bluuebunny/crossref_metadata_2025 huggingface dataset:
Mature larvae continue calling at night inVespa mandariniafrom laboratory observations
Authors: Fujioka Haruna , Saga Tatsuya
Published: September 2024

Animals produce and perceive vibroacoustic signals.Vespahornet larvae produce a rhythmic ‘rasping’ sound by rubbing their mandibles against the cell wall of the nest. The call is thought to be a larval provisioning cue. However, detailed observations of larval calls have been limited to a few species, and it is not known whether the call can be influenced by the external environment, such as light and time of day, or by internal larval states, such as feeding. We conducted laboratory observations of larval calls under workerless conditions to investigate the effects of 1) larval stage, 2) daily variation, 3) light conditions, and 4) feeding treatment.Vespa mandarinialarvae produce sounds regardless of their situation, such as position, light condition, time of day, and worker absence. During mastication, the larvae stopped calling. A key finding of this research is the novel discovery that larvae produce sounds at night, which is a previously undocumented behaviour.
The size-weight illusion and beyond: a new model of perceived weight
Authors: Pisu Veronica , Graf Erich W. , Adams Wendy J.
Published: September 2024

In the size-weight illusion (SWI), the smaller of two same-weight, same apparent material objects is perceived as heavier. The SWI has proved difficult to explain via traditional Bayesian models, which predict the opposite effect: expected weight from size (smaller = lighter) should be integrated with felt weight, such that the smaller object should be perceptually lighter. Other authors have proposed that weight and density are combined according to Bayesian principles, or that Bayesian models incorporating efficient coding can predict the SWI via ‘likelihood repulsion’. These models, however, have been evaluated only under the narrow conditions of typical SWI stimuli. Here we establish a general model of perceived weight for pairs of objects that differ in weight and / or density and / or size by varying amounts. In a visuo-haptic task, participants (N = 30) grasped and lifted pairs of cubes, and reported their perceived heaviness. We report that the SWI occurs even at very small density differences, repudiating the idea that the illusion requires a significant conflict between expected and felt weight. Across all object pairs, perceived weight was well explained by a model (R2= .98) that includes a positive influence of both objects’ weights and the judged object’s density, but a negative influence of the other object’s density. Critically, the influence of both densities on perceived weight is strongly modulated by weight difference, being three times as large for zero / small weight differences than large differences. Thus, it is only under the unusual conditions of typical SWI studies that we confuse weight with density to a substantial extent. Unlike existing models, that are inconsistent with our more comprehensive dataset, our model provides a quantitative, accurate and generalised account of weight perception for pairs of objects across various weight and size conditions.

Author summary

Knowing how heavy an object is allows us to grasp and lift it efficiently and without mishaps. Surprisingly, humans make systematic errors when judging the weight of objects of different size. For example, when two objects differ in size but have identical weight, the smaller object feels heavier. This is the ‘size-weight illusion’. The illusion is strong and reliable and occurs even when we know that the two objects actually have the same weight. The size-weight illusion demonstrates that the human perceptual system doesn’t work like a weighing scale, but instead takes into account other object features such as size or density, alongside weight. In this paper, we present a model that allows us to predict perceived weight in the size-weight illusion and across a wide range of objects of different weight / size / density, where previous models have failed.
Cancer Cell Removing Using a Reinforcement Learning Agent
Authors: Mousavi Fard Ali
Published: September 2024

Cancer cell is a deadly problem which is the main cause of global death. Unfortunately, the conventional therapies like chemo/radio therapy are not viable ways to remove all of the cancer cells. Although Robotic achievements have been increased in cancer therapy, these devices do not have the decision-making ability to grasp their environment like biologists. In this paper, a cancer cell removing method based on Artificial Intelligence techniques is introduced. The proposed idea adopts a combination of object detection and reinforcement model in order to detect the cancer cells and take some actions to remove them. To implement this idea, YOLOv9 is trained on a cancer cell image dataset to detect and segment the cancer cell and create a set point for RL model then in the next step, Soft Actor Critic (SAC) is considered as a RL model to grasp the desired environment and take some appropriate actions to reach the target. The experimental result of this model shows that the proposed model can be adopted in different cancer therapy robots like micro/wireless soft robots to boost their performance in terms of their decision-making ability.
Extinction potential from invasive alien species
Authors: Philippe-Lesaffre Martin , Arbieu Ugo , Bang Alok , Camacho Morelia , Cuthbert Ross N. , Genovesi Piero , Kumschick Sabrina , Pili Arman , Seebens Hanno , Wang Shengyu , Latombe Guillaume
Published: September 2024

Biological invasions pose significant threats to biodiversity, while impacting ecosystem services, human health, and cultural heritage. Despite these far-ranging effects, their impacts are generally underappreciated by both the public and policymakers, resulting in insufficient management and inadequate conservation outcomes. Recognizing the gap in effective quantitative measurement tools, we introduce the Extinction Potential Metric (EPM) and its derivative, EPM for Unique species (EPM-U; adjusted for phylogenetic uniqueness) to quantify the ecological damage caused by invasive alien species (IAS). These metrics estimate the number of current and projected extinct species within a 50-year horizon under a business-as-usual scenario due to specific IAS.

