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Jordan, D.

Publications and source records attributed to Jordan, D..

At least 37 records · Page 2Linked to original sources

Seminal root angle is associated with root system architecture in durum wheat

Optimal root system architecture (RSA) is critical for efficient resource capture in soils, hence being an interest in crop breeding. Seminal root angle (SRA) at the seedling stage in durum wheat has been suggested to be a good indicator of RSA. However, research on correlating such lab-based seedling root phenotyping to RSA at later phases of plant growth is limited, resulting in the importance of root trait variation seen in seedlings often being overstated. To explore the role of SRA in modifying RSA at later phases of plant growth, we assessed 11 genotypes contrasting in SRA (wide and narrow), grown in a rhizobox designed for phenotyping root systems of plants during late-tillering. Above-ground traits and root dry mass in different soil depths and across the entire soil volume were measured manually, while root architectural traits were extracted using image analysis and summarised by multiple factor analysis to describe RSA. When comparing the wide and narrow genotypes, no differences were detected for above-ground traits and total root dry mass. However, differences were observed in the allocation of root dry mass at different depths. The wide and narrow genotypes showed distinct RSAs, particularly in the upper soil (0 - 30 cm). The wide genotypes exhibited a spread-out root system with dense and thin roots, whereas the narrow genotypes had a compact root system with fewer but thicker roots. Our study demonstrated a clear difference in RSA between the wide and narrow genotypes, highlighting the association between SRA on the direction and distribution of root growth in plants at later growth stages.

plant biology↗

Newly Sequenced Genomes Reveal Patterns of Gene Family Expansion in select Dragonflies (Odonata: Anisoptera)

Gene family evolution plays a key role in shaping patterns of biodiversity across the tree of life. In Insecta, adaptive gene family turnover has broadly been tied to vision, diet, pesticide resistance, immune response and survival in extreme environments. Patterns of gene family evolution are of particular interest in Odonata (dragonflies and damselflies), which represents the first lineage to fly, and one of the most exceptional groups of predators. Previous work in Odonata found expansions of opsin genes are correlated with the diversification of the herbivorous insects that Odonata prey upon, but general trends in gene family turnover has not been studied in this order. Here, we show that two families of suborder Anisoptera (dragonflies), Libellulidae and Petaluridae, have expanded gene repertoire related to their unique life history and diversification patterns. These results are an important step towards understanding why Libellulidae is, generally, a species rich family of short lived species that are highly tolerant to poor water quality, while Petaluridae is a species poor family of habitat and behavioral specialists. Specifically, Libellulidae share expanded gene families related to immune response, desiccation response, and processing of free radicals, which all potentially enable many Libellulidae to inhabit low quality water bodies. Likewise, Petaluridae show unique patterns of gene turnover in gene families implicated in sensory perception, which could be tied to the unique semi-terrestrial lifestyle of the nymphs of this family. Furthermore, Odonata as a whole has a gene gene turnover rate that is an order of magnitude smaller than other studied insect orders, potentially contributing to the relatively low species diversity in the order Odonata compared to other insects. These results offer important hypotheses for the consideration of evolutionary drivers across Insecta.

evolutionary biology↗

General anaesthesia reduces the uniqueness of brain connectivity across individuals and across species

The human brain is characterised by idiosyncratic patterns of spontaneous thought, rendering each brain uniquely identifiable from its neural activity. However, deep general anaesthesia suppresses subjective experience. Does it also suppress what makes each brain unique? Here we used functional MRI under the effects of the general anaesthetics sevoflurane and propofol to determine whether anaesthetic-induced unconsciousness diminishes the uniqueness of the human brain: both with respect to the brains of other individuals, and the brains of another species. We report that under anaesthesia individual brains become less self-similar and less distinguishable from each other. Loss of distinctiveness is highly organised: it co-localises with the archetypal sensory-association axis, correlating with genetic and morphometric markers of phylogenetic differences between humans and other primates. This effect is more evident at greater anaesthetic depths, reproducible across sevoflurane and propofol, and reversed upon recovery. Providing convergent evidence, we show that under anaesthesia the functional connectivity of the human brain becomes more similar to the macaque brain. Finally, anaesthesia diminishes the match between spontaneous brain activity and meta-analytic brain patterns aggregated from the NeuroSynth engine. Collectively, the present results reveal that anaesthetised human brains are not only less distinguishable from each other, but also less distinguishable from the brains of other primates, with specifically human-expanded regions being the most affected by anaesthesia.

