Biology subjects

Smith, M. R.

Publications and source records attributed to Smith, M. R..

At least 19 recordsLinked to original sources

bioRxiv2026

Additive Effects Dominate Legume Responses to Combined Heat and Drought Stress: A Quantitative Review

Concurrent exposure to heat and drought stress compromises legume productivity, yet their combined effects are rarely quantified systematically. We compiled a database of 18 studies covering seven legume species. From these, we extracted 929 physiological, biochemical, and yield-related traits and calculated actual-to-additive ratios to classify heat-drought interactions as antagonistic (ratio < 1), additive (ratio = 1), or synergistic (ratio > 1). Additive heat-drought relationships accounted for 59 % of all classifiable observations, 37% relationships were antagonistic, and 4% synergistic. The relationship varied with species, genotype, trait, and experimental conditions highlighting the complexity of combined abiotic stress effects. The results challenge the common assumption that concurrent stresses invariably exacerbate damage and underscore the need for more realistic, quantitatively defined stress treatments as well as frameworks that integrate trait-level responses into predictive models of crop growth and development. Our synthesis provides a quantitative foundation to understand legume phenotypes under the increasingly frequent co-occurrence of heat and drought stress and identifies research areas where further work is needed to improve insight into combined stress responses. HighlightsO_LICombined heat and drought responses were mainly additive or antagonistic. C_LIO_LIEvidence is biased toward few legumes and controlled environments. C_LIO_LIField-based, multi-species studies are needed to identify adaptive traits. C_LI

plant biology↗

bioRxiv2026

Development of a metabolomics-based index to monitor dietary effects on chronic inflammation: The Dietary Metabolomics Inflammation Index

BackgroundThe Dietary Inflammatory Index (DII) is widely used to assess the inflammatory potential of diet, but it relies on self-reported dietary assessment and does not directly capture individual differences in metabolism as an intermediate connection to inflammation. High-resolution metabolomics provides objective measurements that complement dietary assessment to support precision nutrition to control inflammation. ObjectiveWe developed, tested, and applied a Dietary Metabolite Inflammatory Index (DMII) to assess diet-related chronic inflammation using metabolites measured by liquid chromatography-high-resolution mass spectrometry. MethodsDII was calculated using dietaryindex R package with Block Food Frequency Questionnaire (FFQ) data. To develop the DMII, chronic inflammation-related dietary metabolites corresponding to the DII food parameters were found through a literature review. Dietary metabolites were identified and quantified by authentic standards by our established laboratory procedures. DMII uses the same inflammatory effect scores as the DII. Three DMII versions were developed: concentration-based, median-based, and quintile-based DMII. Mean and standard deviation of 29 dietary metabolites were calculated by using 3025 human plasma samples from 3 studies. DMII was tested in the Center for Health Discovery and Well-Being cohort (CHDWB) and the Atlanta African American Maternal and Child cohort (ATLAA) using chronic inflammation biomarkers, including high-sensitivity C-reactive protein (hs-CRP), CRP, and IL-6. The median-based DMII was further applied to four Alzheimers disease metabolomics datasets as a proof-of-concept application. ResultsIn the CHDWB study, concentration-based DMII had a weak positive correlation with Block FFQ-derived DII and strongly correlated with median-based and quintile-based DMII. In the same study, all three DMII versions had significant positive correlations with hs-CRP and IL-6. In the ATLAA study, only concentration-based DMII was positively associated with CRP and IL-6. Higher median-based DMII was associated with higher odds of Alzheimers disease. ConclusionsDMII provides a metabolomics-based framework for assessing diet-related chronic inflammation using metabolomics data. This metabolomics approach may complement self-reported dietary assessment to use diet and nutrition to help protect against chronic disease linked to inflammation.

biochemistry↗

bioRxiv2026

Trait stability of diverse kabuli chickpea germplasm from delayed sowing in a rainfed environment

