Miracle-dz/UniFAR-FTUs huggingface dataset:
No Brain Signature of Prediction Error to Unattended Visual Stimuli Despite Early Brain Encoding of the Stimuli

Prediction error is a basic component of predictive-coding theory of brain processing. According to the theory, each stage of brain processing of sensory information generates a model of the current sensory input; subsequent input is compared against the model and only if there is a mismatch, a prediction error, is further processing performed. Recently, Smout et al. [1] found that a signature of prediction error, the visual (v) mismatch negativity (MMN), for a fundamental property of visual input—its orientation—was absent without attention on the stimuli. This is remarkable because the weight of evidence for MMNs from audition and vision is that they occur without attention. To resolve this discrepancy, we conducted an experiment addressing two alternative explanations for Smout et al.’s finding: that it was from a lack of reproducibility or that participants’ visual systems did not encode the stimuli when attention was on something else. We conducted a similar experiment to Smout et al.’s. We showed 21 participants sequences of identically oriented Gabor patches, standards, and, unpredictably, otherwise identical, Gabor patches differing in orientation by ±15°, ±30°, and ±60°, deviants. To test whether participants encoded the orientation of the standards, we varied the numbers of standards preceding a deviant, allowing us to search for a decrease in activity with the number of repetitions of standards—repetition suppression. We diverted participants’ attention from the oriented stimuli with a central, letter-detection task. We reproduced Smout et al.’s finding of no vMMN without attention, strengthening their finding. We also found that our participants showed repetition suppression: they did encode the stimuli pre-attentively. We also found early processing of deviants. We discuss whether this earlier processing of deviants may be why no further processing, in the vMMN time window, occurs.
Region- and variance-based DNA methylation analyses reveal novel disease genes and pathways for systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with unclear pathogenesis. DNA methylation is an important regulatory mechanism on gene expression, providing a key angle to understand disease mechanisms. To understand the pathways involved in SLE, and to develop biomarkers for its diagnosis and treatment, we analyzed DNA methylation profiles on blood cells from SLE patients and healthy controls. Results We identified most differentially methylated regions (DMRs) in T cells, while majority of differentially variable sites (DVSs) were found in B cells, featuring hypervariability in enhancers. We observed a prominent T cell receptor (TCR) signaling cluster with consistent hypermethylation and a B cell receptor (BCR) cluster with highly increased variability in SLE. Genes involved in innate immunity were often found hypomethylated, while adaptive immunity genes were featured with hypermethylation. Using a machine learning approach, we identified 60 genes that accurately distinguished SLE patients from healthy individuals, which also showed correlation with disease activities. Conclusions This study highlights the role of lymphocyte receptor aberrations in the disease and identified a list of genes showing great potential as biomarkers and shedding new light on disease mechanisms, through novel analyses of methylation data.
Not all pathways are the same – unique adaptations to submerged environments emerge from comparative seagrass genomics

Seagrasses are an ecologically important group of plants that have returned to the sea from terrestrial ancestors on at least three occasions (Cymodoceaceae, Posidoniaceae, Zosteraceae). Seagrass-specific genomic adaptations to marine life are known from the Zosteraceae. However, independent lineages may have devised different solutions to life underwater. Here, we present two new genome assemblies from endemic Australian seagrasses, Amphibolis antarctica (Cymodoceaceae) and Posidonia australis (Posidoniaceae). We found large differences in genome size between Amphibolis and Posidonia driven by repeat expansion in Posidonia. We show that parts of ethylene pathways known to be lost in Zosteraceae are partially retained in older seagrass lineages (Cymodoceaeceae and Posidoniaceae). We describe adaptations within salinity, disease resistance, cell wall, and photosynthesis-related pathways not shared with other seagrasses. These findings provide insight into the impact of recolonising marine environments on formerly terrestrial plant genomes, with some adaptations previously thought to be universal to marine living not having occurred in A. antarctica and P. australis.
Structure-function dynamics of engineered, modular neuronal networks with controllable afferent-efferent connectivity