neuroscience↗

A Markovian dynamics for C. elegans behavior across scales

How do we capture the breadth of behavior in animal movement, from rapid body twitches to aging? Using high-resolution videos of the nematode worm C. elegans, we show that a single dynamics connects posture-scale fluctuations with trajectory diffusion, and longer-lived behavioral states. We take short posture sequences as an instantaneous behavioral measure, fixing the sequence length for maximal prediction. Within the space of posture sequences we construct a fine-scale, maximum entropy partition so that transitions among microstates define a high-fidelity Markov model, which we also use as a means of principled coarse-graining. We translate these dynamics into movement using resistive force theory, capturing the statistical properties of foraging trajectories. Predictive across scales, we leverage the longest-lived eigenvectors of the inferred Markov chain to perform a top-down subdivision of the worms foraging behavior, revealing both "runs-and-pirouettes" as well as previously uncharacterized finer-scale behaviors. We use our model to investigate the relevance of these fine-scale behaviors for foraging success, recovering a trade-off between local and global search strategies. SIGNIFICANCE STATEMENTComplex phenotypes, such as an animals behavior, generally depend on an overwhelming number of processes that span a vast range of scales. While there is no reason that behavioral dynamics permit simple models, by subsuming inherent nonlinearities and memory into maximally-predictive microstates, we find one for C. elegans foraging. The resulting "Markov worm" is effectively indistinguishable from real worm motion across a range of timescales, and we can decompose our model dynamics both to recover and discover behavioral states. Employing a simple form of substrate interactions, we connect postures to trajectories, illuminating how worms explore the environment. In more complex organisms, our approach can also link behaviors across time, from rapid muscular control to neuromodulation.

animal behavior and cognition↗

Escherichia coli isolated from commercial layer hens in Australia remain susceptible to critically important antimicrobials

Controlling the use of the most critically important antimicrobials (CIAs) in food animals has been identified as one of the key measures required to curb the transmission of antimicrobial resistant bacteria from animals to humans. Expanding the evidence demonstrating the effectiveness of restricting CIA usage for preventing the emergence of resistance to key drugs amongst commensal organisms in animal production would do much to strengthen international efforts to control antimicrobial resistance (AMR). As Australia has strict controls on antimicrobial use in layer hens, and internationally comparatively low levels of poultry disease due to strict national biosecurity measures, we investigated whether these circumstances have resulted in curtailing development of critical forms of AMR. The work comprised a cross-sectional national survey of 62 commercial layer farms with each assessed for AMR in Escherichia coli isolates recovered from faeces. Minimum inhibitory concentration analysis using a panel of 13 antimicrobials was performed on 296 isolates with those exhibiting phenotypic resistance to fluoroquinolones (a CIA) or multi-class resistance (MCR) subjected to whole genome sequencing. Overall, 52.0% of the isolates were susceptible to all antimicrobials tested, and all isolates were susceptible to ceftiofur, chloramphenicol and colistin. Resistance was observed to ampicillin (16.2%), cefoxitin (1.4%), ciprofloxacin (2.7%), florfenicol (2.4%), gentamicin (1.0%), streptomycin (4.7%), tetracycline (37.8%) and trimethoprim/sulfamethoxazole (10.5%). Multi-class resistance was observed in 23 isolates (7.7%), with one isolate (ST746) exhibiting resistance to five antimicrobial classes. Whole genome sequencing found that ciprofloxacin-resistant (fluoroquinolone) isolates were devoid of both known chromosomal mutations in the quinolone resistance determinant regions and plasmid-mediated quinolone resistance genes (qnr) - other than in one isolate (ST155) which carried the qnrS gene. Two MCR E. coli isolates with ciprofloxacin-resistance were found to be carrying known resistance genes including aadA1, dfrA1, strA, strB, sul1, sul2, tet(A), blaTEM-1B, qnrS1 and tet(A). Overall, this study found that E. coli from layer hens in Australia have low rates of AMR, likely due to strict control on antimicrobial usage achieved by the sum of regulation and voluntary measures.