We applied EPM and EPM-U to assess threats to native terrestrial vertebrates from IAS, examining impacts on 2178 amphibians, 920 birds, 865 reptiles, and 473 mammals. The analysis identified that damage mostly stems from a limited number of IAS, notably two pathogenic fungi affecting amphibians (up to 380 equivalent extinct species) and primarily cats (139 equivalent extinct species) and rats (50 equivalent extinct species) impacting other groups, through mechanisms such as predation, disease, and reduced reproductive success in birds.

The proposed metrics not only provide a standardised measure of ecological impacts but are sufficiently versatile to be tailored for specific spatial and temporal scales or taxonomic groups. Furthermore, EPM could serve as a model for developing unified indicators to monitor global biodiversity targets, such as those defined in the Kunming-Montreal Global Biodiversity Framework (GBF), by assessing the ecological effects of various individual and combined anthropogenic stresses. Also, EPM and EPM-U could support the enforcement of Target 6 of the GBF, by establishing lists of IAS requiring urgent prevention and control. Thus, EPM and EPM-U offer critical tools for improving the management of biological invasions and enhancing global conservation strategies.
Improved method for detecting protein-protein interactions using proximity ligation assay
Authors: Tower Zach , Chang Hao
Published: September 2024

Proximity ligation assay has been widely used to detect protein-protein interaction in cells and tissues. While with great sensitivity, its specificity was often neglected. Here, we report the existence of varying levels of false positives observed with this assay and provide suggestions to minimize false positives for more accurate detection of protein-protein interactions, especially for membrane proteins.
Climate change worry and the association with future depression and anxiety: cross-national analysis of 11 European countries
Authors: Collery A. , Niedzwiedz C.L.
Published: September 2024

BACKGROUND

Climate change is one of the biggest threats to global health and can affect people’s mental health directly and indirectly. This study focused on the implications of climate change worry for mental health.

OBJECTIVE

To determine the association between climate change worry and future risk of depression, anxiety and sleep disturbance across 11 European countries.

METHODS

The study included 5,155 participants in the European Social Survey-10 (2020-22), which assessed climate change worry and subsequent follow-up CROss-National Online Survey 2 (CRONOS-2) wave 4, which measured symptoms of depression and anxiety (2022). Overall relationships between climate change worry and risk of depression, anxiety and sleep disturbance were explored using logistic regression models adjusting for potential confounders, then stratified by country.

FINDINGS

Climate change worry was associated with increased risk of anxiety (OR: 1.38, 95% CI: 1.13-1.68), but not depression (OR: 1.10, 95% CI: 0.94-1.29) or sleep disturbance (OR: 1.08, 95% CI: 0.92-1.27), in pooled analyses across countries. When stratified by country, climate worry had differing associations with the outcomes, with the strongest relationships between climate worry and anxiety found in Slovenia and Italy.

CONCLUSIONS

Climate change worry may contribute to clinically significant anxiety in some countries, but less so for depression and sleep disturbance.

CLINICAL IMPLICATIONS

Strategies to cope with climate change anxiety are needed as it does not align with traditional mental health models. Further research is needed to design and evaluate interventions and policies to support mental health in the context of climate change.

What is already known on this topic

Climate anxiety is a growing concern as the implications of climate change become more evident. Few studies have assessed how climate worry is related to mental health problems and research in this area is limited by methodological concerns, such as non-representative samples and cross-sectional studies.

What this study adds

Levels of climate-related worry vary across Europe, with the highest levels observed in Portugal, Austria and Slovenia, and lowest in Sweden, Iceland and Italy. Overall, climate worry was associated with future risk of clinical levels of anxiety, but not depression or sleep problems. In stratified analyses, the strongest associations were found for anxiety in Slovenia and Italy.

How this study might affect research, practice or policy

The mental health implications of climate change should be considered in both health and climate policies. Further research is required to assess country and regional-level factors which may affect the relationship between climate worry and mental health and potential causal effects investigated.
Determinants of self-treatment with antimalarials in Ndola district, Zambia: a cross-sectional study
Authors: Susiku Namasiku Grace , Jacobs Choolwe , Zgambo Jessy , Kaonga Patrick , Sitali Lungowe
Published: September 2024

