bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of selfing on speciation through the accumulation of Dobzhansky-Muller incompatibilities
Authors: Xu Kuangyi 
Published: March 2023

AbstractPhylogenetic analyses suggest that self-compatible lineages have higher speciation rates than self-incompatible lineages. However, the effects of selfing on speciation remain unclear. Although a selfing population can resist gene flow from other populations, selfing may increase gene flow from a focal population to other populations. This study investigates the effects of selfing rates of two populations on the waiting time to speciation through the accumulation of Dobzhansky-Muller incompatibilities (DMI). Generally, a higher mean selfing rate of two populations facilitates speciation when incompatibility-controlling alleles are recessive and are weakly selected, and when gene flow is mainly through pollen dispersal instead of seed dispersal. However, the selfing rate difference between two populations can retard speciation, especially when the selfing rate of immigrants remains unchanged after migration. When the selfing rates of two populations differ, speciation may be fastest when the mean selfing rate is intermediate. Given that selfing rates often vary among conspecific populations in plant species, the results indicate that lineages with higher mean selfing rates may not necessarily have higher rates of speciation through the accumulation of DMI, and also call for an estimation of the dependency of speciation rates on selfing rates.
Using Recognition Testing to Support Semantic Learning in Developmental Amnesia
Authors: Elward Rachael , Limond Jennifer , Chareyron Loïc , Ethapemi Janice , Vargha-Khadem Faraneh 
Published: March 2023

AbstractPatients with developmental amnesia (DA) have suffered hippocampal damage in infancy and subsequently shown poor episodic memory, but good semantic memory. It is not clear how patients with DA learn semantic information in the presence of episodic amnesia. However, patients with DA show well-developed recognition memory and these recognition abilities may support semantic learning. We present data from three experiments (two previously described in Elward & Vargha-Khadem, 2018). The first experiment showed that recall tests did not facilitate semantic learning. Patients with DA recalled only 35% of the learned information (controls recalled 80%). The second experiment indicated that multiple-choice recognition tests may facilitate learning. Patients with DA recalled 85% of the learned information. In experiment three, a patient with DA (aged 8 years) took part in a repeated-measures test so that recall learning and recognition learning could be directly compared. The results showed a clear benefit of recognition learning compared to recall learning (76% v. 35%). This finding indicates that young people with extensive hippocampal damage indeed utilise their recognition memory to support the integration of new information into their semantic system. This has important implications for the support of school-aged children with episodic memory difficulties.
The role of self-fertilization in plant colony establishment
Authors: Xu Kuangyi , Reatini Bryan 
Published: March 2023

AbstractIncreased rates of self-fertilization are often found in plant colonies, but the factors driving the observed higher selfing rates remain unclear. Specifically, the higher selfing rates in colonist populations may be due to 1) source populations with a higher selfing rate being more likely to successfully establish colonies (a filter effect), 2) thein situevolution of selfing rate or a plastic selfing rate increase rescuing the colony from extinction, 3) selfing rate evolution post establishment. Using individual-based simulations and eco-evo models, we show that under both single and multiple dispersal, colony establishment may often be driven by a filter effect, due to a higher initial selfing rate and lower genetic load, which are correlated since selfing can purge deleterious mutations. Moreover, the role of the filter effect is weaker under multiple dispersal than single dispersal. The evolution of a higher selfing rate is unlikely to contribute directly to colony establishment. Although selfing rate evolution occurs during the colonization process, most of the selfing rate evolution may occur post establishment. Plasticity in selfing rates is more effective in facilitating colony establishment than the evolution of selfing.
The origin and structural evolution ofde novogenes inDrosophila
Authors: Peng Junhui , Zhao Li 
Published: March 2023

AbstractAlthough previously thought to be unlikely, recent studies have shown thatde novogene origination from previously non-genic sequences is a relatively common mechanism for gene innovation in many species and taxa. These young genes provide a unique set of candidates to study the structural and functional origination of proteins. However, our understanding of their protein structures and how these structures originate and evolve are still limited, due to a lack of systematic studies. Here, we combined high-quality base-level whole genome alignments, bioinformatic analysis, and computational structure modeling to study the origination, evolution, and protein structure of lineage-specificde novogenes. We identified 555de novogene candidates inD. melanogasterthat originated within theDrosophilinaelineage. We found a gradual shift in sequence composition, evolutionary rates, and expression patterns with their gene ages, which indicates possible gradual shifts or adaptations of their functions. Surprisingly, we found little overall protein structural changes forde novogenes in theDrosophilinaelineage. Using Alphafold2, ESMFold, and molecular dynamics, we identified a number ofde novogene candidates with protein products that are potentially well-folded, many of which are more likely to contain transmembrane and signal proteins compared to other annotated protein-coding genes. Using ancestral sequence reconstruction, we found that most potentially well-folded proteins are often born folded. Interestingly, we observed one case where disordered ancestral proteins become ordered within a relatively short evolutionary time. Single-cell RNA-seq analysis in testis showed that although mostde novogenes are enriched in spermatocytes, several youngde novogenes are biased in the early spermatogenesis stage, indicating potentially important but less emphasized roles of early germline cells in thede novogene origination in testis. This study provides a systematic overview of the origin, evolution, and structural changes ofDrosophilinae-specificde novogenes.
Contribution of Implicit Memory to Adaptation of Movement Extent During Reaching Against Unpredictable Spring-Like Loads: Insensitivity to Intentional Suppression of Kinematic Performance
Authors: Lantagne Devon D , Mrotek Leigh Ann , Hoelzle James B , Thomas Danny G , Scheidt Robert A 
Published: March 2023