Structured AbstractO_ST_ABSContext and ObjectiveC_ST_ABSDelayed sowing can expose chickpea crops to stress during the critical period for yield determination, but the effect of yield components and phenology to grain yield variation is not well characterised in diverse germplasm under rainfed conditions. Identifying genetic resources for grain yield improvement requires integration of multi-environment trial and genomic analyses to disentangle direct yield effects from indirect effects of phenology. This study aimed to (1) characterise genotype by environment interaction patterns for grain yield, yield components and phenology across times of sowing and seasons, and (2) identify genomic regions associated with improved grain yield that are present in genebank accessions but absent from current Australian commercial cultivars. MethodsA diversity panel of 141 kabuli chickpea genotypes, including six commercial Australian cultivars and 135 genebank accessions, was evaluated across six rainfed trials at Narrabri, New South Wales over three seasons (2018 to 2020) under typical (MAIN) and delayed (LATE) sowing. Multi-environment trial analyses with factor analytic models partitioned genotype by environment interactions for grain yield, 100-seed weight, seed number, and thermal time to flowering, podding, and maturity. Haplotype block analysis identified high variance blocks associated with seed number, classified by their overlap with high variance thermal time to flowering blocks, to distinguish from effects mediated by phenology. Results and ConclusionsDelayed sowing reduced grain yield by up to 1.04 t ha-{superscript 1}, driven primarily by reductions in seed number rather than 100-seed weight. Accelerated phenology was a key component of adaptation among commercial cultivars. Four haploblocks with high block variance for seed number were identified across all six trials. SignificanceSeed number was the dominant driver of grain yield variation in this diverse kabuli chickpea panel. Targeted introgression of rare superior haplotypes from genebank accessions provides an opportunity to broaden the genetic base of Australian kabuli chickpea and improve yield through higher seed number, with relevance to chickpea production systems facing similar climate variability. HighlightsDelayed sowing reduced grain yield in diverse kabuli chickpea germplasm by up to 1.04 t ha-1 across three years and six trials in northern New South Wales. Seed number, not seed weight, was the dominant driver of grain yield variation, and a shorter phenological duration was associated with higher seed number. Across all six trials, haplotype block analysis identified four genomic regions in high linkage disequilibrium with high variance for seed number and low variance for flowering time. The accession FLIP 94 62C uniquely carried rare superior haplotypes at two chromosome 4 blocks, the haplotype at the 17.0 Mb block was the most superior haplotype in all trials while the haplotype at the 8.5Mb block was most superior only in the most heat stressed environment.

plant biology↗

bioRxiv2026

Pyridoxine supplementation confers protection against SGPL1R222Q variant sphingosine phosphate lyase insufficiency syndrome

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare condition causing nephrotic syndrome, neuropathy, and other manifestations. SPLIS is caused by mutations in SGPL1, which encodes sphingosine-1-phosphate lyase (SPL), a pyridoxal 5-phosphate (PLP)-dependent enzyme needed to degrade the bioactive sphingolipid sphingosine-1-phosphate (S1P). Supplementation with the PLP precursor pyridoxine benefits some individuals with PLP-dependent enzymopathies. We sought to establish whether pyridoxine has therapeutic activity in SPLIS. Neurological improvement, plasma S1P normalization, and increased SPL activity in patient-derived fibroblasts were observed after pyridoxine supplementation in a patient with R222Q-variant SPLIS. Additionally, PLP dose-dependently augmented recombinant R222Q-variant SPL activity. To further explore pyridoxines effects, gene editing was employed to create an R222Q-variant SPLIS mouse model. SPLR222Q mice fed pyridoxine-enriched chow lacked obvious phenotypes. However, SPL inactivation, S1P accumulation, wasting, anemia, proteinuria, and glomerulosclerosis developed in SPLR222Q but not WT mice fed chow with reduced pyridoxine. Ultrastructural analysis and super-resolution microscopy showed podocyte loss and foot process effacement. Transcriptional profiling revealed a pattern of cytokine upregulation and extracellular matrix remodeling. Inhibiting S1P production prevented nephrosis in SPLR222Q mice fed chow lacking pyridoxine. Our findings establish a novel SPLIS mouse model that recapitulates R222Q-variant SPLIS, demonstrates its responsiveness to pyridoxine, and implicates S1P in its pathophysiology.

