Lower resting brain entropy is associated with stronger task activation and deactivation.

Brain entropy (BEN) calculated from resting state fMRI has been the subject of increasing research interest in recent years. Previous studies have shown the correlations between rest BEN and neurocognition and task performance, but how this relates to task-evoked brain activations and deactivations remains unknown. The purpose of this study is to address this open question using large data (n = 862). Voxel wise correlations were calculated between rest BEN and task activations/deactivations of five different tasks. For most of the assessed tasks, lower rest BEN was found to be associated with stronger activations (negative correlations) and stronger deactivations (positive correlations) only in brain regions activated or deactivated by the tasks. Higher workload evoked spatially more extended negative correlations between rest BEN and task activations. These results not only confirm that resting brain activity can predict brain activity during task performance but also for the first time show that resting brain activity may facilitate both task activations and deactivations. In addition, the results provide a clue to understanding the individual differences of task performance and brain activations.

Greater male than female variability in regional brain structure across the lifespan.

For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

When I'm 64: Age-Related Variability in Over 40,000 Online Cognitive Test Takers.

OBJECTIVES: Age-related differences in cognition are typically assessed by comparing groups of older to younger participants, but little is known about the continuous trajectory of cognitive changes across age, or when a shift to older adulthood occurs. We examined the pattern of mean age differences and variability on episodic memory and executive function measures over the adult life span, in a more fine-grained way than past group or life-span comparisons. METHOD: We used a sample of over 40,000 people aged 18-90 who completed psychometrically validated online tests measuring episodic memory and executive functions (the Cogniciti Brain Health Assessment). RESULTS: Cognitive performance declined gradually over adulthood, and rapidly later in life on spatial working memory, processing speed, facilitation (but not interference), associative recognition, and set shifting. Both polynomial and segmented regression fit the data well, indicating a nonlinear pattern. Segmented regression revealed a shift from gradual to rapid decline that occurred in the early 60s. Variability between people (interindividual variability or diversity) and variability within a person across tasks (intraindividual variability or dispersion) also increased gradually until the 60s, and rapidly after. Confirmatory factor analysis revealed a single general factor (of variance shared between tasks) offered a good fit for performance across tasks. DISCUSSION: Life-span cognitive performance shows a nonlinear pattern, with gradual decline over early and mid-adulthood, followed by a transition in the 60s to notably accelerated, but more variable, decline. Some people show less decline than others, and some cognitive abilities show less within-person decline than others.

Context-specific activations are a hallmark of the neural basis of individual differences in general executive function.

Common executive functioning (cEF) is a domain-general factor that captures shared variance in performance across diverse executive function tasks. To investigate the neural mechanisms of individual differences in cEF (e.g., goal maintenance, biasing), we conducted the largest fMRI study of multiple executive tasks to date (N = 546). Group average activation during response inhibition (antisaccade task), working memory updating (keep track task), and mental set shifting (number-letter switch task) overlapped in classic cognitive control regions. However, there were no areas across tasks that were consistently correlated with individual differences in cEF ability. Although similar brain areas are recruited when completing different executive function tasks, activation levels of those areas are not consistently associated with better performance. This pattern is inconsistent with a simple model in which higher cEF is associated with greater or less activation of a set of control regions across different task contexts; however, it is potentially consistent with a model in which individual differences in cEF primarily depend on activation of domain-specific targets of executive function. Brain features that explain commonalities in executive function performance across tasks remain to be discovered.

Phenotypic Switching and Filamentation in Candida haemulonii, an Emerging Opportunistic Pathogen of Humans.

