Miracle-dz/UniFAR-FTUs huggingface dataset:
Cooperative foraging behavior during larval stage affects fitness in adult Drosophila

Cooperative behavior can confer advantages to animals. This is especially true for cooperative foraging which is thought to provide fitness benefits through more efficient acquisition and consumption of food. While examples of group foraging have been widely described, principles governing the formation of such aggregations as well as rules that determine cooperative group membership remain poorly understood. Here we take advantage of an experimental model system featuring cooperative foraging behavior in Drosophila. Under crowded conditions, fruit fly larvae form coordinated digging groups (clusters), in which individuals are linked together by sensory cues and stable group membership requires prior social experience. However, fitness benefits of Drosophila larval clustering remain to be determined. We demonstrate that when grown in crowded conditions on food that has been partially processed by other larvae, animals experience a developmental delay presumably due to the lesser nutrient value of the substrate. Intriguingly, these same conditions promote the formation of cooperative foraging clusters which further extends the larval stage compared to non-clustering animals. Remarkably, this developmental retardation also results in a relative increase in wing size, which is a good indicator of adult fitness. Thus, we find that the clustering-induced developmental delay is accompanied by adult fitness benefits. This suggests that foraging group membership provides advantages over solitary feeding in processed food. Therefore, cooperative behavior, while delaying development, may have evolved to give Drosophila larvae benefits when presented with competition for limited food resources.
A GRAB sensor reveals activity-dependent non-vesicular somatodendritic adenosine release

The purinergic signaling molecule adenosine (Ado) modulates many physiological and pathological brain functions,but its spatiotemporal release dynamics in the brain remains largely unknown. We developed a genetically encoded GPCR-Activation–Based Ado sensor (GRABAdo) in which Ado-induced changes in the human A2A receptor are reflected by fluorescence increases. This GRABAdo revealed that neuronal activity-induced extracellular Ado elevation was due to direct Ado release from somatodendritic regions of the neuron, requiring calcium influx through L-type calcium channels, rather than the degradation of extracellular ATP. The Ado release was slow (∼30 s) and depended on equilibrative nucleoside transporters (ENTs) rather than conventional vesicular release mechanisms. Thus, GRABAdo reveals an activity-dependent slow Ado release from somatodendritic region of the neuron, potentially serving modulating functions as a retrograde signal.
Do Parasites Reduce the Chances of Triangulation in a Real Food Web

At least ten different static patterns have been suggested by the analysis of food webs. However, the existence of many of these patterns has been questioned in recent years. One pattern that has remained immune from such criticism is intervality. In this paper, we develop a continuous measure of niche overlap, by calculating the number of non-triangulated quads (the simplest structure that confounds intervality) in a web. In contrast to intervality, this measure is applicable to webs of any size. We then explore the implications for niche overlap of including parasite - host links in a real food web, that of the Ythan estuary, Aberdeenshire. Increasing the number of parasite-host links increases the number of non-triangulated quads in a web. This increase is greater than that predicted by the cascade model. One explanation for the high incidence of intervality in real food webs is that species are ordered into a hierarchy dependent on body size. Parasites should obviate this ordering, since they are smaller than their hosts. Splitting the parasite species into 'trophospecies' according to their separate life history stages reduces the number of non-triangulated quads. This indicates that parasites do not reduce the chances of intervality (or increase the number of non-triangulated quads) merely because of their smaller body sizes, but because of their complex life cycles.
Stable gene expression for normalisation and single-sample scoring

Background Transcriptomic signatures are useful in defining the molecular phenotypes of cells, tissues, and patient samples. Their most successful and widespread clinical application is the stratification of breast cancer patients into molecular (PAM50) subtypes. In most cases, gene expression signatures are developed using transcriptome-wide measurements, thus methods that match signatures to samples typically require a similar degree of measurements. The cost and relatively large amounts of fresh starting material required for whole-transcriptome sequencing has limited clinical applications, and accordingly thousands of existing gene signatures are unexplored in a clinical context. Results Genes in a molecular signature can provide information about molecular phenotypes and their underlying transcriptional programs from tissue samples, however determining the transcriptional state of these genes typically requires the measurement of all genes across multiple samples to allow for comparison. An efficient assay and scoring method should quantify the relative abundance of signature genes with a minimal number of additional measurements. We identified genes with stable expression across a range of abundances, and with a preserved relative ordering across large numbers (thousands) of samples, allowing signature scoring, and supporting general data normalisation for transcriptomic data. Based on singscore, we have developed a new method, stingscore, which quantifies and summarises relative expression levels of signature genes from individual samples through the inclusion of these “stably-expressed genes”. Conclusion We show that our proposed list of stable genes has better stability across cancer and normal tissue data than previously proposed stable or housekeeping genes. Additionally, we show that signature scores computed from whole-transcriptome data are comparable to those calculated using only values for signature genes and our panel of stable genes. This new approach to gene expression signature analysis may facilitate the development of panel-type tests for gene expression signatures, thus supporting clinical translation of the powerful insights gained from cancer transcriptomic studies.
A histone-like motif in yellow fever virus contributes to viral replication

