic pain. The aim of this study was to investigate the short- and long-term effects of tail amputation in pigs on caudal DRG gene expression at different stages of development, particularly in relation to genes associated with nociception and pain. Microarrays were used to analyse whole DRG transcriptomes from tail amputated and sham-treated pigs 1, 8, and 16 weeks following tail treatment at either 3 or 63 days of age (8 pigs/treatment/age/time after treatment; n = 96). Tail amputation induced marked changes in gene expression (up and down) compared to sham-treated intact controls for all treatment ages and time points after tail treatment. Sustained changes in gene expression in tail amputated pigs were still evident 4 months after tail injury. Gene correlation network analysis revealed two co-expression clusters associated with amputation: Cluster A (759 down-regulated) and Cluster B (273 up-regulated) genes. Gene ontology (GO) enrichment analysis identified 124 genes in Cluster A and 61 genes in Cluster B associated with both "inflammatory pain" and "neuropathic pain." In Cluster A, gene family members of ion channels e.g., voltage-gated potassium channels (VGPC) and receptors e.g., GABA receptors, were significantly down-regulated compared to shams, both of which are linked to increased peripheral nerve excitability after axotomy. Up-regulated gene families in Cluster B were linked to transcriptional regulation, inflammation, tissue remodeling, and regulatory neuropeptide activity. These findings, demonstrate that tail amputation causes sustained transcriptomic expression changes in caudal DRG cells involved in inflammatory and neuropathic pain pathways.

19.
Transl Vis Sci Technol ; 8(5): 7, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31588372

ABSTRACT

PURPOSE: Small moving targets are followed by pursuit eye movements, with success ubiquitously defined by gain. Gain quantifies accuracy, rather than precision, and only for eye movements along the target trajectory. Analogous to previous studies of fixation, we analyzed pursuit performance in two dimensions as a function of target direction, velocity, and amplitude. As a subsidiary experiment, we compared pursuit performance against that of fixation. METHODS: Eye position was recorded from 15 observers during pursuit. The target was a 0.4° dot that moved across a large screen at 8°/s or 16°/s, either horizontally or vertically, through peak-to-peak amplitudes of 8°, 16°, or 32°. Two-dimensional eye velocity was expressed relative to the target, and a bivariate probability density function computed to obtain accuracy and precision. As a comparison, identical metrics were derived from fixation data. RESULTS: For all target directions, eye velocity was less precise along the target trajectory. Eye velocities orthogonal to the target trajectory were more accurate during vertical pursuit than horizontal. Pursuit accuracy and precision along and orthogonal to the target trajectory decreased at the higher target velocity. Accuracy along the target trajectory decreased with smaller target amplitudes. CONCLUSIONS: Orthogonal to the target trajectory, pursuit was inaccurate and imprecise. Compared to fixation, pursuit was less precise and less accurate even when following the stimulus that gave the best performance. TRANSLATIONAL RELEVANCE: This analytical approach may help the detection of subtle deficits in slow phase eye movements that could be used as biomarkers for disease progression and/or treatment.

20.
Front Genet ; 10: 701, 2019.
Article in English | MEDLINE | ID: mdl-31440274

ABSTRACT

The rumen microbiome is essential for the biological processes involved in the conversion of feed into nutrients that can be utilized by the host animal. In the present research, the influence of the rumen microbiome on feed conversion efficiency, growth rate, and appetite of beef cattle was investigated using metagenomic data. Our aim was to explore the associations between microbial genes and functional pathways, to shed light on the influence of bacterial enzyme expression on host phenotypes. Two groups of cattle were selected on the basis of their high and low feed conversion ratio. Microbial DNA was extracted from rumen samples, and the relative abundances of microbial genes were determined via shotgun metagenomic sequencing. Using partial least squares analyses, we identified sets of 20, 14, 17, and 18 microbial genes whose relative abundances explained 63, 65, 66, and 73% of the variation of feed conversion efficiency, average daily weight gain, residual feed intake, and daily feed intake, respectively. The microbial genes associated with each of these traits were mostly different, but highly correlated traits such as feed conversion ratio and growth rate showed some overlapping genes. Consistent with this result, distinct clusters of a coabundance network were enriched with microbial genes identified to be related with feed conversion ratio and growth rate or daily feed intake and residual feed intake. Microbial genes encoding for proteins related to cell wall biosynthesis, hemicellulose, and cellulose degradation and host-microbiome crosstalk (e.g., aguA, ptb, K01188, and murD) were associated with feed conversion ratio and/or average daily gain. Genes related to vitamin B12 biosynthesis, environmental information processing, and bacterial mobility (e.g., cobD, tolC, and fliN) were associated with residual feed intake and/or daily feed intake. This research highlights the association of the microbiome with feed conversion processes, influencing growth rate and appetite, and it emphasizes the opportunity to use relative abundances of microbial genes in the prediction of these performance traits, with potential implementation in animal breeding programs and dietary interventions.

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