Phenotypic plasticity is a common strategy adopted by fungal pathogens to adapt to diverse host environments. Candida haemulonii is an emerging multidrug-resistant human pathogen that is closely related to Candida auris. Until recently, it was assumed that C. haemulonii is incapable of phenotypic switching or filamentous growth. In this study, we report the identification of three distinct phenotypes in C. haemulonii: white, pink, and filament. The white and pink phenotypes differ in cellular size, colony morphology, and coloration on phloxine B- or CuSO4-containing agar. Switching between the white and pink cell types is heritable and reversible and is referred to as "the primary switching system." The additional switch phenotype, filament, has been identified and exhibits obviously filamentous morphology when grown on glycerol-containing medium. Several unique characteristics of the filamentous phenotype suggest that switching from or to this phenotype poses as a second yeast-filament switching system. The yeast-filament switch is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote filament-yeast transition. We further demonstrated that numerous aspects of the distinct cell types differ in numerous biological aspects, including their high temperature response, specific gene expression, CuSO4 tolerance, secreted aspartyl protease (SAP) activity, and virulence. Therefore, transition among the three phenotypes could enable C. haemulonii to rapidly adapt to, survive, and thrive in certain host niches, thereby contributing to its virulence. IMPORTANCE The capacity to switch between distinct cell types, known as phenotypic switching, is a common strategy adopted by Candida species to adapt to diverse environments. Despite considerable studies on phenotypic plasticity of various Candida species, Candida haemulonii is considered to be incapable of phenotypic switching or filamentous growth. Here, we report and describe filamentation and three distinct phenotypes (white, pink, and filament) in C. haemulonii. The three cell types differ in cellular and colony appearance, gene expression profiles, CuSO4 tolerance, and virulence. C. haemulonii cells switch heritably and reversibly between white and pink cell types, which is referred to as the "primary switching system." Switching between pink and filamentous phenotypes is nonheritable and temperature-dependent, representing a second switching system. As in other Candida species, switching among distinct morphological types may provide C. haemulonii with phenotypic plasticity for rapid responses to the changing host environment, and may contribute to its virulence.

Inter-individual variability in structural brain development from late childhood to young adulthood.

A fundamental task in neuroscience is to characterize the brain's developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined inter-individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0-26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable inter-individual variability in the magnitude of changes observed for all examined brain measures. The majority of individuals demonstrated decreases in total gray matter volume, cortex volume, mean cortical thickness, and white matter surface area in mid-adolescence, with more variability present during the transition into adolescence and the transition into early adulthood. While most individuals demonstrated increases in white matter volume in early adolescence, this shifted to a majority demonstrating stability starting in mid-to-late adolescence. We observed sex differences in these patterns, and also an association between the size of an individual's brain structure and the overall rate of change for the structure. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.

Data integration uncovers the metabolic bases of phenotypic variation in yeast.

The relationship between different levels of integration is a key feature for understanding the genotype-phenotype map. Here, we describe a novel method of integrated data analysis that incorporates protein abundance data into constraint-based modeling to elucidate the biological mechanisms underlying phenotypic variation. Specifically, we studied yeast genetic diversity at three levels of phenotypic complexity in a population of yeast obtained by pairwise crosses of eleven strains belonging to two species, Saccharomyces cerevisiae and S. uvarum. The data included protein abundances, integrated traits (life-history/fermentation) and computational estimates of metabolic fluxes. Results highlighted that the negative correlation between production traits such as population carrying capacity (K) and traits associated with growth and fermentation rates (Jmax) is explained by a differential usage of energy production pathways: a high K was associated with high TCA fluxes, while a high Jmax was associated with high glycolytic fluxes. Enrichment analysis of protein sets confirmed our results. This powerful approach allowed us to identify the molecular and metabolic bases of integrated trait variation, and therefore has a broad applicability domain.

Neural processing of vision and language in kindergarten is associated with prereading skills and predicts future literacy.