Antimalarial drug resistance has been an obstacle in the fight against malaria over the years. Antimalarial self-medication is one of the factors associated with antimalarial resistance, and is on the rise globally and has become quite common among developing populations. Self-medication is when individuals choose and use medications to treat symptoms they perceive or diagnose themselves, without the guidance of a healthcare professional. This study aimed at investigating prevalence and determinants of antimalarial drug self-medication among adults in Ndola district, Zambia. A cross-sectional study was conducted among adults in Ndola district, Zambia in June 2023. Using multistage cluster sampling, 446 participants were randomly selected and interviewed through a mobile-based structured questionnaire administered by the researchers using Kobo collect/kobo toolbox. The head of household was the primary participant. Data was then exported to Microsoft Excel, cleaned and coded, and thereafter exported to STATA version 16.1 for analysis. Chi-square tests and logistic regression analysis was used to test associations between categorical variables and to estimate the odds of antimalarial drug self-medication associated with the explanatory variables. The prevalence of antimalarial drug self-medication was 20% in this study population and the factors significantly associated were; moderate to mild illness, bad experience with hospital care, lack of knowledge about antimalarial drug resistance, and the perception that antimalarial drug self-medication was not risky. The finding that antimalarial self-medication was common in this study population is suggestive of a poor state of the health-care delivery system possibly due to inadequate manpower, stock out of drugs in health facilities, and lack of awareness about the risks of self-medication. This further suggests that there is great need for regulatory authorities to strengthen drug regulations and update the list of over-the-counter and essential medicines to ensure the safety of public health. In addition, authorities should repackage malaria sensitization messages to strongly highlight the risks of antimalarial drug self-medication.
Mating strategy explains sex-biased infections in an emerging fungal disease
Authors: Kailing Macy J. , Hoyt Joseph R. , White J. Paul , Redell Jennifer A. , Kaarakka Heather M. , Langwig Kate E.
Published: September 2024

Mating dynamics can govern species impacts from rapid global change by influencing population rates of growth and adaptation, as well as individual traits that affect mortality risks from novel pressures.

Here, we examined sex differences in mating phenology ofMyotis lucifugusto understand how reproductive strategies contribute to disease impacts as the mating season coincides with exposure to a lethal fungal pathogen,Pseudogymnoascus destructans. We expected differences in activity among sexes to modify seasonal disease dynamics asP. destructanscan replicate only at the cool temperatures at which bats hibernate.

We used passive antenna systems installed at the entrances of hibernacula and PIT tags to characterize activity patterns of bats impacted by white-nose syndrome. We also measured pathogen loads on bats during autumn mating and early hibernation to assess how infection severity changed according to host phenology.

We found that females spent fewer days active during autumn, arrived after males, and were primarily active on the warmest nights. Males remained highly active throughout the mating period and later in autumn than females. Importantly, these differences in mating phenology corresponded to more severe infections in females during early hibernation as male activity, and thus warm body temperatures, inhibit pathogen growth.

Differences in activity between sexes and in the transition from swarm to hibernation likely reflects males maximizing their mating opportunities while females conserve energy to meet the cost of spring migration and reproduction. More broadly, our results show how mating phenology can contribute to sex-biased impacts of a novel disease and highlight the value of understanding species’ mating systems to anticipate the impacts of environmental change.
Wnt5a and Notum Influence the Temporal Dynamics of Cartilaginous Mesenchymal Condensations in Developing Trachea
Authors: Bottasso-Arias Natalia , Mohanakrishnan Megha , Trovillion Sarah , Burra Kaulini , Russell Nicholas X. , Wu Yixin , Xu Yan , Sinner Debora
Published: September 2024

The trachea is essential for proper airflow to the lungs for gas exchange. Frequent congenital tracheal malformations affect the cartilage, causing the collapse of the central airway during the respiratory cycle. We have shown that Notum, a Wnt ligand de-acylase that attenuates the canonical branch of the Wnt signaling pathway, is necessary for cartilaginous mesenchymal condensations. In Notum deficient tracheas, chondrogenesis is delayed, and the tracheal lumen is narrowed. It is unknown if Notum attenuates non-canonical Wnt signaling. We observed premature tracheal chondrogenesis after mesenchymal deletion of the non-canonical Wnt5a ligand. We hypothesize that Notum and Wnt5a are required to mediate the timely formation of mesenchymal condensations, giving rise to the tracheal cartilage. Ex vivo culture of tracheal tissue shows that chemical inhibition of the Wnt non-canonical pathway promotes earlier condensations, while Notum inhibition presents delayed condensations. Furthermore, non- canonical Wnt induction prevents the formation of cartilaginous mesenchymal condensations. On the other hand, cell-cell interactions among chondroblasts increase in the absence of mesenchymal Wnt5a. By performing an unbiased analysis of the gene expression in Wnt5a and Notum deficient tracheas, we detect that by E11.5, mRNA of genes essential for chondrogenesis and extracellular matrix formation are upregulated in Wnt5a mutants. The expression profile supports the premature and delayed chondrogenesis observed in Wnt5a and Notum deficient tracheas, respectively. We conclude that Notum and Wnt5a are necessary for proper tracheal cartilage patterning by coordinating timely chondrogenesis. Thus, these studies shed light on molecular mechanisms underlying congenital anomalies of the trachea.
The Enhanced Activation of Innate Immunity inDrosophilaS2 Cells byMicrococcus luteusis Mediated by Relish
Authors: Kachaev Zaur M. , Ghassah Mona , Musabirov Anton A. , Shaposhnikov Alexander V. , Toropygin Ilya Y. , Polunina Yulia A. , Stepanov Nikita G. , Chmykhalo Victor K. , Shidlovskii Yulii V.
Published: September 2024

