Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional diversity alters the effects of a pulse perturbation on the dynamics of tritrophic food webs

Biodiversity decline causes a loss of functional diversity, which threatens ecosystems through a dangerous feedback loop: this loss may hamper ecosystems’ ability to buffer environmental changes, leading to further biodiversity losses. In this context, the increasing frequency of climate and human-induced excessive loading of nutrients causes major problems in aquatic systems. Previous studies investigating how functional diversity influences the response of food webs to disturbances have mainly considered systems with at most two functionally diverse trophic levels. Here, we investigate the effects of a nutrient pulse on the resistance, resilience and elasticity of a tritrophic—and thus more realistic—plankton food web model depending on its functional diversity. We compare a non-adaptive food chain with no diversity to a highly diverse food web with three adaptive trophic levels. The species fitness differences are balanced through trade-offs between defense/growth rate for prey and selectivity/half-saturation constant for predators. We showed that the resistance, resilience and elasticity of tritrophic food webs decreased with larger perturbation sizes and depended on the state of the system when the perturbation occured. Importantly, we found that a more diverse food web was generally more resistant, resilient, and elastic. Particularly, functional diversity dampened the probability of a regime shift towards a non-desirable alternative state. In addition, despite the complex influence of the shape and type of the dynamical attractors, the basal-intermediate interaction determined the robustness against a nutrient pulse. This relationship was strongly influenced by the diversity present and the third trophic level. Overall, using a food web model of realistic complexity, this study confirms the destructive potential of the positive feedback loop between biodiversity loss and robustness, by uncovering mechanisms leading to a decrease in resistance, resilience and elasticity as functional diversity declines.
Microglial refinement of A-fibre projections in the postnatal spinal cord dorsal horn is required for normal maturation of dynamic touch

Sensory systems are shaped in postnatal life by the refinement of synaptic connections. In the dorsal horn of the spinal cord, sensory circuits undergo postnatal activity dependent reorganisation, including the retraction of primary afferent A-fibres from superficial to deeper laminae which is accompanied by decreases in cutaneous sensitivity. Here we show that microglia, the resident immune cells in the CNS, phagocytose A-fibre terminals in superficial laminae in the first weeks of life. Genetic perturbation of microglial engulfment at that time prevents the normal process of A-fibre retraction, resulting in increased sensitivity of dorsal horn cells to dynamic tactile cutaneous stimulation, and behavioural hypersensitivity to dynamic touch. Thus, functional microglia are necessary for normal postnatal development of dorsal horn sensory circuits. In the absence of microglial engulfment, superfluous A-fibre projections remain in the dorsal horn and the balance of sensory connectivity is disrupted, leading to lifelong hypersensitivity to dynamic touch. Impact statement Microglia phagocytose superfluous A-fibres in the superficial spinal dorsal horn during normal development, the disruption of which leads to long term aberrant dynamic touch processing and behaviour.
Methodological considerations when assessing mitochondrial respiration and biomarkers for mitochondrial content in human skeletal muscle

Background The assessment of mitochondrial respiration and mitochondrial content are two common measurements in the fields of skeletal muscle research and exercise science. However, to verify the validity of the observed changes in both mitochondrial respiration and mitochondrial content following an intervention such as exercise training, it is important to determine the reliability and reproducibility of the experimental design and/or techniques employed. We examined the repeatability of widely used methodologies for assessing mitochondrial respiration and mitochondrial content, respectively; the measurement of maximal mitochondrial oxidative phosphorylation in permeabilized muscle fibres using high-resolution respirometry, and the measurement of citrate synthase activity as a biomarker for mitochondrial content in a microplate with spectrophotometer. Result For mitochondrial respiration, the coefficient of variation for repeated measurements using muscle sampled from same biopsy decreased from 12.7% to 11% when measured in triplicate with outliers excluded, rather than in duplicate. The coefficient of variation was 9.7% for repeated muscle biopsies sampled across two separated days. For measurements of citrate synthase activity, the coefficient of variation was 3.5% of three technical repeats on the same plate, 10.2% for duplicate analyses using the same muscle lysate when conducted in the same day, and 30.5% when conducted four weeks apart. Conclusion We have provided evidence for important technical considerations when measuring mitochondrial respiration with human skeletal muscle: 1) the relatively large technical variability can be reduced by increasing technical repeats and excluding outliers; 2) the biological variability and absolute mitochondrial respiration value of the participants should be considered when estimating the required sample size; 3) a new threshold of 15% for the increase in respiration rate after the addition of cytochrome c test for testing mitochondrial outer membrane integrity. When analysing citrate synthase activity, our evidence suggests it is important to consider the following: 1) all samples from the same study should be homogenized and measured at the same time using the same batch of freshly made chemical reagents; 2) biological variability should be considered when detecting small change in mitochondrial content; 3) the relative change should be used to compare the outcomes from different studies.
Performance of generalist hemiparasitic Euphrasia across a phylogenetically diverse host spectrum