The main objective of this longitudinal study was to investigate the neural predictors of reading acquisition. For this purpose, we followed a sample of 54 children from the end of kindergarten to the end of second grade. Preliterate children were tested for visual symbol (checkerboards, houses, faces, written words) and auditory language processing (spoken words) using a passive functional magnetic resonance imaging paradigm. To examine brain-behavior relationships, we also tested cognitive-linguistic prereading skills at kindergarten age and reading performance of 48 of the same children 2 years later. Face-selective response in the bilateral fusiform gyrus was positively associated with rapid automatized naming (RAN). Response to both spoken and written words at preliterate age was negatively associated with RAN in the dorsal temporo-parietal language system. Longitudinally, neural response to faces in the ventral stream predicted future reading fluency. Here, stronger neural activity in inferior and middle temporal gyri at kindergarten age was associated with higher reading performance. Our results suggest that interindividual differences in the neural system of language and reading affect literacy acquisition and thus might serve as a marker for successful reading acquisition in preliterate children.

Herbaceous perennial plants with short generation time have stronger responses to climate anomalies than those with longer generation time.

There is an urgent need to synthesize the state of our knowledge on plant responses to climate. The availability of open-access data provide opportunities to examine quantitative generalizations regarding which biomes and species are most responsive to climate drivers. Here, we synthesize time series of structured population models from 162 populations of 62 plants, mostly herbaceous species from temperate biomes, to link plant population growth rates (λ) to precipitation and temperature drivers. We expect: (1) more pronounced demographic responses to precipitation than temperature, especially in arid biomes; and (2) a higher climate sensitivity in short-lived rather than long-lived species. We find that precipitation anomalies have a nearly three-fold larger effect on λ than temperature. Species with shorter generation time have much stronger absolute responses to climate anomalies. We conclude that key species-level traits can predict plant population responses to climate, and discuss the relevance of this generalization for conservation planning.

The power of modelling pulsatile profiles.

The quantitative description of individual observations in non-linear mixed effects models over time is complicated when the studied biomarker has a pulsatile release (e.g. insulin, growth hormone, luteinizing hormone). Unfortunately, standard non-linear mixed effects population pharmacodynamic models such as turnover and precursor response models (with or without a cosinor component) are unable to quantify these complex secretion profiles over time. In this study, the statistical power of standard statistical methodology such as 6 post-dose measurements or the area under the curve from 0 to 12 h post-dose on simulated dense concentration-time profiles of growth hormone was compared to a deconvolution-analysis-informed modelling approach in different simulated scenarios. The statistical power of the deconvolution-analysis-informed approach was determined with a Monte-Carlo Mapped Power analysis. Due to the high level of intra- and inter-individual variability in growth hormone concentrations over time, regardless of the simulated effect size, only the deconvolution-analysis informed approach reached a statistical power of more than 80% with a sample size of less than 200 subjects per cohort. Furthermore, the use of this deconvolution-analysis-informed modelling approach improved the description of the observations on an individual level and enabled the quantification of a drug effect to be used for subsequent clinical trial simulations.

24-Hour Ambulatory Blood Pressure Variability in Children with Obstructive Sleep Apnea.

OBJECTIVE: To evaluate blood pressure (BP) variability in 24-hour ambulatory BP monitoring in children with obstructive sleep apnea (OSA). STUDY DESIGN: Case series study. METHODS: Children aged 4 to 16 years with clinical symptoms were recruited in a tertiary medical center. Overnight polysomnography and 24-hour recordings of ambulatory BP were performed for each child. The severity of OSA was classified as primary snoring (apnea-hypopnea index [AHI] < 1), mild OSA (1 ≤ AHI < 5), moderate OSA (10 > AHI ≥ 5), and severe OSA (AHI ≥ 10). The standard deviation of mean BP was used as an indicator of BP variability. RESULTS: A total of 550 children were included (mean age: 7.6 years; 70% were boys; 20% were obese). Compared with the children with primary snoring, children with severe OSA exhibited significantly higher nighttime systolic BP (108.0 vs. 100.5 mmHg, P < .001), nighttime diastolic BP (58.9 vs 55.6 mmHg, P = .002), nighttime mean arterial pressure (75.3 vs. 70.5 mmHg, P < .001), nighttime systolic BP load (40.5% vs. 25.0%, P < .001), nighttime diastolic BP load (25.3% vs. 12.9%, P < .001), and nighttime systolic BP variability (11.4 vs. 9.6, P = .001). Multiple linear regression analyses revealed an independent association between AHI and nighttime systolic BP variability (regression coefficient = 0.31, 95% CI = 0.06-0.56, P = .015) after adjustment for age, gender, adiposity, and hypertensive status. CONCLUSIONS: OSA in children is associated with increased BP and BP variability. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2126-2132, 2021.