The IMD and Toll signaling pathways inDrosophila melanogastermediate the innate immune responses to Gram-negative and Gram-positive bacteria and fungi, respectively. Here we studied the involvement of the NF-κB transcription factor Relish, which is a mediator of the IMD pathway, in the humoral immune response to the Gram-positive bacteriaMicrococcus luteusandBacillus subtilisand the entomopathogenic fungusMetarhizium anisopliae, usingD. melanogasterS2 cells as a model. Activation of Relish proteolysis was observed after S2 cell treatment with the control Gram-negative bacteriumEscherichia coli. We found thatM. luteushad also a noticeable effect on Relish activation, whileB. subtilisandM. anisopliaeeffects were modest. Activation patterns of the genes encoding predominantly the IMD-pathway-dependent antimicrobial peptides (AMPs) and peptidoglycan recognition proteins (PGRPs), as well as the levels of Relish recruitment to the promoters of the genes, were found to be very similar in S2 cells treated withE. coliorM. luteusbut were lower and differed in the case ofB. subtilisandM. anisopliae.A Relish knockdown (KD) decreased the induction levels observed for all AMP and some PGRP genes in response toM. luteustreatment and the induction levels observed for several AMP genes afterM. anisopliaeandB. subtilisexposures. Therefore, our findings suggest that Relish plays a critical role in inducing the humoral immune response inDrosophilaS2 cells, contributing primarily to the response againstM. luteusand, to a lesser extent, to the responses againstB. subtilisandM. anisopliae.
DNA flexibility regulates transcription factor binding to nucleosomes
Authors: Mariani Luca , Liu Xiao , Lee Kwangwoon , Gisselbrecht Stephen S. , Cole Philip A. , Bulyk Martha L.
Published: September 2024

Cell fate decisions are controlled by sequence-specific transcription factors (TFs), referred to as ‘pioneer’ factors, that bind their target sites within nucleosomes (’pioneer binding’) and thus initiate chromatin opening. However, pioneers bind just a minority of their recognition sequences present in the genome, suggesting that local sequence context features may regulate pioneer binding. Here, we developed PIONEAR-seq, a highly parallel sequencing-based biochemical assay for high-throughput analysis of TF binding to nucleosomes on nucleosome positioning sequences. Using PIONEAR-seq, we characterized the pioneer binding of 7 human pioneer TFs. Comparison of TF binding to nucleosomes based on the synthetic Widom 601 (W601) model sequence versus three different genomic sequences revealed that the positional preferences of these TFs’ binding to nucleosomes (i.e., dyad, periodic and end binding) is determined by the broader sequence context of the nucleosome, rather than being a property intrinsic to the TF. We propose a model where the flexibility and rigidity within nucleosomal DNA regulate where pioneers bind within nucleosomes. Our results suggest that the broader physical properties of nucleosomal DNA represent another layer ofcis-regulatory information read out by TFs in eukaryotic genomes.
Agar concentration affects the evolution of antibiotic resistance and population genomics in experimental populationsPseudomonas aeruginosa
Authors: Akter Mahfuza , Bailey Susan F.
Published: September 2024

Bacteria live in a diversity of spatially structured environments, which can impact their evolutionary dynamics via local interactions and environmental variation. Spatial structure is expected to slow the rate of adaptive evolution, increase the amount of clonal competition and so increase diversity of evolutionary trajectories explored as a population evolves. In the lab, agar is a common way in which we add spatial structure to bacterial growth environments. In this study we explored the effects of agar concertation on experimental populations ofPseudomonas aeruginosaevolved in the presence/ absence of a sub-lethal concentration of an antibiotic, ciprofloxacin. We varied agar across four different concentrations which modified viscosity and so the rate at which bacteria move through their environment, as well as potentially shifting the mode of motility. We saw that increasing agar concentration decreased the rate of adaptation, and that the presence of antibiotics, amplified this effect. The number and frequency of evolved mutations also varied with agar concentration and the direction of the effect changed in the presence/ absence of antibiotics – for example, the number of high frequency mutation increased with agar concentration when antibiotics were absent but decreased when antibiotics were present. We also saw an increase in the degree of parallel evolution in populations evolved in the presence of antibiotics and even more so in higher concentrations of agar. Thus, we show that agar concentration, and so spatial structure, can be an important driver of evolutionary dynamics with important impacts on antibiotic resistance evolution including the rate and predictability of adaptation.
Benchmarking Protein Language Models for Protein Crystallization
Authors: Mall Raghvendra , Kaushik Rahul , Martinez Zachary A. , Thomson Matt , Castiglione Filippo
Published: September 2024