The mimicry of host proteins by viruses contributes to their ability to suppress antiviral immunity and hijack host biosynthetic machinery1. Host adaptation to evade this exploitation depends on host protein functional redundancy2. Non-redundant, essential host proteins have limited potential to adapt without severe consequences3. Histones, which are essential for genome architecture and control of gene expression, are among the most evolutionary conserved proteins4. Here we show that the capsid protein of the flavivirus yellow fever virus (YFV), mimics histone H4 and interferes with chromatin gene regulation by BRD4, a bromodomain and extraterminal domain (BET) protein. Two acetyl-lysine residues of YFV capsid are embedded in a histone-like motif that interacts with the BRD4 bromodomain, affecting gene expression and influencing YFV replication. These findings reveal histone mimicry as a strategy employed by an RNA virus that replicates in the cytosol5 and define convergent and distinct molecular determinants for motif recognition of the viral mimic versus histone H4.
Think Like an Expert: Neural Alignment Predicts Understanding in Students Taking an Introduction to Computer Science Course

How do students understand and remember new information? Despite major advances in measuring human brain activity during and after educational experiences, it is unclear how learners internalize new content, especially in real-life and online settings. In this work, we introduce a neural measure for predicting and assessing learning outcomes. Our approach hinges on the idea that successful learning involves forming the “right” set of neural representations, which are captured in “canonical” activity patterns shared across individuals. Specifically, we hypothesized that understanding is mirrored in “neural alignment”: the degree to which an individual learner’s neural representations match those of experts, as well as those of other learners. We tested this hypothesis in a longitudinal functional MRI study that regularly scanned college students enrolled in an introduction to computer science course. We additionally scanned graduate student “experts” in computer science. We found that alignment among students successfully predicted overall performance in a final exam. Furthermore, within individual students, concepts that evoked better alignment with the experts and with their fellow students were better understood, revealing neural patterns associated with understanding specific concepts. These results provide support for a novel neural measure of concept understanding that can be used to assess and predict learning outcomes in real-life contexts.
Limited time window for retinal gene therapy in a preclinical model of ciliopathy

Retinal degeneration is a common clinical feature of ciliopathies, a group of genetic diseases linked to ciliary dysfunction, and gene therapy is an attractive treatment option to prevent vision loss. Although the efficacy of retinal gene therapy is well established by multiple proof-of-concept preclinical studies, its long-term effect, particularly when treatments are given at advanced disease stages, is controversial. Incomplete treatment and intrinsic variability of gene delivery methods may contribute to the variable outcomes. Here, we used a genetic rescue approach to “optimally” treat retinal degeneration at various disease stages and examined the long-term efficacy of gene therapy in a mouse model of ciliopathy. We used a Bardet-Biedl syndrome type 17 (BBS17) mouse model, in which the gene-trap that suppresses Bbs17 (also known as Lztfl1) expression can be removed by tamoxifen administration, restoring normal gene expression systemically. Our data indicate that therapeutic effects of retinal gene therapy decrease gradually as treatments are given at later stages. These results suggest the presence of limited time window for successful gene therapy in certain retinal degenerations. Our study also implies that the long-term efficacy of retinal gene therapy may depend on not only the timing of treatment but also other factors such as the function of mutated genes and residual activities of mutant alleles.
Lack of Kcnn4 improves mucociliary clearance in muco-obstructive lung disease

Airway mucociliary clearance (MCC) is the main mechanism of lung defense keeping the airways free of infection and mucus obstruction. Airways surface liquid (ASL) volume, ciliary beating and mucus are central for proper MCC, and are critically regulated by sodium (Na+) absorption and anion secretion. Impaired MCC is a key feature of muco-obstructive disease. The calcium-activated potassium (K+)channel KCa.3. 1, encoded by the Kcnn4 gene, participates in intestinal ion secretion and previous studies showed that its activation increase Na+ absorption in airway epithelia, suggesting that hyperpolarization induced by KCa3.1 was sufficient to drive Na+ absorption. However, its role in airway epithelial function is not fully understood. We therefore aimed to elucidate the role of KCa3.1 in MCC in a genetically engineered mouse model. We show that KCa3.1 inhibition reduced Na+ absorption in mouse and human airway epithelium. Furthermore, the genetic deletion of Kcnn4 enhanced cilia beating frequency (CBF) and MCC ex vivo and in vivo. Kcnn4 was silenced in the Scnn1b-transgenic mouse (Scnn1btg/+), a model of muco-obstructive lung disease triggered by increased epithelial Na+-absorption, leading to improvements in MCC and reduction of Na+-absorption. KCa3.1 deletion did not change the amount of mucus but did reduce mucus adhesion, neutrophil infiltration and emphysema. Our data support that KCa3.1 inhibition attenuated muco-obstructive disease in the Scnn1btg/+ mice. K+-channel modulation may be a novel therapeutic strategy to treat muco-obstuctive lung diseases.
Targeting tumor necrosis factor α in psoriasis and psoriatic arthritis

