bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-related spatial ecology of Audouin’s gull during the non-breeding season
Authors: Ponti Raquel , Morera-Pujol Virginia , Sallent Ángel , González-Solís Jacob , Ramos Raül 
Published: October 2023

AbstractRelationships between individual’s age and the movement ecology and habitat preference of long-lived migratory birds still remain understudied. According to the exploration-refinement hypothesis it is thought that adults would select better and more productive areas for foraging than inexperienced juvenile birds would do. Additionally, age-related differences in migratory patterns and exploited habitats could be explained by the attempt to avoid competition between juveniles and adults. Here, we explored the differences in the migratory patterns, habitat selection and foraging behaviour between juvenile and adult Audouin’s gulls (Ichthyaetus audouinii), a species listed as vulnerable by the IUCN. We captured 9 juveniles and 8 adults in the colony of San Pedro (SE Spain) and equipped them with high-resolution 5-min programmed GPS to track their postnuptial/first migration and non-breeding destinations. First, juveniles tended to migrate longer distances than adults did. Second, the time spent foraging between age groups did not differ. Third, freshwater masses constituted an essential habitat during the non-breeding season for both juveniles and adults. Fourth, we found that adults used a greater variety of habitats than juveniles did, but adults positively select foraging habitats despite the low availability while juveniles do not. Finally, repeatability in habitat use of individuals of the same age was rather low. We provided evidence of age-related differences in migratory patterns and habitat exploitation during the non-breeding period in a migratory seabird which can be explained by the avoidance of competition between adults and juveniles and the greater experience in foraging performance that adults have in comparison with juveniles.
ENDOTHELIAL GENE REGULATORY ELEMENTS ASSOCIATED WITH CARDIOPHARYNGEAL LINEAGE DIFFERENTIATION
Authors: Aurigemma Ilaria , Lanzetta Olga , Cirino Andrea , Allegretti Sara , Lania Gabriella , Ferrentino Rosa , Krishnan Varsha Poondi , Angelini Claudia , Illingworth Elizabeth , Baldini Antonio 
Published: October 2023

ABSTRACTEndothelial cells (EC) differentiate from multiple sources, including the cardiopharyngeal mesoderm, which gives rise also to cardiac and branchiomeric muscles. Here, we used a cardiogenic mesoderm cell differentiation model that also activates an endothelial transcription program to identify endothelial regulatory elements activated in early cardiogenic mesoderm. Integrating our chromatin remodeling and gene expression data with available single-cell RNA-seq data from mouse embryos, we identified 101 putative regulatory elements of EC genes. We then applied a machine-learning strategy, trained on validated enhancers, to predict the probability of the sequences to function as enhancers. The computational assay determined that 50% of these sequences were likely enhancers, some of which have been previously reported. We also identified a smaller set of regulatory elements of well-known EC genes and validated them using genetic and epigenetic perturbation. Finally, we used the integration of multiple data sources and computational tools to search for transcriptional factor binding motifs. In conclusion, we identified novel EC regulatory sequences with a high likelihood to be enhancers, and we validated a subset of them using computational and cell culture models. Motif analyses revealed that the core EC transcription factors GATA/ETS/FOS is a likely driver of EC differentiation in cardiopharyngeal mesoderm.
High capacity of BrazilianAedes aegyptipopulations to transmit a locally circulating lineage of Chikungunya virus
Authors: de Freitas Amanda Cupertino , Rezende Fernanda Oliveira , de Mendonça Silvana Faria , Baldon Lívia Vieira , Silva Emanuele Guimarães , Ferreira Flávia Viana , de Almeida João Paulo , Amadou Siad Cedric , Marçal Bruno Almeida , Comini Sara Grangeiro , Rocha Marcele Neves , Fritsch Hegger Machado , Giovanetti Marta , Alcantara Luiz Carlos , Moreira Luciano Andrade , Ferreira Alvaro Gil 
Published: October 2023