AbstractWe examined the extent to which intentionally underperforming a goal-directed reaching task impacts how memories of recent performance contribute to sensorimotor adaptation. Healthy human subjects performed computerized cognition testing and an assessment of sensorimotor adaptation wherein they grasped the handle of a horizontal planar robot while making goal-directed out-and-back reaching movements. The robot exerted forces that resisted hand motion with a spring-like load that changed unpredictably between movements. The robotic test assessed how implicit and explicit memories of sensorimotor performance contribute to the compensation for the unpredictable changes in the hand-held load. After each movement, subjects were to recall and report peak movement extent from the previous trial. Subjects performed the tests under two counterbalanced conditions: one where they performed with their best effort, and one where they intentionally suppressed performance. Results from the computerized cognition tests confirmed that subjects understood and complied with task instructions. When suppressing performance during the robotic assessment, subjects demonstrated marked changes in reach precision, time to capture the target, and reaction time. We fit a set of limited memory models to the data to identify how subjects used implicit and explicit memories of recent performance to compensate for the changing loads. In both sessions, subjects used implicit, but not explicit, memories from the most recent trial to adapt reaches to unpredictable spring-like loads. Subjects did not “give up” on large errors, nor did they discount small errors deemed “good enough.” Although subjects clearly suppressed kinematic performance (response timing, movement variability, and self-reporting of reach error), the relative contributions of sensorimotor memories to trial-by-trial variations in task performance did not differ significantly between the two testing conditions. We conclude that intentional performance suppression had minimal impact on how implicit sensorimotor memories contribute to adaptation of unpredictable mechanical loads applied to the hand.
Modeling Tick Populations: An Ecological Test Case for Gradient Boosted Trees
Authors: Manley William , Tran Tam , Prusinski Melissa , Brisson Dustin 
Published: March 2023

AbstractGeneral linear models have been the foundational statistical framework used to discover the ecological processes that explain the distribution and abundance of natural populations. Analyses of the rapidly expanding cache of environmental and ecological data, however, require advanced statistical methods to contend with complexities inherent to extremely large natural data sets. Modern machine learning frameworks such as gradient boosted trees efficiently identify complex ecological relationships in massive data sets, which are expected to result in accurate predictions of the distribution and abundance of organisms in nature. However, rigorous assessments of the theoretical advantages of these methodologies on natural data sets are rare. Here we compare the abilities of gradient boosted and linear models to identify environmental features that explain observed variations in the distribution and abundance of blacklegged tick (Ixodes scapularis) populations in a data set collected across New York State over a ten-year period. The gradient boosted and linear models use similar environmental features to explain tick demography, although the gradient boosted models found non-linear relationships and interactions that are difficult to anticipate and often impractical to identify with a linear modeling framework. Further, the gradient boosted models predicted the distribution and abundance of ticks in years and areas beyond the training data with much greater accuracy than their linear model counterparts. The flexible gradient boosting framework also permitted additional model types that provide practical advantages for tick surveillance and public health. The results highlight the potential of gradient boosted models to discover novel ecological phenomena affecting pathogen demography and as a powerful public health tool to mitigate disease risks.
BioConvert: a comprehensive format converter for life sciences
Authors: Caro Hugo , Dollin Sulyvan , Biton Anne , Brancotte Bryan , Desvillechabrol Dimitri , Dufresne Yoann , Li Blaise , Kornobis Etienne , Lemoine Frédéric , Maillet Nicolas , Perrin Amandine , Traut Nicolas , Néron Bertrand , Cokelaer Thomas 
Published: March 2023