Background: Psoriasis is an immune-mediated chronic inflammatory disease triggered and maintained by inflammatory mediators, including TNF-α. Objective/methods: To summarize the role of anti-TNF-α agents psoriasis therapy, focusing on the mechanisms and biological pathways involved, by reviewing relevant literature. Results/conclusions: The three TNF-α antagonists currently available (etanercept, infliximab and adalimumab) are effective in the therapy of psoriasis and psoriatic arthritis. Certolizumab pegol and golimumab are TNF-α inhibitors not approved for therapy of psoriasis yet. In addition to neutralizing soluble TNF-α, TNF-α blockers bind to membrane TNF-α and change the behavior of TNF-α-expressing cells, resulting in hastened cell cycle arrest and apopotosis, and suppresion of cytokine production. TNF-α blockers may also affect adaptive immune responses by reducing T helper cell (Th)1 and Th17 responses, and favoring the development of T-regulatory cells. TNF-α antagonists can regulate differentiation and activation of osteoclasts, thus reducing bone destruction in psoriatic arthritis. Anti-TNF-α agents differ in their pharmacokinetics and pharmacodinamic properties, which is reflected in their therapeutic and safety profiles. The safety of TNF-α antagonists has been established, and patient selection and monitoring allow risk minimization.
Fossil pigments as indicators of phototrophic response to salinity and climatic change in lakes of western Canada

High performance liquid chromatography was used to quantify changes in fossil pigments among 111 saline lakes in British Columbia and to reconstruct past changes in phototrophic communities in three closed-basin prairie lakes. Redundancy analysis of survey data demonstrated that pigment concentrations were greatest in deep stratified lakes but were unaffected by ion concentrations, pH, or conductivity. Algal standing crop (as chlorophyll) was correlated (r = 0.21n0.33, P < 0.01) only with fossil measures of total algal abundance (β-carotene, pheophytin a). In contrast, redundancy analysis demonstrated that relative abundance (%) of fossil carotenoids varied with lake chemistry. Luteinnzeaxanthin (from green algae, cyanobacteria) and diatoxanthin (diatoms) replaced fucoxanthin (diatoms, chrysophytes, dinoflagellates) as salinity increased, while alloxanthin (cryptophytes) and myxoxanthophyll (colonial cyanobacteria) were most common in lakes with low Ca 2+ and high dissolved organic carbon contents. Ordinations of surficial sediments suggested that post-deposition degradation did not alter the relation between pigment abundance and environmental characteristics. Fossil profiles of chlorophyll b and luteinnzeaxanthin also recorded climatic signals from Antelope and Kenosee lakes. These findings suggest that fossil pigments are well preserved in saline lakes and are capable of recording phototrophic community response to changes in salinity and climate.
A first perturbome of Pseudomonas aeruginosa: Identification of core genes related to multiple perturbations by a machine learning approach

Tolerance to stress conditions is vital for organismal survival, including bacteria under specific environmental conditions, antibiotics, and other perturbations. Some studies have described common modulation and shared genes during stress response to different types of disturbances (termed as perturbome), leading to the idea of central control at the molecular level. We implemented a robust machine learning approach to identify and describe genes associated with multiple perturbations or perturbome in a Pseudomonas aeruginosa PAO1 model. Using microarray datasets from the Gene Expression Omnibus (GEO), we evaluated six approaches to rank and select genes: using two methodologies, data single partition (SP method) or multiple partitions (MP method) for training and testing datasets, we evaluated three classification algorithms (SVM Support Vector Machine, KNN K-Nearest neighbor and RF Random Forest). Gene expression patterns and topological features at the systems level were included to describe the perturbome elements. We were able to select and describe 46 core response genes associated with multiple perturbations in P. aeruginosa PAO1 and it can be considered a first report of the P. aeruginosa perturbome. Molecular annotations, patterns in expression levels, and topological features in molecular networks revealed biological functions of biosynthesis, binding, and metabolism, many of them related to DNA damage repair and aerobic respiration in the context of tolerance to stress. We also discuss different issues related to implemented and assessed algorithms, including data partitioning, classification approaches, and metrics. Altogether, this work offers a different and robust framework to select genes using a machine learning approach.
A modular system regulates specialized metabolite pathway branch choice in the medicinal plant Catharanthus roseus