molecular biology↗

bioRxiv2025

Mitochondrial ROS-induced metabolic alterations differentially regulate ferroptosis sensitivity

Ferroptosis is an iron-catalyzed lipid peroxidation (LP)-dependent cell death. Induction of mitochondrial ROS (mtROS) is crucial in the execution of ferroptosis, but the underlying mechanism remains unclear. Through utilizing the hepatocyte model and RNA-seq analysis, we determined mtROS-dependent metabolic changes that modulate ferroptosis sensitivity. Elevated mtROS production and LP suppressed glycolysis, fatty acid oxidation, and citric acid cycle activity, representing adaptive responses that protect cells from ferroptosis. On the other hand, mtROS-driven signaling impaired glutathione biosynthesis and downregulated genes involved in coenzyme Q10 (CoQ) biosynthesis, including those in the mevalonate pathway and CoQ8A, a key stabilizer of the CoQ biosynthetic complex. Importantly, silencing CoQ8A expression enhanced, whereas overexpression of CoQ8A reduced, ferroptosis susceptibility of hepatocytes and various cancer cell types. The mtROS-mediated downregulation of CoQ8A was dependent on farnesoid X receptor (FXR) and retinoid X receptors (RXRs). Collectively, our findings highlight that mtROS promotes ferroptosis, at least in part, by suppressing glutathione and CoQ biosynthesis.

cell biology↗

bioRxiv2025

The potential to breed for genetic legacy effects in sustainable farming systems

Legume crops provide protein-rich food, critical disease breaks in cereal rotations, and contribute to soil fertility through symbiotic nitrogen fixation. However, crop improvement programs typically focus on within-crop performance rather than system-level benefits. We hypothesise that legacy effects (the influence of one crops genotype on subsequent crop performance) are under genetic control and could be leveraged in breeding programs. To test this, we evaluated how 309 genetically diverse mungbean genotypes influence subsequent wheat performance. The mungbean panel was grown, followed by a single wheat cultivar sown in the same plot locations. Remarkably, wheat yield varied by nearly 1 t ha{square}{superscript 1} (2.52-3.49 t ha{square}{superscript 1}) depending solely on the preceding mungbean genotype, with legacy traits displaying moderate heritability (H{superscript 2}: 0.43-0.65), demonstrating untapped genetic potential for breeding. Analyses of mungbean traits, soil properties, and volatile organic compounds implicated root architecture, symbiotic nitrogen fixation and soil microbiome as potential biological drivers of legacy effects. Haplotype mapping identified genomic regions in mungbean associated with wheat yield and protein, revealing trade-offs between within-crop and legacy performance. Genetic simulations using empirically derived marker effects compared genomic selection strategies targeting mungbean yield, wheat yield, or both simultaneously. Balanced selection (50:50 weighting) achieved simultaneous gains in both crops (19.5% and 7.6%), highlighting the opportunity to breed for system-level productivity with reduced input requirements.

plant biology↗

bioRxiv2025

Metabolic Trajectories During Surgical Stress in Patients Undergoing Cardiac Surgery

Stress hyperglycemia (SH) during acute illness is linked to adverse surgical outcomes, yet the accompanying metabolic perturbations are incompletely characterized. We profiled longitudinal metabolic changes in adults without diabetes undergoing cardiac surgery to identify pathways associated with perioperative SH (defined as point-of-care glucose [≥]140 mg/dL on [≥]3 readings or [≥]180 mg/dL once). Blood was collected at baseline before surgery (T0) and at 2 h (T1), 24-48 h (T2), and 72-96 h (T3) after surgical initiation. High-resolution metabolomics (LC-MS) was integrated with continuous glucose monitoring and inflammatory/cardiac biomarkers. At T0, several pathways were associated with subsequent SH, including bile acid metabolism, the carnitine shuttle, and fatty-acid oxidation, suggesting preoperative metabolic susceptibility. In longitudinal analyses, participants who developed SH showed coordinated postoperative changes with significant enrichment of pathways not evident at baseline, C21-steroid hormone biosynthesis, glycerophospholipid metabolism, and glycosphingolipid (ceramide) metabolism, consistent with lipid remodeling and inflammatory signaling during surgical stress. Individuals with SH also exhibited higher inflammatory biomarker levels (high-sensitivity C-reactive protein and soluble urokinase plasminogen activator receptor). A machine-learning model using early metabolomic features predicted SH with an area under the receiver operating characteristic curve of 0.86. These findings highlight distinct preoperative and perioperative metabolic trajectories associated with SH and implicate established dysglycemia-related pathways, as well as stress-induced pathways in perioperative metabolic dysregulation. Pathway enrichment analyses were exploratory and hypothesis-generating; validation in larger cohorts and assessment of implications for clinical outcomes are warranted.