The problem of protein structure determination is usually solved by X-ray crystallography. Several in silico deep learning methods have been developed to overcome the high attrition rate, cost of experiments and extensive trial-and-error settings, for the predicting the crystallization propensities of proteins based on their sequences. In this work, we benchmark the power of open protein language models (PLMs) through the TRILL platform, a bespoke framework democratizing the usage of PLMs for the task of predicting crystallization propensities of proteins. By comparing LightGBM / XGBoost classifiers built on the embedding representations learned by different PLMs, such as ESM2, Ankh, ProtT5- XL, ProstT5, with the performance of state-of-the-art sequence-based methods like DeepCrystal, ATTCrys and CLPred, we identify the most effective methods for predicting crystallization outcomes. The LightGBM classifiers utilizing embeddings from ESM2 model with 30 and 36 transformer layers and 150 and 3,000 million parameters respectively have performance gains by 3 - 5% then all compared models for various evaluation metrics, including AUPR (Area Under Precision-Recall Curve), AUC (Area Under the Receiver Operating Characteristic Curve), and F1 score on independent test sets. Furthermore, we fine-tune the ProtGPT2 model available via TRILL to generate crystallizable proteins. Starting with 3, 000 generated proteins and through a step of filtration processes including consensus of all open PLM- based classifiers, sequence identity through CD-HIT, secondary structure compatibility, aggregation screening, homology search and foldability evaluation, we identified a set of 5 novel proteins as potentially crystallizable.
Directed disruption of IL2 aggregation sites produces designer biologics with enhanced specificity coupled to improved production capacity
Authors: Dashwood Amy , Makuyana Ntombizodwa , van der Kant Rob , Ghodsinia Arman , Hernandez Alvaro R. , Lienart Stephanie , Burton Oliver , Dooley James , Ali Magda , Kouser Lubna , Naranjo Francisco , Holt Matthew G. , Rousseau Frederic , Schymkowitz Joost , Liston Adrian
Published: September 2024

The pleotropic nature of interleukin-2 (IL2) has allowed it to be used as both a pro-inflammatory and anti-inflammatory therapeutic agent, through promotion of regulatory T cell (Treg) responses via the IL2RA receptor or promotion of CD8 T cell responses via the IL2RB receptor, respectively. However, the utility of IL2 as a treatment is limited by this same pleiotropy, and protein engineering to bias specificity towards either the regulatory T cell (Treg) or CD8 T cell lineage often requires a trade-off in protein production or total bioactivity. Here we use SolubiS, a computational algorithm-based method, to predict mutations within the IL2 structure to improve protein production yield while altering cellular selectivity, to generate a mutein with elevated therapeutic potential. The design and testing process identified the V126R (murine) / V111R (human) mutation as a Treg-enhancing mutein, creating a cation repulsion to inhibit primary binding to IL2RB, with a post-IL2RA confirmational shift enabling secondary IL2RB binding, and hence allowing the trimeric receptor complex to form. In human IL2, additional N110R T151R aggregation-protecting mutations could improve protein yield of the V111R mutation. The approach also generated novel CD8 T cell-promoting mutations. Y79K created a cation-cation repulsion with IL2RA, while Q50W enhanced CD8 T cell activity through potential π-stacking enhancing binding to IL2RB, with the combination highly stimulatory for CD8 T cells. For human IL2, Y65K (homolog to murine Y79K) coupled with E82K prevented IL2RA binding, however it required the aggregation-protecting mutations of N110R T151R to rescue production. These muteins, designed with both cellular specificity and protein production features, have potential as both biological tools and therapeutics.
Don’t bet against the odds! Odd prey in mixed species groups suffer fewer attacks than lone individuals
Authors: Shah Akanksha , Webster Mike M.
Published: September 2024

Mixed-species groups are common in nature. Such groups are characterised by the presence of one or more majority species, and smaller numbers of minority species. Minority individuals are expected to be subject to oddity effects; by looking or behaving differently to majority members they should be disproportionately targeted by predators. Given this, why might minority species remain in mixed-species groups? To address this question, we used threespine sticklebacks (Gasterosteus aculeatus) as predators and two ‘species’ of virtual prey presented via videos. We compared predator attacks on solitary prey, and odd and majority grouped prey individuals in groups of different sizes. We found that solitary prey were attacked significantly more than odd and majority grouped prey, while, in fact, odd and majority grouped prey did not differ from each other in terms of attacks received. We also found that prey in smaller groups suffered significantly more attacks than prey in larger groups. These findings provide no evidence for oddity effects but suggest evidence of a confusion effect. Natural mixed-species groups persist for various reasons, for example as foraging guilds, or because some members take advantage of more effective vigilance or alarm calls of others. We suggest, based on these findings, an additional non-mutually exclusive reason; under some circumstances, odd individuals might join larger heterospecific groups because any costs of being odd are greatly outweighed by the predation risk costs of remaining alone.
Spatial structure facilitates evolutionary rescue by drug resistance
Authors: Fruet Cecilia , Müller Ella Linxia , Loverdo Claude , Bitbol Anne-Florence
Published: September 2024

Bacterial populations often have complex spatial structures, which can impact their evolution. Here, we study how spatial structure affects the evolution of antibiotic resistance in a bacterial population. We consider a minimal model of spatially structured populations where all demes (i.e., subpopulations) are identical and connected to each other by identical migration rates. We show that spatial structure can facilitate the survival of a bacterial population to antibiotic treatment, starting from a sensitive inoculum. Specifically, the bacterial population can be rescued if antibiotic resistant mutants appear and are present when drug is added, and spatial structure can impact the fate of these mutants and the probability that they are present. Indeed, the probability of fixation of neutral or deleterious mutations providing drug resistance is increased in smaller populations. This promotes local fixation of resistant mutants in the structured population, which facilitates evolutionary rescue by drug resistance in the rare mutation regime. Once the population is rescued by resistance, migrations allow resistant mutants to spread in all demes. Our main result that spatial structure facilitates evolutionary rescue by antibiotic resistance extends to more complex spatial structures, and to the case where there are resistant mutants in the inoculum.