AbstractThe global incidence of chikungunya has surged in recent decades, with South America, particularly Brazil, experiencing devastating outbreaks. The primary vector for transmitting CHIKV in urban areas is the mosquito speciesAedes aegypti, which is very abundant in Brazil. However, little is known about the impact of locally circulating CHIKV genotypes and specific combinations of mosquito populations on vector competence. In this study, we analyzed and compared the infectivity and transmissibility of a recently isolated CHIKV-ECSA lineage from Brazil among fourAe. aegyptipopulations collected from different regions of the country. When exposed to CHIKV-infected mice for blood feeding, all mosquito populations showed high infection rates and dissemination efficiency. Moreover, using a mouse model to assess transmission rates in a manner that better mirrors natural cycles, we observed that these populations exhibit highly efficient transmission rates of CHIKV-ECSA. Our findings underscore the robust capability of BrazilianAe. aegyptipopulations to transmit the locally circulating CHIKV-ECSA lineage, potentially explaining its higher prevalence compared to the Asian lineage also introduced in Brazil.Author SummaryChikungunya virus (CHIKV) is an alphavirus transmitted by mosquitoes, gaining attention due to its rapid global spread and public health impact. Initially isolated in Tanzania in 1952, it was confined to Africa, Asia, and the Indian subcontinent. Local transmission of CHIKV in the Americas began in December 2013, leading to a 2014 epidemic. TheAedes aegyptimosquito, prevalent in Brazil, is suspected as the primary vector. Yet, our understanding of how different mosquito populations and virus lineages impact spread is limited. In this Brazilian study, we collected mosquitoes from four regions, exposing them to the local African ECSA lineage of CHIKV. Remarkably, all mosquito populations exhibited high infection rates and efficient virus transmission to vertebrate hosts. This research sheds light on why the ECSA chikungunya lineage is spreading rapidly in Brazil. The BrazilianAe. aegyptimosquitoes appear to possess exceptional capabilities in transmitting African ECSA lineage of CHIKV, potentially contributing to its rapid dissemination within the country and neighboring regions. Comprehending these dynamics is vital for developing strategies to control and mitigate the impact of chikungunya in affected areas.
Infection dynamics in the urinary tract - The importance of non-planktonic phases during early infection and resistance evolution
Authors: Raatz Michael , Drabik Karolina , de Azevedo-Lopes Amanda , Traulsen Arne , Wacław Bartłomiej 
Published: October 2023

Treatment of urinary tract infections (UTIs) and the prevention of their recurrence is a pressing global health problem. During the infection establishment, pathogenic bacteria may attach to and invade into the bladder tissue, and thus access non-planktonic phases besides the bladder lumen. Planktonic, attached, and intracellular bacteria face different selection pressures from physiological responses (frequent micturition and immune responses), or antibiotic treatment. Acknowledging this heterogeneity of selection pressures is essential to increase treatment efficacy, reduce resistance evolution and develop new treatments. Here, we present a mathematical model capturing the initial infection phase to unravel the effects of this heterogeneity on the ecological and evolutionary dynamics of UTIs. We explicitly represent planktonic bacteria in the bladder lumen, bacteria attached to epithelial cells of the bladder wall, and bacteria that have invaded these epithelial cells. We find that access to non-planktonic compartments increases the risk of infection establishment substantially. With antibiotic treatment, the trajectories of resistance evolution are shaped by the accessibility of the intracellular compartment and antibiotic permeation into the epithelial cells. Further, we evaluate conditions where probiotic pretreatment can reduce the pathogen load during an infection and increase the efficacy of accompanying antibiotic therapies. We find that faster-growing probiotic strains achieve a stronger increase in antibiotic treatment efficacy, although too strong antibiotic treatment can diminish this effect. Our study shows that accounting for the selection heterogeneity is crucial to understand the eco-evolutionary dynamics of UTIs, and that mathematical modeling can help to steer this complex system into a healthy state.Competing InterestsThe authors declare no competing interests.
Reduction of a-synuclein aggregates by PIKfyve inhibition via TFEB-mediated lysosomal biogenesis in a Parkinson disease model
Authors: Lucas-Del-Pozo Sara , Uras Giuseppe , Fierli Federico , Lentini Veronica , Koletsi Sofia , Chau Kai-Yin , Hughes Derralynn , Schapira Anthony HV 
Published: October 2023