Objective. Microfluidic devices interfaced with microelectrode arrays have in recent years emerged as powerful platforms for studying and manipulating in vitro neuronal networks at the micro- and mesoscale. By segregating neuronal populations using microchannels only permissible to axons, neuronal networks can be designed to mimic the highly organized, modular topology of neuronal assemblies in the brain. However, little is known about how the underlying topological features of such engineered neuronal networks contribute to their functional profile. To start addressing this question, a key parameter is control of afferent or efferent connectivity within the network. Approach. In this study, we show that a microfluidic device featuring axon guiding channels with geometrical constraints inspired by a Tesla valve effectively promotes unidirectional axonal outgrowth between neuronal nodes, thereby enabling us to control afferent connectivity. Main results. Our results moreover indicate that these networks exhibit a more efficient network organization with higher modularity compared to single nodal controls. We verified this by applying designer viral tools to fluorescently label the neurons to visualize the structure of the networks, combined with extracellular electrophysiological recordings using embedded nanoporous microelectrodes to study the functional dynamics of these networks during maturation. We furthermore show that electrical stimulations of the networks induce signals selectively transmitted in a feedforward fashion between the neuronal populations. Significance. A key advantage with our microdevice is the ability to longitudinally study and manipulate both the structure and function of neuronal networks with high accuracy. This model system has the potential to provide novel insights into the development, topological organization, and neuroplasticity mechanisms of neuronal assemblies at the micro- and mesoscale in healthy and perturbed conditions.
Closure of "Dynamic Response of Arbitrarily Shaped Foundations: Experimental Verification"

Results of twenty-one free vibration tests on surface model footings on moist sand having different base shapes and about equal base area have been reported. These tests are used here to verify the analytical method of the companion paper, for circular, square and rectangular base shapes with aspect ratios up to 6, and including vertical, torsional and coupled swaying-rocking oscillations. Close agreement is found between predicted and measured frequencies in all cases, and also between damping ratios in vertical and torsional vibration. The experiments provide strong support for the vertical and torsional radiation damping graphs developed in the companion paper, including verification of the increased damping ratios predicted for the longest footings. The accord is also reasonably good for damping in those swaying-rocking tests in which rocking and material damping are dominant and the overall damping ratio is about 3%. However, the method overpredicts the measured swaying-rocking damping ratios in those tests in which swaying and radiation damping are also important, and for which larger damping ratios are predicted (4% to 9%). This discrepancy between half-space predicted swaying-rocking damping and measured values is explained by the effect of boundary wave reflections on the test results.
The Cation/H+ exchanger OsCAX2 is involved in cadmium tolerance and accumulation through vacuolar sequestration in rice

Excessive cadmium (Cd) in rice grains is a serious food safety problem. The development of Cd-safe varieties requires the identification of germplasms and genes with major effect on Cd accumulation but without negative effects on other important traits. Here, we reported that OsCAX2, a member of the rice Cation/H+ exchanger (CAX) family, is an important Cd transporter. OsCAX2 encodes a tonoplast-localized protein and is strongly upregulated by Cd, mainly expresses in root exodermis, parenchyma in cortex, endodermis and stele cells. Depletion of OsCAX2 resulted in enhanced Cd sensitivity and root-to-shoot translocation in rice, while overexpression of OsCAX2 significantly increased Cd tolerance and reduced Cd transport by promoting root Cd influx and vacuolar storage, which ultimately reduced Cd transport via xylem. OsCAX2 also had significant effects on tissues/organs distribution of Cd but had no effects on grain yield and agronomic traits. Importantly, the OsCAX2 overexpressing lines had more than 70% lower grain Cd accumulation, increased iron (Fe), zinc (Zn) and manganese (Mn) and reduced copper (Cu) accumulation. Therefore, OsCAX2 is an ideal gene for developing Cd-safe rice varieties via transgenic approach.
Sequence type diversity amongst antibiotic-resistant bacterial strains is lower than amongst antibiotic-susceptible strains

The increasing number of antibiotic resistant bacterial infections is a global threat to human health. Antibiotic resistant bacterial strains generally evolve from susceptible strains by either horizontal gene transfer or chromosomal mutations. After evolving within a host, such resistant strains can be transmitted to other hosts and increase in frequency in the population at large. Population genetic theory postulates that the increase in frequency of an adaptive trait can lead to signatures of selective sweeps. One would thus expect to observe reduced genetic diversity amongst that part of the population that carries the adaptive trait. Specifically, if the evolution of new resistant strains is rare, it is expected that resistant strains represent only a subset of the diversity of susceptible strains. It is currently unknown if diversity of resistant strains is indeed lower than diversity of susceptible strains when considering antibiotic resistance. Here we show that in several bacterial species in several different datasets, sequence-type diversity amongst antibiotic-resistant bacterial strains is indeed lower than amongst antibiotic-susceptible strains in most cases. We re-analysed eight existing clinical datasets with Escherichia coli, Staphylococcus aureus and Enterococcus faecium samples. These datasets consisted of 53 - 1094 patient samples, with multi-locus sequence types and antibiotic resistance phenotypes for 3 - 19 different antibiotics. Out of 59 comparisons, we found that resistant strains were significantly less diverse than susceptible strains in 51 cases (86%). In addition, we show that sequence-type diversity of antibiotic-resistant strains is lower if resistance is rare, compared to when resistance is common, which is consistent with rare resistance being due to fewer evolutionary origins. Our results show that for several different bacterial species, we observe reduced diversity of resistant strains, which is consistent with the evolution of resistance driven by selective sweeps stemming from a limited number of evolutionary origins. In future studies, more detailed analysis of such sweep signatures is warranted.
Brain criticality predicts individual synchronization levels in humans