Author Summary

Antibiotic resistance is a major challenge, since bacteria tend to adapt to the drugs they are subjected to. Understanding what conditions facilitate or hinder the appearance and spread of resistance in a bacterial population is thus of strong interest. Most natural microbial populations have complex spatial structures. This includes host-associated microbiota, such as the gut microbiota. Here, we show that spatial structure can facilitate the survival of a bacterial population to antibiotic treatment, by promoting the presence of resistant bacteria. Indeed, neutral or deleterious mutants giving resistance can take over small populations more easily than large ones, thanks to the increased importance of fluctuations in small populations. Resistant mutants can then spread to the whole structured population. Thus, population spatial structure can be a source of antibiotic treatment failure. This effect of spatial structure is generic and does not require environment heterogeneity.
Spatial and temporal variation in farmland bird nesting ecology: Implications for effective Corn Bunting Emberiza calandra conservation
Authors: Anthes Nils , Staggenborg Julia , Handschuh Markus
Published: September 2024

Farmland bird populations continue to decline despite intense conservation efforts, possibly also because of incomplete knowledge on the drivers of local productivity. We therefore investigated spatial and temporal variation in nest site selection, breeding phenology, and nest survival for 225 nests of the Corn Bunting, a species of conservation concern in Central and Western Europe, in cropland-dominated, mixed, and grassland-dominated landscapes in SW Central Europe. Nesting phenology spread from April to August, started earlier at lower altitudes and progressed from grassland habitats to arable crops and eco-scheme flower fields. Most nests were placed in cultivated land, with substantial variation between landscape types but also between years within sites, so that large fractions of breeding attempts are prone to fail through land use operations in particular years. When nests were individually protected from land use, 'apparent' and 'Mayfield' survival rates differed substantially between nest habitats, with lowest survival in 2nd year flower fields and highest survival in fallow grassland. Accounting for land use survival from patch-specific mowing, harvesting, and grazing dates, 'total Mayfield nest survival' estimates dropped by about half to 21 %, 13 %, and 20 % for (hay) meadows, alfalfa / clover-grass leys, and pastures, respectively, which held about 2/3 of nests in mixed landscapes. To enhance productivity beyond the thresholds required for local population persistence, we propose refined conservation schemes that improve survival within production farmland, best coupled with the development of prolific 'Corn Bunting Landscapes'.
Phosphatase-independent suppression of mucosal inflammation and disease progression bySalmonellaSopB
Authors: Diab Nour , Stange Eva-Lena , Yong Chiun Huei , Deiwick Jörg , Vucur Mihael , Lüdde Tom , Hensel Michael , Torow Natalia , Zhang Kaiyi , Hornef Mathias W.
Published: September 2024

Salmonella entericasubsp.entericaserovar Typhimurium (S.Typhimurium) translocates effector molecules via itsSalmonellapathogenicity island (SPI)1 encoded type 3 secretion system (T3SS) to induce internalization by intestinal epithelial cells and manipulate cellular responses. Among these effector molecules, theSalmonellaouter protein B (SopB) was shown to possess phosphatidyl-inositol phosphatase activity and induce bacterial internalisation, promote cell survival, influence endosomal trafficking and alter host cell signalling. Using a neonatalS.Typhimurium infection model, we here show that SopBin vivosuppresses early epithelial chemokine expression, delays mucosal immune cell recruitment, reduces barrier impairment by enterocyte necroptosis, and prevents disease progression and premature death. Unexpectedly, this immunosuppressive effect was independent of the phosphatidyl-inositol phosphatase and phosphotransferase activity of SopB but required an intact N-terminal domain. Thus, SopB exerts a potent phosphatase-independent immunosuppressive effect to delay local tissue inflammation and disease progression likely to promote host transmission.
Are you talking to me? How the choice of speech register impacts listeners’ hierarchical encoding of speech
Authors: Piazza Giorgio , Carta Sara , Ip Emily , Pérez-Navarro Jose , Kalashnikova Marina , Martin Clara D. , Di Liberto Giovanni M.
Published: September 2024

Speakers accommodate their speech to meet the needs of their listeners, producing different speech registers. One such register is Foreigner-Directed Speech (FDS), which is the way native speakers address non-native listeners, typically characterized by features such as slow speech rate and phonetic exaggeration. Here, we investigated how register impacts the cortical encoding of speech at different levels of language integration. Specifically, we tested the hypothesis that enhanced comprehension of FDS compared with Native-Directed Speech (NDS) involves more than just a slower speech rate, influencing speech processing from acoustic to semantic levels. Electroencephalography (EEG) signals were recorded from Spanish native listeners, who were learning English (L2 learners), and English native listeners (L1 listeners) as they were presented with audio-stories. Speech was presented in English in three different speech registers: FDS, NDS and a control register (Slow-NDS) which is slowed down version of NDS. We measured the cortical tracking of acoustic, phonological, and semantic information with a multivariate temporal response function analysis (TRF) on the EEG signals. We found that FDS promoted L2 learners’ cortical encoding at all the levels of speech and language processing considered. First, FDS led to a more pronounced encoding of the speech envelope. Second, phonological encoding was more refined when listening to FDS, with phoneme perception getting closer to that of L1 listeners. Finally, FDS also enhanced the TRF- N400, a neural signature of lexical expectations. Conversely FDS impacted acoustic but not linguistic speech encoding in L1 listeners. Taken together, these results support our hypothesis that FDS accommodates speech processing in L2 listeners beyond what can be achieved by simply speaking slowly, impacting the cortical encoding of sound and language at different abstraction levels. In turn, this study provides objective metrics that are sensitive to the impact of register on the hierarchical encoding of speech, which could be extended to other registers and cohorts.
SAM-based Automatic Workflow for Histology Cyst Segmentation in Autosomal Dominant Polycystic Kidney Disease
Authors: Delgado-Rodriguez Pablo , Kinakh Roman , Aldabe Rafael , Munoz-Barrutia Arrate
Published: September 2024