O_LICatharanthus roseus produces a diverse range of specialized metabolites of the monoterpenoid indole alkaloid (MIA) class in a heavily branched pathway. Recent great progress in identification of MIA biosynthesis genes revealed that the different pathway branch genes are expressed in a highly cell type- and organ-specific and stress-dependent manner. This implies a complex control by specific transcription factors (TFs), only partly revealed today. C_LIO_LIWe generated and mined a comprehensive compendium of publicly available C. roseus transcriptome data for MIA pathway branch-specific TFs. Functional analysis was performed through extensive comparative gene expression analysis and profiling of over 40 MIA metabolites in the C. roseus flower petal expression system. C_LIO_LIWe identified a MYB TF and additional members of the known BIS and ORCA regulators. Further detailed study of the ORCA TFs suggests subfunctionalization of ORCA paralogs in terms of branch-specific regulation and synergistic activity with the central jasmonate response regulator MYC2. Moreover, we identified specific amino acid residues within the ORCA DNA-binding domains that contribute to this branch-specific regulation. C_LIO_LIOur results advance our understanding of TF paralog specificity for which, despite the common occurrence of closely related paralogs in many species, comparative studies are scarce. C_LI
Transneuronal interactions facilitate axonal compartment formation

Precise connectivity of neurites to subcellular domains is a conserved feature of complex circuits, but the mechanisms defining precise wiring are largely unknown. The Drosophila mushroom-body is uniquely poised to study subcellular wiring as the adult γ-lobe harbors five distinct compartments, defined by localized innervations of other neuronal populations. Here we identify mechanisms required for precise wiring of γ-axons: Dpr12 and its interacting protein DIP-δ are both enriched at the γ4/5 compartments. However, while Dpr12 is cell-autonomously required in γ-neurons, DIP-δ acts in dopaminergic neurons for the formation of the γ4/5 compartments and the correct network architecture. Furthermore, γ-axons grow into regions preoccupied by DIP-δ+ neurons suggesting that they innervate a prepatterned lobe. Thus, transneuronal interactions that mediate precise wiring are required for axon compartmentalization. One Sentence Summary Transneuronal interactions instruct precise wiring that enables localized innervation by specific neurons to distinct axonal compartments.
Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells

The association of nuclear DNA with histones to form chromatin is essential to the temporal and spatial control of eukaryotic genomes. In this study, we examined the physical state of chromatin in vitro and in vivo. Our in vitro studies demonstrate that MgCl2-dependent self-association of native chromatin fragments or reconstituted nucleosomal arrays produced supramolecular condensates whose constituents are physically constrained and solid-like. Liquid chromatin condensates could be generated in vitro, but only using non-physiological conditions. By measuring DNA mobility within heterochromatin and euchromatin in living cells, we show that chromatin also exhibits solid-like behavior in vivo. Representative heterochromatin proteins, however, displayed liquid-like behavior and coalesced around a solid chromatin scaffold. Remarkably, both euchromatin and heterochromatin showed solid-like behavior even when transmission electron microscopy revealed limited interactions between chromatin fibers. Our results therefore argue that chromatin is not liquid but exists in a solid-like material state whose properties are tuned by fiber-fiber interactions.
The future of fire management in the British uplands

Prescribed and wild fires play a significant role in the ecology of upland areas; changes in the frequency and intensity of both can have significant effects on biodiversity and ecosystem function. Whilst the way we manage fire in the future will depend on desired outcomes, the risk of wildfires and the suitability of conditions for prescribed burning will depend on climate, land-use and environmental change. Changes in relative fire risk and hazard therefore need to be carefully considered when setting management policy. Fire has long been used as a management tool in the uplands of the UK but there has been little formal support or training, and emphasis has been placed on traditional knowledge. While there is pressure in some quarters for a reduction in the use of fire, prescribed burning can be used to protect biodiversity assets and reach a range of management objectives. Large areas of old heather excluded from rotational burning pose a significant fire hazard. Wildfires in such areas will be more intense and severe, and more likely to ignite peat, causing considerable environmental damage and releasing large quantities of carbon. We argue for an ecological basis for the use of fire and seek to open a debate by briefly reviewing the main controls on fire risk in upland areas and discussing existing management and its challenges with regards to three case studies: traditionally managed moorland, forestry and peatland soils. We make recommendations for future management and suggest significant challenges exist for managers and researchers that need to be dealt with urgently.