biochemistry↗

bioRxiv2025

Spatial probabilistic patterns of joint heat and water stress of chickpea in Australia

Quantitative characterisation of the crop environment for breeding and agronomic applications is commonly based on the cluster analysis of isolated climate factors, such as drought and temperature. The focus on individual climate factors fails to account for both the correlations between climate factors in space and time, and the contemporary models of dynamic biological systems where multiple interacting factors simultaneously shape the crop phenotype. With a focus on chickpea in Australia, our aims are to (1) assess the associations between climate factors and actual yield measured in 578 location -years; associations are investigated on a biologically relevant developmental scale; (2) establish the spatial, probabilistic patterns of multivariate environment types at regional and continental scales; and (3) evaluate the shifts in the frequency of environment types with climate change. We identified a syndrome of hot, dry and high vapour pressure deficit with three intensities of stress classified as low, medium and high. Measured yield, in the range from failed crop to 4 t ha-1, aligned more strongly with this multivariate syndrome than with isolated climate factors, with stronger associations at regional than continental scale. The frequency of stressful environment types increased with realised climate change and was most severe in the chickpea growing heartland of central Queensland; our models show that increased frequency of stress could be partially mitigated with earlier flowering varieties. Our findings will inform chickpea agronomy, phenotyping and breeding.

physiology↗

bioRxiv2025

Cellulase secretion by engineered Pseudomonas putida enables growth on cellulose oligomers.

Pseudomonas putida is an attractive synthetic biology platform organism for chemical synthesis from low-grade feedstocks due to its high tolerance to chemical solvents and lignin-derived small molecules that are often inhibitory to other biotechnologically relevant microorganisms. However, there are few molecular tools available for engineering P. putida and other gram-negative bacteria to secrete non-native enzymes for extracellular feedstock depolymerisation. In this study P. putida was transformed to secrete cellulase enzymes and evaluated for growth on polymeric or oligomeric cellulose substrates. Active exo- and endocellulase enzymes were secreted into the culture supernatant, and a preferred set of twin-arginine translocase secretion signal peptides were identified. Extracellular cellulase activity was sufficient to support growth of P. putida using cellotriose or cellotetraose as the sole source of carbon and energy. This work supports progress towards consolidated bioprocessing of cellulosic materials using P. putida, and advances the state of engineered protein secretion in gram negative bacteria. Key PointsO_LIEngineered Pseudomonas putida secreted cellulase enzymes into the culture medium C_LIO_LICellulase activity was sufficient to support growth on cellulose oligomers C_LI

synthetic biology↗

bioRxiv2024

Multi-Tissue Metabolomics Reveal mtDNA- and Diet-Specific Metabolite Profiles in a Mouse Model of Cardiometabolic Disease