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development of numerous cysts in the kidneys, ultimately leading to significant structural alterations and renal failure. Detailed investigations of this disease frequently utilize histological analyses of kidney sections across various stages of ADPKD progression. In this paper, we introduce an automated workflow leveraging the Segment Anything Model (SAM) neural network, complemented by a series of post-processing steps, to autonomously segment cysts in histological images. This approach eliminates the need for manual annotations or preliminary training phases and enables precise quantification of cystic changes over entire kidney sections. Application of this method to sequential histology images across the development timeline of ADPKD in mice demonstrated a notable increase in the proportion of diseased tissue from 8 to 12 weeks and from 12 to 16 weeks, with the cysts appearing progressively lighter. Our workflow not only surpasses the performance of the existing Cystanalyser tool but also offers enhanced flexibility and accuracy in full-image segmentation. The developed workflow is made publicly accessible to facilitate its adoption as an efficient tool for rapid and reliable cyst segmentation in histological studies.
Is criticality a unified set-point of brain function?
Authors: Hengen Keith B. , Shew Woodrow L.
Published: September 2024

Brains face selective pressure to optimize computation, broadly defined. This optimization is achieved by myriad mechanisms and processes that influence the brain’s computational state. These include development, plasticity, homeostasis, and more. Despite enormous variability over time and between individuals, do these diverse mechanisms converge on the same set-point? Is there a universal computational optimum around which the healthy brain tunes itself? The criticality hypothesis posits such a unified computational set-point. Criticality is a special dynamical brain state, defined by internally-generated multi-scale, marginally-stable dynamics which maximize many features of information processing. The first experimental support for this hypothesis emerged two decades ago, and evidence has accumulated at an accelerating pace, despite a contentious history. Here, we lay out the logic of criticality as a general computational end-point and systematically review experimental evidence for the hypothesis. We perform a meta-analysis of 143 datasets from manuscripts published between 2003 and 2024. To our surprise, we find that a long-standing controversy in the field is the product of a simple methodological choice that has no bearing on underlying dynamics. Our results suggest that a new generation of research can leverage the concept of criticality—as a unifying principle of brain function–to accelerate our understanding of behavior, cognition, and disease.
Life stage- and sex-specific sensitivity to nutritional stress in a holometabolous insect
Authors: Brueggemann Leon , Singh Pragya , Müller Caroline
Published: September 2024

Over the course of their lives, organisms can be repeatedly exposed to stress, which shapes their phenotype. At certain life stages, known as sensitive phases, individuals might be more receptive to such stress than at others. One of these stresses is nutritional stress, such as food limitation. However, little is known about how plastic responses differ between individuals experiencing nutritional stress early versus later in life or repeatedly, particularly in species with distinct ontogenetic niches. Moreover, there may be sex-specific differences due to distinct physiology.

The turnip sawfly,Athalia rosae (Hymenoptera: Tenthredinidae), is a holometabolous herbivore, whose larvae consume leaves and flowers, while the adults take up nectar. We examined the effects of starvation experienced at different life stages on life-history traits as well as adult behavioural and metabolic traits to determine which life-stage may be more sensitive to nutritional stress and how specific these traits respond. We exposed individuals to four distinct nutritional regimes, no, larval, or adult starvation, or starvation periods during both larval and adult stage.

Larvae exposed to starvation had a prolonged developmental time, and starved females reached a lower initial adult body mass than non-starved individuals. However, males did not differ in initial adult body mass regardless of larval starvation, suggesting the ability to conform well to poor nutritional conditions, possibly through changes in development and metabolism.

Adult behaviour, measured as activity, was not significantly impacted by larval or adult starvation in either sex. Individuals starved as larvae had similar carbohydrate and lipid (i.e. fatty acid) contents as non-starved individuals, potentially due to building up energy reserves during their prolonged development, while starvation during adulthood or at both stages led to reduced energy reserves in males.