Generalist hemiparasites may attach to many different host species and experience complex parasite-host interactions. How these parasite-host interactions impact on the fitness of hemiparasitic plants remain largely unknown. We used experimentally tractable eyebrights (Euphrasia, Orobanchaceae) to understand parasite-host interactions affecting the performance of a generalist hemiparasitic plant. Common garden experiments were carried out measuring Euphrasia performance across 45 diverse hosts and in different parasite-host combinations. We showed that variation in hemiparasite performance could be attributed mainly to host species and host phylogenetic relationships (λ = 0.82; 0.17-1.00 Cl). When this variation in performance is broken down temporally, annual host species cause earlier flowering, and lead to poorer performance late in the season. While Euphrasia species typically perform similarly on a given host species, some eyebrights show more specialised parasite-host interactions. Our results show that generalist hemiparasites only benefit from attaching to a limited, but phylogenetically divergent, subset of hosts. The conserved responses of divergent Euphrasia species suggest hemiparasite performance is affected by common host attributes. However, evidence for more complex parasite-host interactions show that a generalist hemiparasite can potentially respond to individual host selection pressures and may adapt to local host communities.
gen3sis: the general engine for eco-evolutionary simulations on the origins of biodiversity

Understanding the origins of biodiversity has been an aspiration since the days of early naturalists. The immense complexity of ecological, evolutionary and spatial processes, however, has made this goal elusive to this day. Computer models serve progress in many scientific fields, but in the fields of macroecology and macroevolution, eco-evolutionary models are comparatively less developed. We present a general, spatially-explicit, eco-evolutionary engine with a modular implementation that enables the modelling of multiple macroecological and macroevolutionary processes and feedbacks across representative spatio-temporally dynamic landscapes. Modelled processes can include environmental filtering, biotic interactions, dispersal, speciation and evolution of ecological traits. Commonly observed biodiversity patterns, such as α, β and γ diversity, species ranges, ecological traits and phylogenies, emerge as simulations proceed. As a case study, we examined alternative hypotheses expected to have shaped the latitudinal diversity gradient (LDG) during the Earth’s Cenozoic era. We found that a carrying capacity linked with energy was the only model variant that could simultaneously produce a realistic LDG, species range size frequencies, and phylogenetic tree balance. The model engine is open source and available as an R-package, enabling future exploration of various landscapes and biological processes, while outputs can be linked with a variety of empirical biodiversity patterns. This work represents a step towards a numeric and mechanistic understanding of the physical and biological processes that shape Earth’s biodiversity.
Tissue flow through pores: a computational study

Cell migration is of major importance for the understanding of phenomena such as morphogenesis, cancer metastasis, or wound healing. In many of these situations cells are under external confinement. In this work we show by means of computer simulations with a Cellular Potts Model (CPM) that the presence of a bottleneck in an otherwise straight channel has a major influence on the internal organisation of an invading cellular monolayer and the motion of individual cells therein. Comparable to a glass or viscoelastic material, the cell sheet is found to exhibit features of both classical solids and classical fluids. The local ordering on average corresponds to a regular hexagonal lattice, while the relative motion of cells is unbounded. Compared to an unconstricted channel, we observe that a bottleneck perturbs the formation of regular hexagonal arrangements in the epithelial sheet and leads to pile-ups and backflow of cells near the entrance to the constriction, which also affects the overall invasion speed. The scale of these various phenomena depends on the dimensions of the different channel parts, as well as the shape of the funnel domain that connects wider to narrower regions.
FPM app: an open-source application for simple and intuitive Fourier ptychographic reconstruction