AbstractParkinson disease is a neurodegenerative disorder characterised by impairment of motor function, and is associated with a progressive accumulation of insoluble aggregates of misfolded alpha-synuclein. In the present study, we exploited the SH-SY5Y cell model overexpressing a pro-aggregation form of alpha-synuclein to investigate the efficacy of PIKfyve-mediated lysosomal biogenesis, through TFEB, as potential target for Parkinson therapy.To investigate this, we exploited high-content imaging along with enzymatic assays to follow the progression of lysosomal biogenesis, lysosomal function and alpha-synuclein accumulation. The cellular model exploited in this study recapitulated important elements of the biochemical phenotype observed in Parkinson patient-derived neurons, including synuclein aggregates and impaired glucocerebrosidase (GCase) function. PIKfyve inhibition by YM201636 resulted in a lysosomal-dependant reduction of alpha-synuclein aggregates as early as 24 hours post-treatment. The mechanism of action of YM201636 was shown to be TFEB-mediated, with an increase in TFEB in the nuclei which subsequently resulted in increased lysosomal markers LAMP1 and GCase. PIKfyve inhibtion efficacy was also tested in differentiated SH-SY5Y cells, exhibiting a neuron-like morphology. In these cells, YM201636 also significantly reduced alpha-synuclein aggregates and increased TFEB nuclear presence.These findings suggest that PIKfyve inhibition could be exploited as therapeutic target for Parkinson disease.
Neurocognitive Dynamics of Preparatory and Adaptive Cognitive Control: Insights from Mass-Univariate and Multivariate Pattern Analysis of EEG data
Authors: García Alanis José C. , Güth Malte R. , Chavanon Mira-Lynn , Peper Martin 
Published: October 2023

AbstractCognitive control encompasses a set of basic perceptual and reasoning processes that help us align thoughts and actions with goals. While a growing body of research indicates that these processes can be independently engaged and tuned to fit different tasks (e.g., behavioural preparation vs behavioural adaptation), the dynamic interplay of these processes and their functional timing within the information stream, remains elusive. In this study, we used a combination of mass-univariate and multivariate pattern analysis to examine electroencephalography data from 52 participants, recorded during performance of the Dot Pattern Expectancy Task (DPX), a task designed to assess both preparatory and adaptive cognitive control. Contrary to the notion of isolated neural signatures for either cognitive control mode, our data indicates that cognitive control engages a sequence of distinct yet partially overlapping brain activation patterns. Preparatory cue-stimuli evoked early transient occipital-parietal amplitude responses that were followed by enhanced sustained central-parietal and fronto-central amplitude responses. Similarly, adaptive probe-stimuli evoked enhanced early transient occipital-parietal amplitude responses, but these were followed by enhanced transient, fronto-central and central parietal amplitude responses. Moreover, we found significant relationships between the magnitude of the central-parietal and fronto-central amplitude response pattern and behavioural performance in the DPX. This research not only extends prior work but also offers valuable insights into the functional timing and organisation of the neurocognitive processes underpinning both preparatory and adaptive cognitive control.
Using an ODE model to separate Rest and Task signals in fMRI
Authors: Kashyap Amrit , Geenjaar Eloy , Bey Patrik , Dhindsa Kiret , Glomb Katharina , Plis Sergey , Keilholz Shella , Ritter Petra 
Published: October 2023

AbstractCortical activity results from the interplay between network-connected regions that integrate information and stimulus-driven processes originating from sensory motor networks responding to specific tasks. Separating the information due to each of these components has been challenging, and the relationship as measured by fMRI in each of these cases Rest (network) and Task (stimulus driven) remains a significant outstanding question in the study of large-scale brain dynamics. In this study, we developed a network ordinary differential equation (ODE) model using advanced system identification tools to analyze fMRI data from both rest and task conditions. We demonstrate that task-specific ODEs are essentially a subset of rest-specific ODEs across four different tasks from the Human Connectome Project. By assuming that task activity is a relative complement of rest activity, our model significantly improves predictions of reaction times on a trial-by-trial basis, leading to a 9%increase in explanatory power (R2) across all 14 tested subtasks. Our findings establish the principle of the Active Cortex Model, which posits that the cortex is always active and that Rest State encompasses all processes, while certain subsets of processes get elevated to perform specific task computations. This study offers a crucial perspective on the nature of large-scale brain dynamics and introduces one of the first models to causally link large-scale brain activity, equations representing these dynamics, and behavioral variables within a single framework.
Neuroimaging genomics as a window into the evolution of human sulcal organization
Authors: Goltermann Ole , Alagöz Gökberk , Molz Barbara , Fisher Simon E. 
Published: October 2023