microbiology↗

Anatomical drivers of stomatal conductance in sorghum lines with different leaf widths grown under different temperatures

O_LIImprovements in leaf water use efficiency (iWUE) can maintain crop productivity in water limited environments under rising temperatures. We investigated the leaf anatomical traits which underpin our recently identified link between leaf width (LW) and iWUE. C_LIO_LITen sorghum lines with varying LW were grown under three temperatures to expand the range of variation of both LW and gas exchange rates. Leaf gas exchange, surface morphology and cross-sectional anatomy were measured and analysed using structural equations modelling. C_LIO_LINarrower leaves had lower stomatal conductance (gs) and higher iWUE across growth temperatures. They also had smaller intercellular airspaces, stomatal size, percentage of open stomatal aperture relative to maximum, hydraulic pathway, mesophyll thickness, and leaf mass per area. Structural modelling revealed a developmental association among leaf anatomical traits that underpinned gs variation in sorghum. C_LIO_LIGrowing temperature and LW both impacted leaf gas exchange rates, but only LW directly impacted leaf anatomy. Wider leaves may be more productive under well-watered conditions, but consume more water for growth and development, which is detrimental under water stress. C_LI HighlightCoordination between leaf width and leaf anatomy underpins stomatal conductance variation in sorghum grown under different temperatures.

plant biology↗

Antimicrobial Resistance, Genomic, and Public Health Insights into Enterococcus spp. from Australian Cattle

Enterococci are opportunistic, potentially life-threatening pathogens of humans that are difficult to manage due to antimicrobial resistance. Historically, enterococci entering the food-chain through livestock have been viewed as a likely source of antimicrobial resistance in humans. Australian human-derived clinical enterococci have a propensity to be resistant to multiple classes of antimicrobials including vancomycin. Recent Australian studies involving pigs and chicken have virtually excluded these species as reservoirs of infection for resistant enterococci in humans. However, the Australian bovine population has not been similarly assessed. This study investigates the antimicrobial resistance profiles of enterococci from Australian cattle and the phylogenetic relationship between E. faecium isolated from cattle and human sepsis cases. Minimum inhibitory concentration assays were performed for E. faecium (n=343), E. faecalis (n=92), and E. hirae (n=284) against a panel of 15 antimicrobials. The majority of isolates were sensitive to all tested antimicrobials. Erythromycin resistance was most prevalent for E. faecium isolates (18.7%), daptomycin for E. faecalis (12.1%) and tetracycline for E. hirae (13.3%). Phenotypically, 1 E. faecalis was resistant to vancomycin and 9 were resistant to linezolid (E. faecium n=4, E. faecalis n=2, E. hirae n=3) but this was not confirmed with any know genotype. A subset of 67 E. faecium isolates selected for comparative phylogenetic analysis revealed that bovine isolates clustered with other livestock-derived and van-negative human isolates. In conclusion, there is a low prevalence of antimicrobial resistance amongst enterococci from Australian cattle which are unlikely to be precursor strains to vancomycin-resistant strains currently circulating in Australian hospitals. ImportanceEnterococci resistant to critically important antimicrobials such as vancomycin and linezolid are difficult to manage in health care settings. Historically, there has been the belief that livestock can act as a reservoir of resistance for human infections. Previous studies in poultry and pork have demonstrated that isolates derived from these livestock are unlikely to be precursor strains for currently circulating vancomycin resistant-Enterococci causing infection in humans. To date, there has been no study looking at the genetic similarity of bovine derived Enterococci and the relationship to human pathogenic strains. In this study we performed phenotypic and genotypic characterization of bovine derived Enterococci along with comparative phylogenetic analysis with other livestock derived and human sepsis derived E. faecium isolates. We found that while non-vancomycin resistant strain sharing occurs between hosts, cattle are unlikely to be precursor strains for vancomycin resistant human E. faecium infections.

microbiology↗

Loss of the E3 ubiquitin ligases UBR-5 or HECD-1 restores Caenorhabditis elegans development in the absence of SWI/SNF function

