bluuebunny/crossref_metadata_2025_split huggingface dataset:
FERMO: a Dashboard for Streamlined Rationalized Prioritization of Molecular Features from Mass Spectrometry Data
Authors: Zdouc Mitja M. , Bayona Maldonado Lina M. , Augustijn Hannah E. , Soldatou Sylvia , de Jonge Niek , Jaspars Marcel , van Wezel Gilles P. , Medema Marnix H. , van der Hooft Justin J. J. 
Published: December 2022

ABSTRACTSmall molecules can selectively modulate biological processes and thus generate phenotypic variation. Biological samples are complex matrices, and liquid chromatography tandem mass spectrometry often detects hundreds of molecules, of which only a fraction may be associated with this variation. The challenge therefore lies in the prioritization of the most relevant molecules for further investigation. Tools are needed to effectively contextualize mass spectrometric data with phenotypical and environmental (meta)data. To accelerate this task, we developed FERMO, a dashboard application combining mass spectrometry data with qualitative and quantitative biological observations. FERMO’s centralized interface enables users to rapidly inspect data, formulate hypotheses, and prioritize molecules of interest. We demonstrate the applicability of FERMO in a case study on antibiotic activity of bacterial extracts, where we successfully prioritized the bioactive molecule siomycin out of 143 molecular features. We expect that besides natural product discovery, FERMO will find application in a wide range of omics-driven fields.
LRRC37B is a species-specific regulator of voltage-gated channels and excitability in human cortical neurons
Authors: Libé-Philippot Baptiste , Lejeune Amélie , Wierda Keimpe , Vlaeminck Ine , Beckers Sofie , Gaspariunaite Vaiva , Bilheu Angéline , Nyitrai Hajnalka , Vennekens Kristel M. , Bird Thomas W. , Soto Daniela , Dennis Megan Y , Comoletti Davide , Theys Tom , de Wit Joris , Vanderhaeghen Pierre 
Published: December 2022

AbstractThe enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits, but the underlying molecular mechanisms remain largely unknown. Here we report that the hominid-specific geneLRRC37Bencodes a novel receptor expressed in a subset of human cortical pyramidal neurons (CPNs). LRRC37B protein localizes at the axon initial segment (AIS), the specialized domain triggering action potentials.LRRC37Bectopic expression in mouse CPNsin vivoleads to reduced intrinsic excitability, a distinctive feature of some classes of human CPNs. At the molecular level, LRRC37B acts as a receptor for the secreted ligand FGF13A and interacts with the voltage gated sodium channel (VGSC) beta subunit SCN1B, thereby inhibiting the channel function of VGSC, specifically at the AIS. Electrophysiological recordings in adult human cortical slices reveals that endogenous expression of LRRC37B in human CPNs reduces neuronal excitability.LRRC37Bthus acts as a species-specific modifier of human cortical neuron function, with important implications for human brain evolution and diseases.
TrAGEDy: Trajectory Alignment of Gene Expression Dynamics
Authors: Laidlaw Ross F. , Briggs Emma M. , Matthews Keith R. , McCulloch Richard , Otto Thomas D. 
Published: December 2022

1AbstractMotivationSingle-cell transcriptomics sequencing is used to compare different biological processes. However, often, those processes are asymmetric which are difficult to integrate. Current approaches often rely on integrating samples from each condition before either cluster-based comparisons or analysis of an inferred shared trajectory.ResultsWe present Trajectory Alignment of Gene Expression Dynamics (TrAGEDy), which allows the alignment of independent trajectories to avoid the need for error-prone integration steps. Across simulated datasets, TrAGEDy returns the correct underlying alignment of the datasets, outperforming current tools which fail to capture the complexity of asymmetric alignments. When applied to real datasets, TrAGEDy captures more biologically relevant genes and processes, which other differential expression methods fail to detect when looking at the developments of T cells and the bloodstream forms ofTrypanosoma bruceiwhen affected by genetic knockouts.Availability and ImplementationTrAGEDy is freely available athttps://github.com/No2Ross/TrAGEDy, and implemented in R.Contactthomasdan.otto@glasgow.ac.uk
Comprehensive profiling of polyclonal sera targeting a non-enveloped viral capsid
Authors: Álvarez-Rodríguez Beatriz , Buceta Javier , Geller Ron 
Published: December 2022