RationaleExcess consumption of sugar- and fat-rich foods has heightened the prevalence of cardiometabolic disease, which remains a driver of cardiovascular disease- and type II diabetes-related mortality globally. Skeletal muscle insulin resistance is an early feature of cardiometabolic disease and is a precursor to diabetes. Insulin resistance risk varies with self-reported race, whereby, African-Americans have a greater risk of diabetes development relative to their White counterparts. Self-reported race is strongly associated with mitochondrial DNA (mtDNA) haplogroups, and previous reports have noted marked differences in bioenergetic and metabolic parameters in cells belonging to distinct mtDNA haplogroups, but the mechanism of these associations remains unknown. Additionally, distinguishing nuclear DNA (nDNA) and mtDNA contributions to cardiometabolic disease remains challenging in humans. The Mitochondrial-Nuclear eXchange (MNX) mouse model enables in vivo preclinical investigation of the role of mtDNA in cardiometabolic disease development, and has been implemented in studies of insulin resistance, fatty liver disease, and obesity in previous reports. MethodsSix-week-old male C57nDNA:C57mtDNA and C3HnDNA:C3HmtDNA wild-type mice, and C57nDNA:C3HmtDNA and C3HnDNA:C57mtDNA MNX mice, were fed sucrose-matched high-fat (45% kcal fat) or control diet (10% kcal fat) until 12 weeks of age (n = 5/group). Mice were weighed weekly and total body fat was collected at euthanasia. Gastrocnemius skeletal muscle and plasma metabolomes were characterized using untargeted dual-chromatography mass spectrometry; both hydrophilic interaction liquid chromatography (HILIC) and C18 columns were used, in positive- and negative-ion modes, respectively. ResultsComparative analyses between nDNA-matched wild-type and MNX strains demonstrated significantly increased body fat percentage in mice possessing C57mtDNA regardless of nDNA background. High-fat diet in mice possessing C57mtDNA was associated with differential abundance of phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamines, and glucose. Conversely, high-fat diet in mice possessing C3HmtDNA was associated with differential abundance of phosphatidylcholines, cardiolipins, and alanine. Glycerophospholipid metabolism and beta-alanine signaling pathways were enriched in skeletal muscle and plasma, indicating mtDNA-directed priming of mitochondria towards oxidative stress and increased fatty acid oxidation in C57nDNA:C57mtDNA wild-type and C3HnDNA:C57mtDNA MNX mice, relative to their nDNA-matched counterparts. In mtDNA-matched mice, C57mtDNA was associated with metabolite co-expression related to the pentose phosphate pathway and sugar-related metabolism; C3HmtDNA was associated with branched chain amino acid metabolite co-expression. ConclusionsThese results reveal novel nDNA-mtDNA interactions that drive significant changes in metabolite levels. Alterations to key metabolites involved in mitochondrial bioenergetic dysfunction and electron transport chain activity are implicated in elevated beta-oxidation during high-fat diet feeding; abnormally elevated rates of beta-oxidation may be a key driver of insulin resistance. The results reported here support the hypothesis that mtDNA influences cardiometabolic disease-susceptibility by modulating mitochondrial function and metabolic pathways.

molecular biology↗

bioRxiv2022

Functionally competent CD4+ T cells express high levels of T-bet in Plasmodium chabaudi infected young mice

The immune system plays an important role in the elimination of Plasmodium parasites that cause malaria, which affect children the most worldwide. Immunity to malaria, especially in young children is poorly understood due to the absence of a developmentally-equivalent rodent model to study the pathogenesis of disease. We have developed a mouse model using 15-day old mice (pups) of malaria infection in neonatal mice. Using C57BL/6 pups, we determined that P. chabaudi infection decreases the growth rate of young mice compared to controls, and results in 60% mortality, and neurological damage not present in adults, as indicated by a battery of behavioral assays. When all splenic cells were stimulated in vitro stimulation, cells from pups proliferated faster than adult cells, but purified CD4 T cells were slower. Upon infection with Plasmodium parasites, both adult and pup CD4+ T cells were activated and differentiated to an effector T cell (Teff) phenotype; however, pup CD4+ Teff were less differentiated than adult Teff. Pup CD4+ T cells also produced more IL-2 than cells from adult B6 mice, and TNF- was increased in parasite-specific BALB/c pup T cells. Interestingly, there were more pup CD4+T-bethi Teff after infection suggestive of increased Th1 commitment, potentially contributing to cerebral symptoms.