SWItch/Sucrose Non-Fermenting (SWI/SNF) complexes are a family of chromatin remodellers that are conserved across eukaryotes. Mutations in subunits of SWI/SNF cause a multitude of different developmental disorders in humans, most of which have no current treatment options. Here we identify an alanine to valine causing mutation in the SWI/SNF subunit snfc-5 (SMARCB1 in humans) that prevents embryonic lethality in C. elegans nematodes harbouring a loss-of-function mutation in the SWI/SNF subunit swsn-1 (SMARCC1/2 in humans). Furthermore, we found that the combination of this specific mutation in snfc-5 and a loss-of-function mutation in either of the E3 ubiquitin ligases ubr-5 (UBR5 in humans) or hecd-1 (HECTD1 in humans) can restore development to adulthood in swsn-1 loss-of-function mutants that otherwise die as embryos. Using these mutant models, we established a set of 335 genes that are dysregulated in SWI/SNF mutants that arrest their development embryonically but exhibit near wild-type levels of expression in the presence of suppressor mutations that prevent embryonic lethality, suggesting that SWI/SNF promotes development by regulating this specific subset of genes. In addition, we show that SWI/SNF protein levels are reduced in swsn-1; snfc-5 double mutants and partly restored to wild-type levels in swsn-1; snfc-5; ubr-5 triple mutants, consistent with a model in which UBR-5 regulates SWI/SNF levels by tagging the complex for proteasomal degradation. Our findings establish a link between two E3 ubiquitin ligases and SWI/SNF function and suggest that UBR5 and HECTD1 might be viable therapeutic targets for the many developmental disorders caused by missense mutations in SWI/SNF subunits.

developmental biology↗

Machine Learning Informs RNA-Binding Chemical Space

Small molecule targeting of RNA has emerged as a new frontier in medicinal chemistry, but compared to the protein targeting literature our understanding of chemical matter that binds to RNA is limited. In this study, we report Repository Of BInders to Nucleic acids (ROBIN), a new library of nucleic acid binders identified by small molecule microarray (SMM) screening. The complete results of 36 individual nucleic acid SMM screens against a library of 24,572 small molecules are reported (including a total of 1,627,072 interactions assayed). A set of 2,003 RNA-binding small molecules is identified, representing the largest fully public, experimentally derived library of its kind to date. Machine learning is used to develop highly predictive and interpretable models to characterize RNA-binding molecules. This work demonstrates that machine learning algorithms applied to experimentally derived sets of RNA binders are a powerful method to inform RNA-targeted chemical space.

biochemistry↗

Mapping Pharmacologically-induced Functional Reorganisation onto the Brain's Neurotransmitter Landscape

To understand how pharmacological interventions can exert their powerful effects on brain function, we need to understand how they engage the brains rich neurotransmitter landscape. Here, we bridge microscale molecular chemoarchitecture and pharmacologically-induced macroscale functional reorganisation, by relating the regional distribution of 19 neurotransmitter receptors and transporters obtained from Positron Emission Tomography, and the regional changes in functional MRI connectivity induced by 10 different mind-altering drugs: propofol, sevoflurane, ketamine, LSD, psilocybin, DMT, ayahuasca, MDMA, modafinil, and methylphenidate. Our results reveal that psychoactive drugs exert their effects on brain function by engaging multiple neurotransmitter systems. The effects of both anaesthetics and psychedelics on brain function are organised along hierarchical gradients of brain structure and function. Finally, we show that regional co-susceptibility to pharmacological interventions recapitulates co-susceptibility to disorder-induced structural alterations. Collectively, these results highlight rich statistical patterns relating molecular chemoarchitecture and drug-induced reorganisation of the brains functional architecture.

neuroscience↗

Genetic diversity analysis and characterization of Ugandan sorghum

The National Genebank of Uganda houses diverse and rich Sorghum bicolor germplasm collection. This genetic diversity resource is untapped, under-utilized and has not been systematically incorporated into sorghum breeding programs. In this study, we characterized the germplasm collection using whole genome SNP markers. Discriminant analysis of principal components (DAPC) was implemented to study racial ancestry of the accessions in comparison to a global sorghum diversity set and characterize sub-groups and admixture in the Ugandan germplasm. Genetic structure and phylogenetic analysis was conducted to identify distinct genotypes in the Ugandan collection and relationships among groups. Furthermore, in a case study for identification of potentially useful adaptive trait variation for breeding, we performed genome-wide association studies for juvenile cold tolerance. Genomic regions potentially involved in adaptation of Ugandan sorghum varieties to cooler climatic conditions were identified that could be of interest for expansion of sorghum production into temperate latitudes. The study demonstrates how genebank genomics can potentially facilitate effective and efficient usage of valuable, untapped germplasm collections for agronomic trait evaluation and subsequent allele mining.