Summary Fourier ptychographic microscopy (FPM) is a computational microscopy technique that enables large field of view and high-resolution microscopic imaging of biological samples. However, the FPM does not yet have an adequately capable open-source software. In order to fill this gap we are presenting novel, simple, universal, semi-automatic and highly intuitive graphical user interface (GUI) open-source application called the FPM app enabling wide-scale robust FPM reconstruction. Apart from implementing the FPM in accessible GUI app, we also made several improvements in the FPM image reconstruction process itself, making the FPM more automatic, noise-robust and faster. Availability and Implementation FPM app was implemented in MATLAB and all MATLAB codes along with standalone executable version of the FPM app and the online documentation are freely accessible at https://github.com/MRogalski96/FPM-app. Our exemplary FPM datasets may be downloaded at https://bit.ly/2MxNpGb.
Effects of stochasticity on the length and behaviour of ecological transients

There is a growing recognition that ecological systems can spend extended periods of time far away from an asymptotic state, and that ecological understanding will therefore require a deeper appreciation for how long ecological transients arise. Recent work has defined classes of deterministic mechanisms that can lead to long transients. Given the ubiquity of stochasticity in ecological systems, a similar systematic treatment of transients that includes the influence of stochasticity is important. Stochasticity can of course promote the appearance of transient dynamics by preventing systems from settling permanently near their asymptotic state, but stochasticity also interacts with deterministic features to create qualitatively new dynamics. As such, stochasticity may shorten, extend, or fundamentally change a system’s transient dynamics. Here, we describe a general framework that is developing for understanding the range of possible outcomes when random processes impact the dynamics of ecological systems over realistic time scales. We emphasize that we can understand the ways in which stochasticity can either extend or reduce the lifetime of transients by studying the interactions between the stochastic and deterministic processes present, and we summarize both the current state of knowledge and avenues for future advances.
A baton-relay and proofreading mechanism for selective ER retrieval signal capture by the KDEL receptor

The KDEL-retrieval pathway captures escaped ER proteins with a KDEL or variant C-terminal signal at acidic pH in the Golgi and releases them at neutral pH in the ER. To address the mechanism of signal binding and the molecular basis for differences in signal affinity, we determined the HDEL and RDEL bound structures of the KDEL-receptor. Affinity differences are explained by interactions between the variable −4 position of the signal and W120, whereas initial capture of retrieval signals by their carboxyl-terminus is mediated by a baton-relay mechanism involving a series of conserved arginine residues in the receptor. This explains how the signal is first captured and then pulled into the binding cavity. During capture, retrieval signals undergo a selective proofreading step involving two gatekeeper residues D50 and E117 in the receptor. These mechanisms operate upstream of the pH-dependent closure of the receptor and explain the selectivity of the KDEL-retrieval pathway.
Quantitative blood flow estimation in vivo by optical speckle image velocimetry

Speckle based methods are popular non-invasive, label-free full-field optical techniques for imaging blood flow maps at single vessel resolution with a high temporal resolution. However, conventional speckle approach cannot provide an absolute velocity map with magnitude and direction. Here, we report a novel optical speckle image velocimetry (OSIV) technique for measuring the quantitative blood flow vector map by utilizing particle image velocimetry with speckle cross-correlations. We demonstrate that our OSIV instrument has a linearity range up to 7 mm/s, higher than conventional optical methods. Our method can measure the absolute flow vector map at up to 190 Hz without sacrificing the image size, and it eliminates the need for a high-speed camera/detector. We applied OSIV to image the blood flow in a mouse brain, and as a proof of concept, imaged the real-time dynamic changes in the cortical blood flow field during the stroke process in vivo. Our wide-field quantitative flow measurement OSIV method without the need of tracers provides a valuable tool for studying the healthy and diseased brain.
Early life stress is associated with earlier emergence of permanent molars