AbstractPrimate brain evolution has involved prominent expansions of the cerebral cortex, with largest effects observed in the human lineage. Such expansions were accompanied by fine-grained anatomical alterations, including increased cortical folding. However, the molecular bases of evolutionary alterations in human sulcal organisation are not yet well understood. Here, we integrated data from recently completed large-scale neuroimaging genetic analyses with annotations of the human genome relevant to various periods and events in our evolutionary history. These analyses identified single-nucleotide polymorphism (SNP) heritability enrichments in foetal brain human-gained enhancer elements for a number of sulcal structures, including the central sulcus, which is implicated in human hand dexterity. We zeroed-in on a genomic region which harbours DNA variants associated with left central sulcus shape, a human-gained enhancer element, and genetic loci involved in neurogenesis includingZIC4, to illustrate the value of this approach for probing the complex factors contributing to human sulcal evolution.
Soil fungi remain active and invest in storage compounds during drought independent of future climate conditions
Authors: Canarini Alberto , Fuchslueger Lucia , Schnecker Jörg , Metze Dennis , Nelson Daniel B. , Kahmen Ansgar , Watzka Margarete , Pötsch Erich M. , Schaumberger Andreas , Bahn Michael , Richter Andreas 
Published: October 2023

AbstractMicrobial growth is central to soil carbon cycling. However, how microbial communities grow under climate change is still largely unexplored. In an experiment simulating future climate conditions (increased atmospheric CO2and temperature) and drought, we traced2H or18O applied via water-vapor exchange into fatty acids or DNA, respectively, allowing to measure community- and group-level adjustments in soil microbial physiology (replication, storage product synthesis, and carbon use efficiency, CUE). We show, that while overall community-level growth decreased by half during drought, fungal growth remained stable demonstrating an astonishing resistance of fungal activity against soil moisture changes. In addition, fungal investment into storage triglycerides increased more than five-fold under drought. CUE (the balance between anabolism and catabolism) was unaffected by drought but decreased in future climate conditions. Our results highlight that accounting for different growth strategies can foster our understanding of soil microbial contribution to C cycling and feedback to climate change.
Neural signatures of stress susceptibility and resilience in the amygdala-hippocampal network
Authors: Xia Frances , Fascianelli Valeria , Vishwakarma Nina , Ghinger Frances Grace , Fusi Stefano , Kheirbek Mazen A 
Published: October 2023

AbstractThe neural dynamics that underlie divergent anhedonic responses to stress remain unclear. Here, we identified neuronal dynamics in an amygdala-hippocampal circuit that distinguish stress resilience and susceptibility. In a reward-choice task, basolateral amygdala (BLA) activity in resilient mice showed enhanced discrimination of upcoming reward choices. In contrast, a rumination-like signature emerged in the BLA of susceptible mice; a linear decoder could classify the intention to switch or stay on a previously chosen reward. Spontaneous activity in the BLA of susceptible mice was higher dimensional than controls, reflecting the exploration of a larger number of distinct neural states. Manipulation of vCA1-BLA inputs rescued dysfunctional neural dynamics and anhedonia in susceptible mice, suggesting that targeting this pathway can enhance BLA circuit function and ameliorate of depression-related behaviors.One-Sentence SummaryIdentification and rescue of dysfunctional vCA1-BLA population dynamics and behavior in stress-susceptible mice.
Learning gene networks under SNP perturbation using SNP and allele-specific expression data
Authors: Yoon Jun Ho , Kim Seyoung 
Published: October 2023