This study indicates that the sensitivity of a life stage to nutritional stress depends on the specific trait under consideration. Life-history traits were mainly affected by larval nutritional stress, while activity appeared to be more robust and metabolism mostly impacted by the adult nutritional conditions. Individuals differed in their ability to conform to the given environment, with the responses being life stage- and sex-specific.
CIZ1 regulates G1 length and the CDK threshold for initiation of DNA replication to prevent DNA replication stress
Authors: Tollitt James , Briggs Tiernan , Allinson Sarah L. , Staples Christopher J. , Parsons Jason L. , Mort Richard L. , Copeland Nikki A.
Published: September 2024

Eukaryotic cell division is regulated by oscillating CDK activity, which must reach critical CDK threshold activity levels to progress through cell cycle stages. In low mitogen, low CDK environments cells exit the cell cycle into a non-proliferative quiescent state, G0, that plays essential roles in stem cell maintenance and cellular homeostasis. CIZ1 regulates cell cycle and epigenetic programmes, and CIZ1 ablation enhances genomic instability after release from quiescence. Here, we determined the mechanisms that promote genome instability in CIZ1 ablated cells using a combination of Fucci(CA) live cell imaging, cell-free DNA replication assays and DNA combing. Cell cycle dynamics are unaffected inCIZ1−/−(CIZ1 KO) fibroblasts; however, a specific post-quiescent phenotype is observed resulting in a reduced G1 phase and cell cycle length. The reduction in G1 length in CIZ1 KO cells is associated with increased cyclin E1/E2 and A2 expression, and enhanced phosphorylation of Rb leading to early restriction point bypass.CIZ1−/−cells are deficient in cyclin A chromatin binding and required increased cyclin-CDK activity for the initiation of DNA replication, which is associated with DNA replication stressin vitroandin vivo. Significantly, the CDK threshold for initiation of DNA replication was 2-fold higher in CIZ1 KO nuclei than parental controls. Importantly, addition of recombinant CIZ1in vitroandin vivopromotes recruitment of cyclin A to chromatin and reinstates the CDK threshold for initiation of DNA replication, reversing DNA replication stress and increasing replication fork rates. Loss of CIZ1 is associated with dysregulated cyclin-CDK signalling, resulting in reduced G1 length, an increased CDK activity threshold required to promote initiation of DNA replication that results in DNA replication stress. These data suggest that CIZ1 facilitates recruitment of cyclin-CDK complexes to chromatin and contributes to the mechanisms that determine the threshold CDK activity required for the G1/S transition in post-quiescent cells. Taken together the data support a role for CIZ1 in the prevention of DNA replication stress and maintenance of genome stability.
Early brain neuroinflammatory and metabolic changes identified by dual tracer microPET imaging in mice with acute liver injury
Authors: Palandira Santhoshi P. , Falvey Aidan , Carrion Joseph , Zeng Qiong , Chaudhry Saher , Grossman Kira , Turecki Lauren , Nguyen Nha , Brines Michael , Chavan Sangeeta S. , Metz Christine N. , Al-Abed Yousef , Chang Eric H. , Ma Yilong , Eidelberg David , Vo An , Tracey Kevin J. , Pavlov Valentin A.
Published: September 2024

Background

Acute liver injury (ALI) that progresses into acute liver failure (ALF) is a life-threatening condition with an increasing incidence and associated costs. Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosing is among the leading causes of ALI and ALF in the Northern Hemisphere. Brain dysfunction defined ashepatic encephalopathyis one of the main diagnostic criteria for ALF. While neuroinflammation and brain metabolic alterations significantly contribute to hepatic encephalopathy, their evaluation at early stages of ALI remained challenging. To provide insights, we utilized post-mortem analysis and non-invasive brain micro positron emission tomography (microPET) imaging of mice with APAP-induced ALI.

Methods

Male C57BL/6 mice were treated with vehicle or APAP (600 mg/kg, i.p.). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver damage (using H&E staining), hepatic and serum IL-6 levels, and hippocampal IBA1 (using immunolabeling) were evaluated at 24h and 48h. Vehicle and APAP treated animals also underwent microPET imaging utilizing a dual tracer approach, including [11C]-peripheral benzodiazepine receptor ([11C]PBR28) to assess microglia/astrocyte activation and [18F]-fluoro-2-deoxy-2-D-glucose ([18F]FDG) to assess energy metabolism. Brain images were pre-processed and evaluated using conjunction and individual tracer uptake analysis.

Results

APAP-induced ALI and hepatic and systemic inflammation were detected at 24h and 48h by significantly elevated serum ALT and AST levels, hepatocellular damage, and increased hepatic and serum IL-6 levels. In parallel, increased microglial numbers, indicative for neuroinflammation were observed in the hippocampus of APAP-treated mice. MicroPET imaging revealed overlapping increases in [11C]PBR28 and [18F]FDG uptake in the hippocampus, thalamus, and habenular nucleus indicating microglial/astroglial activation and increased energy metabolism in APAP-treated mice (vs. vehicle-treated mice) at 24h. Similar significant increases were also found in the hypothalamus, thalamus, and cerebellum at 48h. The individual tracer uptake analyses (APAP vs vehicle) at 24h and 48h confirmed increases in these brain areas and indicated additional tracer- and region-specific effects including hippocampal alterations.

Conclusion

Peripheral manifestations of APAP-induced ALI in mice are associated with brain neuroinflammatory and metabolic alterations at relatively early stages of disease progression, which can be non-invasively evaluated using microPET imaging and conjunction analysis. These findings support further PET-based investigations of brain function in ALI/ALF that may inform timely therapeutic interventions.