immunology↗

bioRxiv2021

TreeSearch: morphological phylogenetic analysis in R

TreeSearch is an R package for phylogenetic analysis, optimized for morphological datasets. Tree search may be conducted using equal or implied step weights with an explicit (albeit inexact) allowance for inapplicable character entries, avoiding some of the pitfalls inherent in standard parsimony methods. Profile parsimony and user-specified optimality criteria are supported. A graphical interface, which requires no familiarity with R, is designed to help a user to improve the quality of datasets through critical review of underpinning character codings; and to obtain additional information from results by identifying and summarizing clusters of similar trees, mapping the distribution of trees, and removing rogue taxa that obscure underlying relationships. Taken together, the package aims to support methodological rigour at each step of data collection, analysis, and the exploration of phylogenetic results.

evolutionary biology↗

bioRxiv2021

Physiological and genetic drivers underpinning canopy development are associated with durum wheat yield in rainfed environments

New durum wheat (Triticum turgidum L. ssp. Durum) cultivars with improved adaptation to variable rainfall environments are required to sustain productivity in the face of climate change. Physiological traits related to canopy development underpin the production of biomass and yield, as they interact with solar radiation and affect the timing of water use throughout the growing season. This study explored the temporal canopy dynamics of durum wheat using a nested-association mapping population evaluated for longitudinal normalized difference vegetation index (NDVI) measurements. Association mapping was performed to identify quantitative trait loci (QTL) for time-point NDVI and spline-smoothed NDVI trajectory traits. Yield effects associated with QTL for canopy development were investigated using data from four rainfed field trials. Four QTL associated with slower canopy closure, improved yield in specific environments, and notably, were not associated with a yield penalty in any environment. This was likely due to optimised timing of water-use and pleiotropic effects on yield component traits, including spike number and spike length. Overall, this study suggests that slower canopy closure is beneficial for durum wheat production in rainfed environments. Selection for traits or loci associated with canopy development may improve yield stability of durum wheat in water limited environments.

genetics↗

bioRxiv2020

Metabolic effects of the schizophrenia-associated 3q29 deletion are sex-specific and uncoupled from behavioral phenotypes

The 1.6 Mb 3q29 deletion is associated with developmental and psychiatric phenotypes. Reduced birthweight and a high prevalence of feeding disorders in patients suggest underlying metabolic dysregulation. We investigated 3q29 deletion-induced metabolic changes using the B6.Del16+/Bdh1-Tfrc mouse model. We found that B6.Del16+/Bdh1-Tfrc animals preferentially use dietary lipids as an energy source. Untargeted metabolomics showed a strong sex-dependent effect of the 3q29 deletion on fat metabolism. A high-fat diet (HFD) partially rescued the 3q29 deletion-associated weight deficit in females, but not males. Untargeted metabolomics after HFD revealed persistent fat metabolism alterations in females. The HFD did not affect B6.Del16+/Bdh1-Tfrc behavioral phenotypes, suggesting that 3q29 deletion-associated metabolic and behavioral outcomes are uncoupled. Our data indicate a HFD intervention in 3q29 deletion syndrome may improve weight phenotypes without exacerbating behavioral manifestations. Our study also highlights the importance of assessing sex in metabolic studies and suggests mechanisms underlying 3q29 deletion-associated metabolic phenotypes are sex-specific.

genetics↗

bioRxiv2020

Microengineered 3D pulmonary interstitial mimetics highlight a critical role for matrix degradation in idiopathic pulmonary fibrosis

Fibrosis is often untreatable and is characterized by aberrant tissue scarring from activated myofibroblasts. Although the extracellular matrix becomes increasingly stiff and fibrous during disease progression, how these physical cues impact myofibroblast differentiation in 3D is poorly understood. Here we describe a multicomponent hydrogel that recapitulates the 3D fibrous structure hallmark to the interstitial tissue regions where idiopathic pulmonary fibrosis (IPF) initiates. In contrast to findings on 2D hydrogels, myofibroblast differentiation in 3D was inversely correlated with hydrogel stiffness, but positively correlated with matrix fiber density. Employing a multi-step bioinformatics analysis of IPF patient transcriptomes and in vitro pharmacologic screening, we identify matrix-metalloprotease activity to be essential for 3D but not 2D myofibroblast differentiation. Given our observation that compliant degradable 3D matrices amply support fibrogenesis, these studies demonstrate a departure from the established relationship between stiffness and myofibroblast differentiation in 2D, and provide a new 3D model for studying fibrosis.