AbstractDespite their fundamental role in resolving viral infections, our understanding of how polyclonal neutralizing antibody responses target non-enveloped viruses remains limited. To define these responses, we obtained the full antigenic profile of multiple human and mouse polyclonal sera targeting the capsid of a prototypical picornavirus. Our results uncover significant variation in the breadth and strength of neutralization sites targeted by individual human polyclonal responses, which contrasted with homogenous responses observed in experimentally infected mice. We further use these comprehensive antigenic profiles to define key structural and evolutionary parameters that are predictive of escape, assess epitope dominance at the population level, and reveal a need for at least two mutations to achieve significant escape from multiple sera. Overall, our data provide the first comprehensive analysis of how polyclonal sera target a non-enveloped viral capsid and help define both immune dominance and escape at the population level.
Ecological assembly of natural soundscapes in the Garajonay National Park (Spain)
Authors: Ortiz-Álvarez Rüdiger , García-Puig Marta , Garate Leire 
Published: December 2022

AbstractNatural sound contains data about the ecology of animal populations, communities, and the full ecosystem, resulting from a complex evolution and varying according to the environment. Amongst the processes that are hypothesized to explain sound assemblages, or soundscapes, one is the acoustic niche hypothesis: sounds produced by species calling at the same time seek avoid overlapping, leading to an acoustic differentiation of signals. Soundscapes are more complex in the most pristine environments and show responses to habitat degradation and physical perturbations; hence here, we focus on La Gomera, in the Canary Islands (Spain). This island is the only location in Europe where primary cloud forests are well preserved and thrive on an island with varied orography, microclimates, disturbances, and vegetation types. In this article, we adapted a method to quantify the importance of acoustic niche partitioning and also the opposite process: acoustic aggregation. To do so, we explored soundscapes at different temporal scales in forests with variable degrees of perturbation and maturity. A secondary goal of this report is to compare how soundscapes could differ in an area affected by a wildfire, and undisturbed equivalents, in summer in winter, seasons with contrasting temperatures and wind regimes. We conclude that tracking faunal activity and behavior through soundscape monitoring could be a piece of useful complementary information to guide conservation decisions and future restoration efforts in the Garajonay National Park (La Gomera).Highlights○ The mature forest and the transitional forest are similar in terms of sound levels, frequencies, and dynamics, although the transitional forest had higher sound levels of the lower frequencies (higher NDSI).○ The mature forest has stronger and more active assembly mechanisms (i.e., acoustic aggregation and acoustic niche partitioning) and a higher acoustic diversity index (ADI) than the transitional forest. Assembly organizes differently in both locations.○ In both the mature and the transitional forests, we found an inverse relationship between the ADI and acoustic niche partitioning. At the highest diversities (more frequency bands occupied), the weakest is the temporal avoidance of calls with similar frequencies.○ The vulnerability of the burned location is highest during the harsh summer, but in winter, it hosts a community very similar to the intact vegetation in terms of ADI and sound levels.
Community Detection in Brain Connectome using Quantum Annealer Devices
Authors: Wierzbiński Marcin , Falcó-Roget Joan , Crimi Alessandro 
Published: December 2022

ABSTRACTRecent advancements in network neuroscience are pointing in the direction of considering the brain as a small-world system with segregated regions integrated to facilitate different cognitive tasks and functions. In this context, community detection is a pivotal issue in computational neuroscience. In this paper we explore community detection within brain connectomes using the power of quantum annealers, and in particular the Leap’s Hybrid Solver. Our results shows that quantum annealers can achieve higher modularity index compared to classical annealer while computing communities of brain connectomes. Those promising preliminary results points out that quantum annealers might be the better choice compared to classical computing optimization process.
A chromosome level genome assembly of longnose gar,Lepisosteus osseus
Authors: Mallik Rittika , Carlson Kara B. , Wcisel Dustin J. , Fisk Michael , Yoder Jeffrey A. , Dornburg Alex 
Published: December 2022