Individual differences in interoceptive accuracy and prediction error in motor functional neurological disorders: A DTI study.

In motor functional neurological disorders (mFND), relationships between interoception (a construct of high theoretical relevance to its pathophysiology) and neuroanatomy have not been previously investigated. This study characterized white matter in mFND patients compared to healthy controls (HCs), and investigated associations between fiber bundle integrity and cardiac interoception. Voxel-based analysis and tractography quantified fractional anisotropy (FA) in 38 mFND patients compared to 38 HCs. Secondary analyses compared functional seizures (FND-seiz; n = 21) or functional movement disorders (n = 17) to HCs. Network lesion mapping identified gray matter origins of implicated fiber bundles. Within-group mFND analyses investigated relationships between FA, heartbeat tracking accuracy and interoceptive trait prediction error (discrepancies between interoceptive accuracy and self-reported bodily awareness). Results were corrected for multiple comparisons, and all findings were adjusted for depression and trait anxiety. mFND and HCs did not show any between-group interoceptive accuracy or FA differences. However, the FND-seiz subgroup compared to HCs showed decreased integrity in right-lateralized tracts: extreme capsule/inferior fronto-occipital fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, and thalamic/striatum to occipital cortex projections. These alterations originated predominantly from the right temporoparietal junction and inferior temporal gyrus. In mFND patients, individual differences in interoceptive accuracy and interoceptive trait prediction error correlated with fiber bundle integrity originating from the insula, temporoparietal junction, putamen and thalamus among other regions. In this first study investigating brain-interoception relationships in mFND, individual differences in interoceptive accuracy and trait prediction error mapped onto multimodal integration-related fiber bundles. Right-lateralized limbic and associative tract disruptions distinguished FND-seiz from HCs.

Why do humans have unique auditory event-related fields? Evidence from computational modeling and MEG experiments.

Auditory event-related fields (ERFs) measured with magnetoencephalography (MEG) are useful for studying the neuronal underpinnings of auditory cognition in human cortex. They have a highly subject-specific morphology, albeit certain characteristic deflections (e.g., P1m, N1m, and P2m) can be identified in most subjects. Here, we explore the reason for this subject-specificity through a combination of MEG measurements and computational modeling of auditory cortex. We test whether ERF subject-specificity can predominantly be explained in terms of each subject having an individual cortical gross anatomy, which modulates the MEG signal, or whether individual cortical dynamics is also at play. To our knowledge, this is the first time that tools to address this question are being presented. The effects of anatomical and dynamical variation on the MEG signal is simulated in a model describing the core-belt-parabelt structure of the auditory cortex, and with the dynamics based on the leaky-integrator neuron model. The experimental and simulated ERFs are characterized in terms of the N1m amplitude, latency, and width. Also, we examine the waveform grand-averaged across subjects, and the standard deviation of this grand average. The results show that the intersubject variability of the ERF arises out of both the anatomy and the dynamics of auditory cortex being specific to each subject. Moreover, our results suggest that the latency variation of the N1m is largely related to subject-specific dynamics. The findings are discussed in terms of how learning, plasticity, and sound detection are reflected in the auditory ERFs. The notion of the grand-averaged ERF is critically evaluated.