AbstractAllele-specific expression quantification from RNA-seq reads provides opportunities to study the control of gene regulatory networks bycis-acting andtrans-acting genetic variants. Many existing methods performed a single-gene and single-SNP association analysis to identify expression quantitative trait loci (eQTLs), and placed the eQTLs against known gene networks for functional interpretation. Instead, we view eQTL data as a capture of the effects of perturbation of gene regulatory system by a large number of genetic variants and reconstruct a gene network perturbed by eQTLs. We introduce a statistical framework called CiTruss for simultaneously learning a gene network andcis-acting andtrans-acting eQTLs that perturb this network, given population allele-specific expression and SNP data. CiTruss uses a multi-level conditional Gaussian graphical model to modeltrans-acting eQTLs perturbing the expression of both alleles in gene network at the top level andcis-acting eQTLs perturbing the expression of each allele at the bottom level. We derive a transformation of this model that allows efficient learning for large-scale human data. Our analysis of the GTEx and LG×SM advanced intercross line mouse data for multiple tissue types with CiTruss provides new insights into genetics of gene regulation. CiTruss revealed that gene networks consist of local subnetworks over proximally located genes and global subnetworks over genes scattered across genome, and that several aspects of gene regulation by eQTLs such as the impact of genetic diversity, pleiotropy, tissue-specific gene regulation, and local and long-range linkage disequilibrium among eQTLs can be explained through these local and global subnetworks.
CRISPR screens and lectin microarrays identify novel high mannose N-glycan regulators
Authors: Tsui C Kimberly , Twells Nicholas , Doan Emma , Woo Jacqueline , Khosrojerdi Noosha , Brooks Janiya , Kulepa Ayodeji , Webster Brant , Mahal Lara K , Dillin Andrew 
Published: October 2023

AbstractGlycans play critical roles in cellular signaling and function. Unlike proteins, glycan structures are not templated from genes but the concerted activity of many genes, making them historically challenging to study. Here, we present a strategy that utilizes pooled CRISPR screens and lectin microarrays to uncover and characterize regulators of cell surface glycosylation. We applied this approach to study the regulation of high mannose glycans – the starting structure of all asparagine(N)-linked-glycans. We used CRISPR screens to uncover the expanded network of genes controlling high mannose surface levels, followed by lectin microarrays to fully measure the complex effect of select regulators on glycosylation globally. Through this, we elucidated how two novel high mannose regulators – TM9SF3 and the CCC complex – control complex N-glycosylation via regulating Golgi morphology and function. Notably, this method allowed us to interrogate Golgi function in-depth and reveal that similar disruption to Golgi morphology can lead to drastically different glycosylation outcomes. Collectively, this work demonstrates a generalizable approach for systematically dissecting the regulatory network underlying glycosylation.
Vaccination by single dose sporozoite injection of blood stage attenuated malaria parasites
Authors: Sattler Julia M. , Keiber Lukas , Abdelrahim Aiman , Zheng Xinyu , Jäcklin Martin , Zechel Luisa , Moreau Catherine A. , Fischer Manuel , Janse Chris J. , Hoffmann Angelika , Hentzschel Franziska , Frischknecht Friedrich 
Published: October 2023

AbstractAn efficient malaria vaccine remains elusive. As an alternative to malaria subunit vaccines, vaccination approaches are currently explored using livePlasmodiumparasites, either attenuated mosquito-derived sporozoites or attenuated blood stage parasites. Both approaches would profit from the availability of attenuated and avirulent parasites with a reduced blood stage multiplication rate. Ideally, such slow growing parasites would proceed normally through the mosquito but cause a self-limiting infection upon transmission. Here we screened gene-deletion mutants of the rodent parasiteP. bergheiand the human parasiteP. falciparumfor slow growth. In addition, we tested theP. bergheimutants for avirulence in mice and self-resolving blood stage infections, while preserving sporozoite formation and liver infection. Targeting fifty genes yielded seventeenP. bergheigene-deletion mutants with two mutants causing self-clearing infections in mice while retaining full transmissibility through mosquitoes. For those, infection of mice by a low number of blood stages, infected-mosquito bites or by single injection of sporozoites led to protection from disease after challenge with wild type sporozoites. Two of six generatedP. falciparumgene-deletion mutants showed a slow growth rate. Slow growing, avirulentP. falciparummutants will constitute valuable tools to inform on the induction of immune responses and aid in developing new as well as safeguarding existing attenuated parasite vaccines.