Moderate levels of synchronization of neuronal oscillations are essential for healthy brain dynamics. Synchronization levels exhibit large inter-individual variability the origins of which are unknown. Neuronal systems have been postulated to operate near a critical transition point or in an extended regime between disorder (subcritical) and order (supercritical phase) characterized by moderate synchronization and emergent power-law long-range temporal correlations (LRTCs). We investigated whether inter-individual variability in synchronization levels is explained by the individual position along the critical regime by analyzing magnetoencephalography (MEG) and intra-cerebral stereo-electroencephalography (SEEG) human resting-state data. Here we show that variability in synchronization levels exhibits a positive linear and quadratic relationships with LRTCs in healthy participants and brain areas. In the epileptogenic zone this correlation was negative. These results show that variability in synchronization levels is regulated by the individual position along an extended critical-like regime, with healthy brain areas tending to operate in its subcritical and epileptogenic areas in its supercritical side.
Re-evaluating management of established pests including the European wasp, Vespula germanica using biocontrol agents

Established pests such as the European wasp (Vespula germanica) are often overlooked as candidates for management programmes (eradication and/or containment) because the use of traditional surveillance and control techniques over very large areas becomes uneconomic. Use of biological control agents that persist in the environment is usually the only economically feasible option, however the processes around approvals for release of biocontrol agents can take significant amounts of time and resources, especially if screening and testing of potential agents is required. This project investigates whether the European wasp could be a candidate for a renewed management programme in south-eastern Australia given the availability of a biocontrol agent following successful screening and testing of an agent, Sphecophaga vesparum vesparum, in the 1980s. Whether a biological control programme is worthwhile pursuing depends on the size of the benefits to industry, community and the environment from a reduction in European wasp abundance. This project explores the benefits and costs of European wasp management using a biocontrol agent, and importantly, includes valuation of the social and environmental impacts of the pest.
The structural basis of the multi-step allosteric activation of Aurora B kinase

Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.
The synergistic anti-Warburg efficacy of temozolomide, metformin and epigallocatechin gallate in glioblastoma

Background An important hallmark of glioblastoma aggressiveness is its altered metabolism of glucose. This metabolic shift wherein the tumor cells employ aerobic glycolysis regardless of oxygen availability via reprogramming of mitochondrial oxidative phosphorylation is known as the Warburg effect. Previous literatures have linked this metabolic reprograming to tumor progression glioblastoma cell proliferation making it a key target for targeted drug therapy. Objective To evaluate the anti-Warburg efficacies of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in preclinical glioblastoma models. Methodology Based on this lacuna, the current study aimed to explore the therapeutic efficacy of the triple-drug combination of temozolomide, metformin and epigallocatechin gallate in attenuating Warburg effect and glucose uptake in glioblastoma both in vitro and in vivo. Results Our results showed that the triple-drug combination had significantly reduced glucose uptake and reversed the Warburg effect in glioblastoma cells and in the xenograft-induced glioma rat model. Conclusion Thus, the triple-drug combination would serve as an effective therapeutic regime to hamper glioblastoma progression via altering glucose metabolism and improve the overall prognosis in patient setting.
Neighbourhood species richness and drought-tolerance traits modulate tree growth and δ13C responses to drought

Mixed-species forests are promoted as a forest management strategy for climate change adaptation, but whether they are more resistant to drought than monospecific forests remains contested. Particularly, the trait-based mechanisms driving the role of tree diversity under drought remain elusive. Using tree cores from a large-scale biodiversity experiment, we investigated tree growth and physiological stress responses (i.e. increase in wood carbon isotopic ratio; δ13C) to changes in climate-induced water availability (wet to dry years) along gradients in neighbourhood tree species richness and drought-tolerance traits. We hypothesized that neighbourhood species richness increases growth and decreases δ13C and that these relationships are modulated by the abiotic (i.e. climatic conditions) and the biotic context. We characterized the biotic context using drought-tolerance traits of focal trees and their neighbours. These traits are related to cavitation resistance vs resource acquisition and stomatal control. Tree growth increased with neighbourhood species richness. However, we did not observe a universal relief of water stress in species-rich neighbourhoods. Neighbourhood species richness effects on growth and δ13C did not strengthen from wet to dry years. Instead, richness-growth and richness-δ13C relationships were modulated by climatic conditions and the traits of trees and their neighbours. At either end of each drought-tolerance gradient, species responded in opposing directions during drought and non-drought years. We show that species’ drought-tolerance traits can explain the strength and nature of biodiversity-ecosystem functioning relationships in experimental tree communities experiencing drought. Mixing tree species can increase growth but may not universally relieve drought stress. One-sentence summary The drought-tolerance traits of trees and their neighbours determine biodiversity-ecosystem functioning relationships in experimental tree communities.
A new eight‐node quadrilateral shear‐bending plate finite element