Quality of Life in Patients with Neuroendocrine Neoplasms: The Role of Severity, Clinical Heterogeneity, and Resilience.

CONTEXT: Although health-related quality of life (HRQoL) is a fundamental outcome in oncological clinical trials, its evaluation in the neuroendocrine neoplasm (NEN) research field is still limited. OBJECTIVES: This study assessed the role of clinical severity (ie, presence or absence of metastasis and lines of therapies) and heterogeneity (ie, primary site, types of therapy, biology, and surgery) of NEN in relation to HRQoL, as well as resilience as a moderator between clinical severity and HRQoL. DESIGN: Cross-sectional multicentric study. SETTING: Italian university hospitals. PATIENTS: A total of 99 Italian patients (53 men and 46 women) with NEN and ranged in age from 22-79 years old. MAIN OUTCOME MEASURE: Severity and heterogeneity of NENs, HRQoL, and resilience. RESULTS: The presence of metastasis and a greater number of therapies affected the global health and some physical symptoms. Resilience was associated with global health, functional status, and some physical symptoms, and it moderated the impact of metastases on constipation and of the multiple therapies on diarrhea and financial problems. Patients with NEN in districts other than the gastroenteropancreatic system and those in follow-up perceived fewer physical symptoms than their counterparts. Patients with a sporadic NEN perceived their functional status, global health, and disease-related worries as better than those with a hereditary NEN. Patients who underwent surgery were lower in constipation than their counterparts. CONCLUSION: These findings highlight the need to assess the relationships between the clinical severity and heterogeneity of NEN with HRQoL and the role of resilience in improving patients' HRQoL.

Influence of ageing on circadian rhythm of heart rate variability in healthy subjects.

BACKGROUND: The analysis of the circadian rhythm of heart rate variability (HRV) represents a relevant physiological tool to assess the vagal system. However, the influence of age (mostly >75 years) on HRV is not widely known. AIMS: The aim of this study was to evaluate the influence of age on HRV, particularly in the elderly and to identify a model of this relationship. The study was carried out by examining linear and nonlinear parameters extracted from HRV, including individuals over 75 years for which there is no research available. METHODS: Data from 140 healthy subjects were sex matched and divided into young (young group: 15-39 years old), adult (adult group: 40-64 years old) and senior (senior group: 65-90 years old) groups. 24-h Holter monitoring was used and several HRV parameters were extracted from time, and spectral and nonlinear analyses were examined. RESULTS: Time-domain parameters, mainly standard deviation of the NN interval (SDNN) and number of successive differences of intervals which differ by more than 50 ms, presented significant differences between the young group and the other two groups during the 24-h period, while normalized spectral parameters (LFn, HFn and low frequency/high frequency), as well as nonlinear parameters, mainly ß exponent and fractal dimension, showed significant difference between the senior group and the other two groups. All these parameters showed a similar circadian rhythm with significant differences between the mean day and night values, especially in young and adult group cohorts. Moreover, a parabolic relationship between these parameters and age was highlighted with an opposite trend over about 60 years compared with younger people. CONCLUSION: A progressive physiological autonomic imbalance is present in ageing. The inverse trend in the relation between HRV parameters and age found in the senior group could be mainly due to a faster fluctuation of RR. This should be considered when studying changes in the cardiac autonomic nervous control.

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P<0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (rspearman=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

YAP/TAZ deficiency reprograms macrophage phenotype and improves infarct healing and cardiac function after myocardial infarction.