AbstractHolosteans (gars and bowfins) represent the sister lineage to teleost fishes, the latter being a clade that comprises over half of all living vertebrates and includes important models for comparative genomics and human health. A major distinction between the evolutionary history of teleosts and holosteans is that all teleosts experienced a genome duplication event in their early evolutionary history. As holostean genomes did not undergo a round of genome duplication, they have been heralded as a means to bridge teleost models to other vertebrate genomes. However, only three species of holosteans have been genome sequenced to date and sequencing of more species is needed to fill sequence sampling gaps and provide a broader comparative basis for understanding holostean genome evolution. Here we report the first high quality reference genome assembly and annotation of the longnose gar (Lepisosteus osseus). Our final assembly consists of 22,709 scaffolds with a total length of 945 bp with contig N50of 116.6 kb. Using BRAKER2, we annotated a total of 30,068 genes. Analysis of the repetitive regions of the genome reveals the genome to contain 29.1% transposable elements, and the longnose gar to be the only other known vertebrate outside of the spotted gar to contain CR1, L2, Rex1, and Babar. These results highlight the potential utility of holostean genomes for understanding the evolution of vertebrate repetitive elements and provide a critical reference for comparative genomic studies utilizing ray-finned fish models.SignificanceOver half of all living vertebrates are teleost fishes, including numerous experimental models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). However, translating research in teleost models to other organisms such as humans is often challenged by the fact that teleosts experienced a genome duplication event in their early evolutionary history. Recent genome sequencing of three holosteans, the sister lineage to teleosts that did not experience a genome duplication event, has revealed these taxa to be critical for linking homologs between teleosts and other vertebrates. Sequencing of holostean genomes remains limited, thereby impeding further comparative genomic studies. Here we fill this sampling gap through the genomic sequencing of the longnose gar (Lepisosteus osseus). This annotated reference genome will provide a useful resource for a range of comparative genomic applications that span fields as diverse as immunogenetics, developmental biology, and the understanding of regulatory sequence evolution.
7-Tesla evidence for columnar and rostral–caudal organization of the human periaqueductal gray response in the absence of threat: a working memory study
Authors: Fischbach Alexandra K. , Satpute Ajay B. , Quigley Karen S. , Kragel Philip A. , Chen Danlei , Bianciardi Marta , Wald Lawrence L. , Wager Tor D. , Choi Ji-Kyung , Zhang Jiahe , Barrett Lisa Feldman , Theriault Jordan E. 
Published: December 2022

AbstractThe periaqueductal gray (PAG) is a small midbrain structure that surrounds the cerebral aqueduct, regulates brain–body communication, and is often studied for its role in “fight-or-flight” and “freezing” responses to threat. We used ultra-high field 7-Tesla fMRI to resolve the PAG in humans and distinguish it from the cerebral aqueduct, examining itsin vivofunction in humans during a working memory task (N = 87). Relative to baseline fixation, both mild and moderate task-elicited cognitive demands elicited bilateral BOLD increases in ventrolateral PAG (vlPAG), a region previously observed to show increased activity during anticipated painful threat in both non-human and human animals. The present task posed only the most minimal (if any) “threat”. The mild-demand condition involved a task easier than remembering a phone number, elicited a heart rate decrease relative to baseline, yet nonetheless elicited a bilateral vlPAG response. Across PAG voxels, BOLD signal intensity correlated with changes in physiological reactivity (relative to baseline) and showed some evidence of spatial organization along the rostral–caudal axis. These findings suggest that the PAG may have a broader role in coordinating brain—body communication during a minimally to moderately demanding task, even in the absence of threat.
Replication in the presence of dengue convalescent serum impacts Zika virus neutralization sensitivity and fitness
Authors: Marano Jeffrey M. , Weger-Lucarelli James 
Published: December 2022