Exposure to adversity can accelerate biological aging. However, existing biomarkers of early aging are either costly and difficult to collect, like epigenetic signatures, or cannot be detected until late childhood, like pubertal onset. We evaluated the hypothesis that early adversity is associated with earlier molar eruption, an easily assessed measure that has been used to track the length of childhood across primates. In a preregistered analysis (n = 117, ages 4 to 7 y), we demonstrate that lower family income and exposure to adverse childhood experiences (ACEs) are significantly associated with earlier eruption of the first permanent molars, as rated in T2-weighted magnetic resonance images (MRI). We replicate relationships between income and molar eruption in a population-representative dataset (National Health and Nutrition Examination Survey; n = 1,973). These findings suggest that the impact of stress on the pace of biological development is evident in early childhood, and detectable in the timing of molar eruption.
A novel method for generating 3D constructs with branched vascular networks using multi-materials bioprinting and direct surgical anastomosis

Vessels pervade almost all body tissues, and significantly influence the pathophysiology of human body. Previous attempts to establish multi-scale vascular connection and function in 3D model tissues using bioprinting have had limited success due to the incoordination between cell-laden materials and stability of the perfusion channel. Here, we report a methodology to fabricate centimetre-scale vascularized soft tissue with high viability and accuracy using multi-materials bioprinting involving inks with low viscosity and a customized multistage-temperature-control printer. The tissue formed was perfused with branched vasculature with well-formed 3D capillary network and lumen, which would potentially supply the cellular components with sufficient nutrients in the matrix. Furthermore, the same methodology was applied for generating liver-like tissue with the objective to fabricate and mimic a mature and functional liver tissue, with increased functionality in terms of synthesis of liver specific proteins after in vitro perfusion and in vivo subperitoneal transplantation in mice. Moreover, to establish immediate blood perfusion, an elastic layer was printed wrapping sacrificial ink to support the direct surgical anastomosis of the carotid artery to the jugular vein. Our findings highlight the support extended by vasculature network in soft hydrogels which helps to sustain the thick and dense cellularization in engineered tissues.
A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts

Background Excessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242). Results MonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS, pmodel=4.55E-08, px2 =7.80E-08) and in the Veteran Aging Cohort Study (VACS, pmodel=1.85E-02, px2 =3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Women’s Interagency HIV Study (WIHS, β=-2.63, px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks. Conclusions We observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based “clock” in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.
Mugs and Plants: Object Semantic Knowledge Alters Perceptual Processing With Behavioral Ramifications

Neural processing of objects with action associations recruits dorsal visual regions more than the neural processing of objects without such associations. We hypothesized that because the dorsal and ventral visual pathways have differing proportions of magno- and parvocellular input, there should be behavioral differences in perceptual tasks between manipulable and nonmanipulable objects. This hypothesis was tested in college-age adults across five experiments (Ns = 26, 26, 30, 25, and 25) using a gap-detection task, suited to the spatial resolution of parvocellular processing, and an object-flicker-discrimination task, suited to the temporal resolution of magnocellular processing. Directly predicted from the cellular composition of each pathway, a strong nonmanipulable-object advantage was observed in gap detection, and a small manipulable-object advantage was observed in flicker discrimination. Additionally, these effects were modulated by reducing object recognition through inversion and by suppressing magnocellular processing using red light. These results establish perceptual differences between objects dependent on semantic knowledge.
DrugComb update: a more comprehensive drug sensitivity data repository and analysis portal

Combinatorial therapies that target multiple pathways have shown great promises for treating complex diseases. DrugComb (https://drugcomb.org/) is a web-based portal for the deposition and analysis of drug combination screening datasets. Since its first release, DrugComb has received continuous updates on the coverage of data resources, as well as on the functionality of the web server to improve the analysis, visualization and interpretation of drug combination screens. Here we report significant updates of DrugComb, including: 1) manual curation and harmonization of more comprehensive drug combination and monotherapy screening data, not only for cancers but also for other diseases such as malaria and COVID-19; 2) enhanced algorithms for assessing the sensitivity and synergy of drug combinations; 3) network modelling tools to visualize the mechanisms of action of drugs or drug combinations for a given cancer sample; and 4) state-of-the-art machine learning models to predict drug combination sensitivity and synergy. These improvements have been provided with more user-friendly graphical interface and faster database infrastructure, which make DrugComb the most comprehensive web-based resources for the study of drug sensitivities for multiple diseases.