Adverse cardiac remodeling after myocardial infarction (MI) causes structural and functional changes in the heart leading to heart failure. The initial post-MI pro-inflammatory response followed by reparative or anti-inflammatory response is essential for minimizing the myocardial damage, healing, and scar formation. Bone marrow-derived macrophages (BMDMs) are recruited to the injured myocardium and are essential for cardiac repair as they can adopt both pro-inflammatory or reparative phenotypes to modulate inflammatory and reparative responses, respectively. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are the key mediators of the Hippo signaling pathway and are essential for cardiac regeneration and repair. However, their functions in macrophage polarization and post-MI inflammation, remodeling, and healing are not well established. Here, we demonstrate that expression of YAP and TAZ is increased in macrophages undergoing pro-inflammatory or reparative phenotype changes. Genetic deletion of YAP/TAZ leads to impaired pro-inflammatory and enhanced reparative response. Consistently, YAP activation enhanced pro-inflammatory and impaired reparative response. We show that YAP/TAZ promote pro-inflammatory response by increasing interleukin 6 (IL6) expression and impede reparative response by decreasing Arginase-I (Arg1) expression through interaction with the histone deacetylase 3 (HDAC3)-nuclear receptor corepressor 1 (NCoR1) repressor complex. These changes in macrophages polarization due to YAP/TAZ deletion results in reduced fibrosis, hypertrophy, and increased angiogenesis, leading to improved cardiac function after MI. Also, YAP activation augmented MI-induced cardiac fibrosis and remodeling. In summary, we identify YAP/TAZ as important regulators of macrophage-mediated pro-inflammatory or reparative responses post-MI.

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression.

Epithelial mesenchymal transition (EMT) is a complex process through which epithelial (E) cells lose their adherens junctions, transform into mesenchymal (M) cells and attain motility, leading to metastasis at distant organs. Nowadays, the concept of EMT has shifted from a binary phase of interconversion of pure E to M cells and vice versa to a spectrum of E/M transition states preferably coined as hybrid/partial/intermediate EMT. Hybrid EMT, being a plastic transient state, harbours cells which co-express both E and M markers and exhibit high tumourigenic properties, leading to stemness, metastasis, and therapy resistance. Several preclinical and clinical studies provided the evidence of co-existence of E/M phenotypes. Regulators including transcription factors, epigenetic regulators and phenotypic stability factors (PSFs) help in maintaining the hybrid state. Computational and bioinformatics approaches may be excellent for identifying new factors or combinations of regulatory elements that govern the different EMT transition states. Therapeutic intervention against hybrid E/M cells, though few, may evolve as a rational strategy against metastasis and drug resistance. This review has attempted to present the recent advancements on the concept and regulation of the process of hybrid EMT which generates hybrid E/M phenotypes, evidence of intermediate EMT in both preclinical and clinical setup, impact of partial EMT on promoting tumourigenesis, and future strategies which might be adapted to tackle this phenomenon.

High-throughput, image-based phenotyping reveals nutrient-dependent growth facilitation in a grass-legume mixture.

This study used high throughput, image-based phenotyping (HTP) to distinguish growth patterns, detect facilitation and interpret variations to nutrient uptake in a model mixed-pasture system in response to factorial low and high nitrogen (N) and phosphorus (P) application. HTP has not previously been used to examine pasture species in mixture. We used red-green-blue (RGB) imaging to obtain smoothed projected shoot area (sPSA) to predict absolute growth (AG) up to 70 days after planting (sPSA, DAP 70), to identify variation in relative growth rates (RGR, DAP 35-70) and detect overyielding (an increase in yield in mixture compared with monoculture, indicating facilitation) in a grass-legume model pasture. Finally, using principal components analysis we interpreted between species changes to HTP-derived temporal growth dynamics and nutrient uptake in mixtures and monocultures. Overyielding was detected in all treatments and was driven by both grass and legume. Our data supported expectations of more rapid grass growth and augmented nutrient uptake in the presence of a legume. Legumes grew more slowly in mixture and where growth became more reliant on soil P. Relative growth rate in grass was strongly associated with shoot N concentration, whereas legume RGR was not strongly associated with shoot nutrients. High throughput, image-based phenotyping was a useful tool to quantify growth trait variation between contrasting species and to this end is highly useful in understanding nutrient-yield relationships in mixed pasture cultivations.