plant biology↗

Proximity to human settlement is directly related to carriage of critically important antimicrobial-resistant Escherichia coli and Klebsiella pneumoniae in Silver Gulls

Human population and activities play an important role in dissemination of antimicrobial resistant bacteria. This study investigated the relationship between carriage rates of critically important antimicrobial-resistant (CIA-R) Escherichia coli and Klebsiella pneumoniae by Silver Gulls and their proximity to human populations. Faecal swabs (n=229) were collected from Silver Gulls across 10 southern coastline locations in Western Australia (WA). The sampling locations included main town centres and remote areas. Fluoroquinolone and extended-spectrum cephalosporin-resistant E. coli and K. pneumoniae were isolated and tested for antimicrobial sensitivity. Genome sequencing was performed to validate phenotypic resistance profiles and determine the molecular characteristics of strains. CIA-R E. coli and K. pneumoniae were detected in 69 (30.1%) and 20 (8.73%) of the faecal swabs respectively. Two large urban locations tested positive for CIA-R E. coli (frequency ranging from 34.3%-84.3%), and/or for CIA-R K. pneumoniae (frequency ranging from 12.5%-50.0%). A small number of CIA-R E. coli (3/31, 9.7%) were identified at a small tourist town, but no CIA-R bacteria were recovered from gulls at remote sites. Commonly detected E. coli sequence types (STs) included ST131 (12.5%) and ST1193 (10.0%), and five K. pneumoniae STs were found. Resistance genes including blaCTX-M-3, blaCTX-M-15 and blaCTX-M-27 were identified in both bacterial species. High-level colonisation of CIA-R E. coli and K. pneumoniae in Silver Gulls in and around urban areas compared to remote locations substantiates that anthropogenic activities are strongly associated with acquisition of resistant bacteria by gulls. ImportanceHumans play an important role in dissemination of antimicrobial resistant bacteria. This study investigated the relationship between carriage rates of resistant bacterial pathogens (Escherichia coli and Klebsiella pneumoniae) among Silver Gulls and their proximity to human populations. The frequency of resistant E. coli carriage was high (ranging from 34.3 - 84.3%) in the samples collected from areas with high human population density while resistant K. pneumoniae frequencies at these sites varied from 0 to 50%. However, resistant E. coli and K. pneumoniae were not recovered from any of the remote sites that did not have a permanent human population. This study, conducted across a large stretch of the southwestern Australian coastline, indicated that seagulls act as vectors in carrying and disseminating antimicrobial resistant bacteria, including clinically significant strains. High-level colonisation of resistant E. coli and K. pneumoniae in Silver Gulls in and around urban areas compared to remote locations substantiates that human activities are strongly associated with acquisition of resistant bacteria by Silver gulls.

microbiology↗

Validation of selective agars for detection and quantification of Escherichia coli resistant to critically important antimicrobials