AbstractFlaviviruses like dengue virus (DENV) and Zika virus (ZIKV) are mosquito-borne viruses that cause febrile, hemorrhagic, and neurological diseases in humans, resulting in 400 million infections annually. Due to their co-circulation in many parts of the world, flaviviruses must replicate in the presence of pre-existing adaptive immune responses targeted at serologically closely related pathogens, which can provide protection or enhance disease. However, the impact of pre-existing cross-reactive immunity as a driver of flavivirus evolution, and subsequently the implications on the emergence of immune escape variants, is poorly understood. Therefore, we investigated how replication in the presence of convalescent dengue serum drives ZIKV evolution. We used anin vitrodirected evolution system, passaging ZIKV in the presence of serum from humans previously infected with DENV (anti-DENV) or serum from DENV-naïve patients (control serum). Following five passages in the presence of serum, we performed next-generation sequencing to identify mutations that arose during passaging. We studied two non-synonymous mutations found in the anti-DENV passaged population (E-V355I and NS1-T139A) by generating individual ZIKV mutants and assessing fitness in mammalian cells and live mosquitoes, as well as their sensitivity to antibody neutralization. Both viruses had increased fitness in Vero cells with and without the addition of anti-DENV serum and in human lung epithelial and monocyte cells. In Aedes aegypti mosquitoes—using blood meals with and without anti-DENV serum—the mutant viruses had significantly reduced fitness compared to wild-type ZIKV. These results align with the trade-off hypothesis of constrained mosquito-borne virus evolution. Notably, only the NS1-T139A mutation escaped neutralization, while E-V335I demonstrated enhanced neutralization sensitivity to neutralization by anti-DENV serum, indicating that neutralization escape is not necessary for viruses passaged under cross-reactive immune pressures. Future studies are needed to assess cross-reactive immune selection in humans and relevant animal models or with different flaviviruses.
Neural circuit mechanisms for transforming learned olfactory valences into wind-oriented movement
Authors: Aso Yoshinori , Yamada Daichi , Bushey Daniel , Hibbard Karen , Sammons Megan , Otsuna Hideo , Shuai Yichun , Hige Toshihide 
Published: December 2022

SummaryHow memories are used by the brain to guide future action is poorly understood. In olfactory associative learning in Drosophila, multiple compartments of the mushroom body act in parallel to assign valence to a stimulus. Here, we show that appetitive memories stored in different compartments induce different levels of upwind locomotion. Using a photoactivation screen of a new collection of split-GAL4 drivers and EM connectomics, we identified a cluster of neurons postsynaptic to the mushroom body output neurons (MBONs) that can trigger robust upwind steering. These UpWind Neurons (UpWiNs) integrate inhibitory and excitatory synaptic inputs from MBONs of appetitive and aversive memory compartments, respectively. After training, disinhibition from the appetitive-memory MBONs enhances the response of UpWiNs to reward-predicting odors. Blocking UpWiNs impaired appetitive memory and reduced upwind locomotion during retrieval. Photoactivation of UpWiNs also increased the chance of returning to a location where activation was initiated, suggesting an additional role in olfactory navigation. Thus, our results provide insight into how learned abstract valences are gradually transformed into concrete memory-driven actions through divergent and convergent networks, a neuronal architecture that is commonly found in the vertebrate and invertebrate brains.
Development of nuclear microsatellite markers in Yerba mate (Ilex paraguariensisSt. Hil., Aquifoliaceae Bartl.) from whole-genome sequence data
Authors: Tassano Carolina , Olano Rodrigo A. , Gaiero Paola , Vaio Magdalena , Speranza Pablo R. 
Published: December 2022