A new Reissner-Mindlin plate finite element for the very thin and thick plates without locking and spurious zero-energy modes is presented. The element has very good convergence characteristics both for thin and thick plates, is hardly insensitive to mesh distortions, and passes the patch tests. The formulation of the element is derived from a displacement variational principle and some general criteria to compute inconsistent transverse shear strains. These criteria have been applied with success to four- and eight-node quadrilateral plate finite elements and could be applied to construct triangular elements
The RNA Binding proteome of axonal mRNAs in sympathetic neurons

Background Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their cytoarchitecture. Targeting of RNA transcripts to axons is one of the mechanisms that allows rapid local translation of proteins in response to extracellular signals. 3’ untranslated regions (UTRs) of mRNA are non-coding sequences that play a critical role in determining transcript localisation and translation by interacting with specific RNA binding proteins (RBPs). However, how 3’UTRs contribute to mRNA metabolism and the nature of RBP complexes responsible for these functions remain elusive. Results We performed 3’ end sequencing of RNA isolated from axons and cell bodies of sympathetic neurons exposed to either Nerve Growth factor (NGF) or Neurotrophin 3 (NT3). NGF and NT3 are growth factors essential for sympathetic neuron development that act through distinct signalling mechanisms. Whereas NT3 is thought to act only locally, NGF signals back from axons to the cell bodies. We discovered that both NGF and NT3 affect transcription and alternative polyadenylation and induce the localisation of specific 3’UTR isoforms to axons. The finding that many transcripts with short 3’UTR were detected only in axons suggest that these may undergo local post-transcriptional remodelling. The integration of our data with CLIP-sequencing data revealed that long 3’UTR isoforms associate with RBP complexes in the nucleus, and once in axons, regulate cytoplasmic 3’ UTR isoform cleavage into shorter isoform. Conclusions Our findings shed new light on the complex interplay between nuclear polyadenylation, mRNA localisation and local 3’UTR remodelling in developing neurons. Graphical abstract
Multiplexed selectivity screening of anti-GPCR antibodies

G protein-coupled receptors (GPCRs) control critical cellular signaling pathways. Therapeutic agents, such as antibodies (Abs), are being developed to modulate GPCR signaling pathways. However, validating the selectivity of anti-GPCR Abs is challenging due to sequence similarities of individual receptors within GPCR subfamilies. To address this, we developed a multiplexed immunoassay to test >400 anti-GPCR Abs from the Human Protein Atlas targeting a customized library of 215 expressed and solubilized GPCRs representing all GPCR subfamilies. We found that ~61% of Abs were selective for their intended target, ~11% to bind off-target, and ~28% not to bind any GPCR. Antigens of on-target Abs were, on average, significantly longer, more disordered, and less likely to be buried in the interior of the GPCR protein than the other Abs. These results provide important insights into the immunogenicity of GPCR epitopes and form a basis for the design of therapeutic Abs and the detection of pathological auto-antibodies. TEASER A multiplexed library-to-library selectivity analysis of 400 anti-GPCR antibodies within subfamilies of 200 solubilized receptors.
Dynamics of systematic errors in the NMC Medium Range Forecast model

Abstract A simple error vorticity model is used to study processes contributing to the evolution of the 300-hPa systematic nondivergent flow errors in the National Meteorological Center Medium Range Forecast model (MRF) during the 1992–93 winter season. The error model is forced by two source terms representing, respectively, systematic errors in the irrotational flow and transient eddy vorticity fluxes. The results indicate that the model simulates reasonably well the development of many of the large-scale features of the zonally asymmetric part of the MRF systematic nondivergent flow errors, but it fails to simulate the zonally symmetric portion unless an extra forcing term representing systematic errors in the irrotational flow analyses is included. Two independent methods are employed to estimate the systematic errors in the irrotational flow analyses. The two estimates are highly correlated, and both indicate that the analyzed irrotational flow in the Tropics is too weak. The magnitude of the estimat.