Success in the global fight against antimicrobial resistance (AMR) is likely to improve if surveillance can be performed more rapidly, affordably and on a larger scale. An approach based on robotics and agars incorporated with antimicrobials has enormous potential to achieve this. However, there is a need to identify the combinations of selective agars and key antimicrobials yielding the most accurate counts of susceptible and resistant organisms. A series of designed experiments involving 1,202 plates identified the best candidate-combinations from six commercially available agars and five antimicrobials using 18 Escherichia coli strains as either pure cultures or inoculums within faeces. The effect of various design factors on colony counts were analysed in generalised linear models. Without antimicrobials, Brilliance E. coli (Brilliance) and CHROMagar ECC (CHROMagar) agars yielded 28.9% and 23.5% more colonies than MacConkey agar. The order of superiority of agars remained unchanged when faecal samples with and without spiking of resistant E. coli were inoculated onto agars with or without specific antimicrobials. When incorporating antimicrobials at varying concentrations, it was revealed that ampicillin, tetracycline and ciprofloxacin are suitable for incorporation into Brilliance and CHROMagar agars at all defined concentrations. Gentamicin was only suitable for incorporation at 8 and 16 g/mL while ceftiofur was only suitable at 1 g/mL. CHROMagar ESBL agar supported growth of a wider diversity of extended-spectrum cephalosporin-resistant E. coli. The findings demonstrate the potential for combining robotics with agars to deliver AMR surveillance on a vast scale with greater sensitivity of detection and strategic relevance. IMPORTANCEEstablished models of surveillance for AMR in livestock typically have a low sampling intensity which creates a tremendous barrier to understanding the variation of resistance amongst animal and food enterprises. However, developments in laboratory robotics now make it possible to rapidly and affordably process high volumes of samples. Combined with modern selective agars incorporating antimicrobials, this forms the basis of a novel surveillance process for identifying resistant bacteria by chromogenic reaction including accurately detecting and quantifying their presence even when present at low concentration. As Escherichia coli is a widely preferred indicator bacterium for AMR surveillance, this study identifies the optimal selective agar for quantifying resistant E. coli by assessing the growth performance on agars with antimicrobials. The findings are the first step towards exploiting laboratory robotics in an up-scaled approach to AMR surveillance in livestock with wider adaptations in food, clinical microbiology and public health.

microbiology↗

Maximally predictive ensemble dynamics from data

We leverage the interplay between microscopic variability and macroscopic order to connect physical descriptions across scales directly from data, without underlying equations. We reconstruct a state space by concatenating measurements in time, building a maximum entropy partition of the resulting sequences, and choosing the sequence length to maximize predictive information. Trading non-linear trajectories for linear, ensemble evolution, we analyze reconstructed dynamics through transfer operators. The evolution is parameterized by a transition time{tau} : capturing the source entropy rate at small{tau} and revealing timescale separation with collective, coherent states through the operator spectrum at larger{tau} . Applicable to both deterministic and stochastic systems, we illustrate our approach through the Langevin dynamics of a particle in a double-well potential and the Lorenz system. Applied to the behavior of the nematode worm C. elegans, we derive a "run-and-pirouette" navigation strategy directly from posture dynamics. We demonstrate how sequences simulated from the ensemble evolution capture both fine scale posture dynamics and large scale effective diffusion in the worms centroid trajectories and introduce a top-down, operator-based clustering which reveals subtle subdivisions of the "run" behavior. POPULAR SUMMARYComplex structure is often composed from a limited set of relatively simple building blocks; such as novels from letters or proteins from amino acids. In musical composition, e.g., sounds and silences combine to form longer time scale structures; motifs form passages which in turn form movements. The challenge we address is how to identify collective variables which distinguish structures across such disparate time scales. We introduce a principled framework for learning effective descriptions directly from observations. Just as a musical piece transitions from one movement to the next, the collective dynamics we infer consists of transitions between macroscopic states, like jumps between metastable states in an effective potential landscape. The statistics of these transitions are captured compactly by transfer operators. These operators play a central role, guiding the construction of maximally-predictive short-time states from incomplete measurements and identifying collective modes via eigenvalue decomposition. We demonstrate our analysis in both stochastic and deterministic systems, and with an application to the movement dynamics of an entire organism, unravelling new insight in long time scale behavioral states directly from measurements of posture dynamics. We can, in principle, also make connections to both longer or shorter timescales. Microscopically, postural dynamics result from the fine scale interactions of actin and myosin in the muscles, and from electrical impulses in the brain and nervous system. Macroscopically, behavioral dynamics may be extended to longer time scales, to moods or dispositions, including changes during aging, or over generations due to ecological or evolutionary adaptation. The generality of our approach provides opportunity for insights on long term dynamics within a wide variety of complex systems.

biophysics↗

Robotic Antimicrobial Susceptibility Platform (RASP): A Next Generation Approach to One-Health Surveillance of Antimicrobial Resistance.