AbstractIlex paragariensisSt. Hil. (yerba mate) (Aquifoliaceae Bartl.) is a plant species with great economic and cultural importance because its leaves are processed and ground to make infusions like mate or tereré. The species is distributed in a continuous area that includes southern Brazil, and part of Paraguay and Argentina. Uruguay represents the southern distribution limit of the species, where small populations can be found as part of riparian forests. Although there are previous reports of molecular markers for this and other species in the genus, the available markers were not informative enough to represent the intra and interpopulation genetic diversity in these marginal populations. In this study, we developed highly informative nuclear polymorphic microsatellite markers to optimize genetic studies inI. paraguariensis. Markers were identified in contigs from the genome sequence of two individuals and then tested for amplification and polymorphism in a diverse panel and at population level. Markers which passed these tests detected levels of heterozygosity similar to those reported for Brazilian populations and great diversity within populations from Uruguay. This set of markers were successfully multiplexed, substantially reducing the costs of the analysis. In combination with previously reported nuclear and plastid markers, they can be used to evaluate the genetic diversity of rear edge populations, identify genotypes for paternity studies and provide relevant information for the conservation and management of germplasm.
Physiologic and nanoscale distinctions define glutamatergic synapses in tonic vs phasic neurons
Authors: He Kaikai , Han Yifu , Li Xiling , Hernandez Roberto X. , Riboul Danielle V. , Feghhi Touhid , Justs Karlis A. , Mahneva Olena , Perry Sarah , Macleod Gregory T. , Dickman Dion 
Published: December 2022

ABSTRACTNeurons exhibit a striking degree of functional diversity, each one tuned to the needs of the circuitry in which it is embedded. A fundamental functional dichotomy occurs in activity patterns, with some neurons firing at a relatively constant “tonic” rate, while others fire in bursts - a “phasic” pattern. Synapses formed by tonic vs phasic neurons are also functionally differentiated, yet the bases of their distinctive properties remain enigmatic. A major challenge towards illuminating the synaptic differences between tonic and phasic neurons is the difficulty in isolating their physiological properties. At theDrosophilaneuromuscular junction (NMJ), most muscle fibers are co-innervated by two motor neurons, the tonic “MN-Ib” and phasic “MN-Is”. Here, we employed selective expression of a newly developed botulinum neurotoxin (BoNT-C) transgene to silence tonic or phasic motor neurons. This approach revealed major differences in their neurotransmitter release properties, including probability, short-term plasticity, and vesicle pools. Furthermore, Ca2+imaging demonstrated ~two-fold greater Ca2+influx at phasic neuron release sites relative to tonic, along with enhanced synaptic vesicle coupling. Finally, confocal and super resolution imaging revealed that phasic neuron release sites are organized in a more compact arrangement, with enhanced stoichiometry of voltage-gated Ca2+channels relative to other active zone scaffolds. These data suggest that distinctions in active zone nano-architecture and Ca2+influx collaborate to differentially tune glutamate release at synapses of tonic vs phasic neuronal subtypes.
Mutation divergence over space in tumour expansion
Authors: Li Haiyang , Tu Fengyu , Deng Lijuan , Yang Zixuan , Han Yuqing , Fu Xing , Wang Long , Gu Di , Werner Benjamin , Huang Weini 
Published: December 2022

ABSTRACTMutation accumulation in tumour evolution is one major cause of intra-tumour heterogeneity (ITH), which often leads to drug resistance during treatment. Previous studies with multi-region sequencing have shown that mutation divergence among samples within the patient is common, and the importance of spatial sampling to obtain a complete picture in tumour measurements. However, quantitative comparisons of the relationship between mutation heterogeneity and tumour expansion modes, sampling distances as well as the sampling methods are still few. Here, we investigate how mutations diverge over space by varying the sampling distance and tumour expansion modes using individual based simulations. We measure ITH by the Jaccard index between samples and quantify how ITH increases with sampling distance, the pattern of which holds in various sampling methods and sizes. We also compare the inferred mutation rates based on the distributions of Variant Allele Frequencies (VAF) under different tumour expansion modes and sampling sizes. In exponentially fast expanding tumours, a mutation rate can always be inferred in any sampling size. However, the accuracy compared to the true value decreases when the sampling size decreases, where small sampling sizes result in a high estimate of the mutation rate. In addition, such an inference becomes unreliable when the tumour expansion is slower such as in surface growth.