bioengineering↗

bioRxiv2018

Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice

BACKGROUNDCadmium (Cd) is a toxic, pro-inflammatory metal ubiquitous in the diet that accumulates in body organs due to inefficient elimination. Many individuals exposed to dietary Cd are also infected by seasonal influenza virus. The H1N1 strain causes mild to severe pneumonia which can be fatal.\n\nOBJECTIVESTo determine the influence of low-dose Cd exposure on inflammatory responses to H1N1 influenza A virus.\n\nMETHODSWe exposed mice to low-dose (1 mg CdCl2/l) Cd or vehicle (water) for 16 weeks prior to infection with a sub-lethal dose of H1N1. Lung inflammation was assessed by histopathology and flow cytometry. We used a combination of transcriptomics, metabolomics and bioinformatics to determine the molecular associations of inflammatory cells important in Cd-exacerbated responses.\n\nRESULTSCd-treated mice had increased lung tissue inflammatory cells, including neutrophils, monocytes, T lymphocytes and dendritic cells, following H1N1 infection. Lung genetic responses to infection (increasing TNF-a, interferon and complement, and decreasing myogenesis) were also exacerbated. Global correlations with immune cell counts, leading edge gene transcripts and metabolites revealed that Cd increased correlation of myeloid immune cells with pro-inflammatory genes, particularly interferon-{gamma}, and metabolites in amino acid, nucleobase, glycerophospholipid and vitamin B3 pathways.\n\nDISCUSSIONCd burden in mice increased inflammation in response to sub-lethal H1N1 challenge, which was coordinated by genetic and metabolic responses, and could provide new targets for intervention against lethal inflammatory pathology of clinical H1N1 infection.

pharmacology and toxicology↗

bioRxiv2017

Quantifying and visualising divergence between pairs of phylogenetic trees: implications for phylogenetic reconstruction

Tree topologies are a primary output of phylogenetic analysis. It is important to understand how such outputs are influenced by the choice of phylogenetic method, and the nature and quality of input data. This often entails the measurement of how closely an output corresponds to an ideal tree topology. The symmetric difference (partition) metric is the only widely-used measure that is defined for trees that contain polytomies, but expresses undesirable behaviour in certain situations.\n\nHere I propose a divergence metric for unweighted tree topologies based on quartet statements, which measures the topological information common to two trees. This metric reflects the contributions of both accuracy and precision to tree quality; these components can be decomposed through the use of ternary diagrams. This approach is implemented in a new package for the R statistical environment, and applied to a recent controversy, where it provides a new perspective on the relative merits of Bayesian and parsimony approaches to morphological phylogenetics.

evolutionary biology↗

bioRxiv2017

Morphological phylogenetic analysis with inapplicable data

Non-independence of characters is a real phenomenon in phylogenetic data matrices, even though phylogenetic reconstruction algorithms generally assume character independence. In morphological datasets, the problem results in characters that cannot be applied to certain terminal taxa, with this inapplicability treated as \"missing data\" in a popular method of character coding. However, this treatment is known to create spurious tree length estimates on certain topologies, potentially leading to erroneous results in phylogenetic searches. Here we present a single-character algorithm for ancestral states reconstruction in datasets that have been coded using reductive coding. The algorithm uses up to four traversals on a tree to resolve final ancestral states - which are required in full before a tree can be scored. The algorithm employs explicit criteria for the resolution of ambiguity in applicable/inapplicable dichotomies and the optimization of missing data. We score trees following a previously published procedure that minimizes homoplasy over all characters. Our analysis of published datasets shows that, compared to traditional methods, our new method identifies different trees as \"optimal\"; as such, correcting for inapplicable data may significantly alter the outcome of tree searches.

evolutionary biology↗