BackgroundSurveillance of antimicrobial resistance (AMR) is critical to reducing its wide-reaching impact. Its reliance on sample size invites solutions to longstanding constraints regarding scalability. A robotic platform (RASP) was developed for high-throughput AMR surveillance in accordance with internationally recognised standards (CLSI and ISO 20776-1:2019) and validated through a series of experiments. MethodsExperiment A compared RASPs ability to achieve consistent MICs to that of a human technician across eight replicates for four E. coli isolates. Experiment B assessed RASPs agreement with human performed MICs across 91 E. coli isolates with a diverse range of AMR profiles. Additionally, to demonstrate its real-world applicability, the RASP workflow was then applied to five faecal samples where a minimum of 47 E. coli per animal (239 total) were evaluated using an AMR indexing framework. ResultsFor each drug-rater-isolate combination in experiment A, there was a clear consensus of the MIC and deviation from the consensus remained within one doubling-dilution (the exception being gentamicin at two dilutions). Experiment B revealed a concordance correlation coefficient of 0.9670 (95%CI: 0.9670 - 0.9670) between the robot and human performed MICs. RASPs application to the five faecal samples highlighted the intra-animal diversity of gut commensal E. coli, identifying between five and nine unique isolate AMR phenotypes per sample. ConclusionsWhile adhering to internationally accepted guidelines, RASP was superior in throughput, cost and data resolution when compared to an experienced human technician. Integration of robotics platforms in the microbiology laboratory is a necessary advancement for future One-Health AMR endeavours.

microbiology↗

The Orsay Virus as a model for population-wide viral infection dynamics

To this day, epidemics pose a considerable threat to mankind. Experimental models that simulate the spread of infectious diseases are thus crucial to the inception of effective control policies. Current models have had great success incorporating virulence and host immune response but do rarely take host genetics, behavior and host environment into account. Here, we present a full-scale imaging setup that utilizes the infection of the nematode C. elegans with a positive-stranded RNA virus (Orsay Virus) to probe key epidemiological parameters and simulate the spread of infection in a whole population. We demonstrate that our system is able to quantify infection levels and host behavior at a high sampling rate and show that different host genetic backgrounds can influence viral spread, while also highlighting the influence of infection on various host behaviors. Future work will allow the isolation of key behavioral and environmental factors that affect viral spread, potentially enabling novel policies to combat the spread of viral infections. Significance StatementIn the ongoing COVID-19 pandemic, we struggle to find effective control policies that "stop the spread". While current animal models of virus spread in populations are highly sophisticated, they rarely explore effects of host behavior and its environment. We developed an experimental animal model system that allows us to visualize virus transmission in whole populations of C. elegans while also measuring behaviors. We were able to demonstrate how C. elegans genetics influences the progression of viral infection in a population and how animals adjust their behavior when infected. In the future, we envision that animal model systems like ours are used to test the effects of viral control policies on viral spread before they are applied in real world scenarios.

immunology↗

Criticality Creates a Functional Platform for Network Transitions between Internal and External Processing Modes in the Human Brain

Continuous switching between internal and external modes in the brain is a key process of constructing inner models of the outside world. However, how the brain continuously switches between two modes remains elusive. Here, we propose that a large synchronization fluctuation of the brain network emerging only near criticality (i.e., a balanced state between order and disorder) spontaneously creates temporal windows with distinct preferences for integrating internal information of the network and external stimuli. Using a computational model and empirical data analysis during alterations of consciousness in human, we present that synchronized and incoherent networks respectively bias toward internal and external information with specific network configurations. The network preferences are the most prominent in conscious states; however, they disrupt in altered states of consciousness. We suggest that criticality produces a functional platform of the brains capability for continuous switching between two modes, which is crucial for the emergence of consciousness.

neuroscience↗

Translational adaptation to heat stress is mediated by 5-methylcytosine RNA modification in Caenorhabditis elegans

Methylation of carbon-5 of cytosines (m5C) is a post-transcriptional nucleotide modification of RNA found in all kingdoms of life. While individual m5C-methyltransferases have been studied, the impact of the global cytosine-5 methylome on development, homeostasis and stress remains unknown. Here, using Caenorhabditis elegans, we generated the first organism devoid of m5C in RNA, demonstrating that this modification is non-essential. We determined the localisation and enzymatic specificity of m5C sites in RNA in vivo and showed that animals devoid of m5C are sensitive to temperature stress. At the molecular level, we showed that loss of m5C specifically impacts decoding of leucine and proline thus reducing the translation efficiency of transcripts enriched in these amino acids. Finally, we found translation of leucine UUG codons to be the most strongly affected upon heat shock, suggesting a role of m5C tRNA wobble methylation in the adaptation to heat stress.

genetics↗