AbstractBioinformatics is a field known for the numerous standards and formats that have been developed over the years. This plethora of formats, sometimes complementary, and often redundant, poses many challenges to bioinformatics data analysts. They constantly need to find the best tool to convert their data into the suitable format, which is often a complex, technical and time consuming task. Moreover, these small yet important tasks are often difficult to make reproducible. To over-come these difficulties, we initiatedBioConvert, a collaborative project to facilitate the conversion of life science data from one format to another.BioConvertaggregates existing software within a single framework and complemented them with original code when needed. It provides a common interface to make the user experience more streamlined instead of having to learn tens of them. Currently,BioConvertsupports about 50 formats and 100 direct conversions in areas such as alignment, sequencing, phylogeny, and variant calling. In addition to being useful for end-users,BioConvertcan also be utilized by developers as a universal benchmarking framework for evaluating and comparing numerous conversion tools. Additionally, we provide a web server implementing an online user-friendly interface toBioConvert, hence allowing direct use for the community.
The Adjuvant Effects of Amphipathic Helical Peptides
Authors: Lyu Jyun-Hong , Liou Gunn-Guang , Wang May , Kan Ming-Chung 
Published: March 2023

AbstractSubunit vaccines are the focus of research in developing new vaccines against infectious diseases. Due to the low immunogenicity of recombinant proteins, adjuvants are required for the activation of humoral and cellular immunity against a protein antigen. In this study, we reported the identification of a novel pathway that can activate humoral immunity against a recombinant protein without inducing inflammatory responses. By fusing an amphipathic helical peptide to GFP, one can increases the immunogenicity of GFP by up to 1000 fold. This enhancement was correlated with the ability of amphipathic helical peptides to bind to cell membranes and cause lysosomal membrane permeabilization. We showed evidence that the amphipathic helical peptide may induce the delivery of antigen across the lysosomal membrane into cytosol. Amphipathic helical peptide fusion provided a new pathway for stimulating immune responses against recombinant proteins.
Functional aberration of cortical neuronal network induced by Aβ42 oligomer
Authors: Ganbat Dulguun , Jeon Jae Kyong , Kim Sang Seong 
Published: March 2023

AbstractAlzheimer’s disease (AD) is a multifactorial disorder that affects cognitive functioning, behavior, and neuronal properties. The neuronal dysfunction is primarily responsible for cognitive decline in AD patients, with many causal factors including plaque accumulation of Aβ42. Neural hyperactivity induced by Aβ42 deposition cause abnormalities in neural networks, leading to alterations in synaptic activity and interneuron dysfunction. Even though neuroimaging techniques elucidated the underlying mechanism in the neural connectivity, precise understanding in cellular level is still elusive. Previously, a few multielectrode array studies examined the neuronal network modulationin vitrocultures revealing relevance of ion channels and the chemical modulators in the presence of Aβ42. In this study, we investigated neuronal connectivity and dynamic changes with high density multielectrode array, particularly in relation to network-wide parameter changes over time. By comparing the neuronal network between normal and Aβ42 treated neuronal cultures, it was possible to discover the direct pathological effect of the Aβ42 oligomer altering the network characteristics. The application of graph theory and center of activity trajectory analysis assessed the consolidation and disassociation of neural networks under Aβ42 oligomer exposure over time. This result can enhance our understanding of how neural networks are affected during AD progression.
A data-driven Boolean model explains memory subsets and evolution in CD8+ T cell exhaustion
Authors: Ildefonso Geena V. , Finley Stacey D. 
Published: March 2023

ABSTRACTT cells play a key role in a variety of immune responses, including infection and cancer. Upon stimulation, naïve CD8+ T cells proliferate and differentiate into a variety of memory and effector cell types; however, failure to clear antigens causes prolonged stimulation of CD8+ T cells, ultimately leading to T cell exhaustion (TCE). The functional and phenotypic changes that occur during CD8+ T cell differentiation are well characterized, but the underlying gene expression state changes are not completely understood. Here, we utilize a previously published data-driven Boolean model of gene regulatory interactions shown to mediate TCE. Our network analysis and modeling reveal the final gene expression states that correspond to TCE, along with the sequence of gene expression patterns that give rise to those final states. With a model that predicts the changes in gene expression that lead to TCE, we could evaluate strategies to inhibit the exhausted state. Overall, we demonstrate that a common pathway model of CD8+ T cell gene regulatory interactions can provide insights into the transcriptional changes underlying the evolution of cell states in TCE.
Downregulation of ribosomal RNA (rRNA) genes in human head and neck squamous cell carcinoma (HNSCC) cells is linked to rDNA promoter hypermethylation
Authors: Priyadarshini Neha , Puppala Navinchandra Venkatarama , Jayaprakash Jayasree Peroth , Khandelia Piyush , Sharma Vivek , Mohannath Gireesha 
Published: March 2023

AbstractEukaryotes carry hundreds of ribosomal RNA (rRNA) genes as tandem arrays, which generate rRNA for protein synthesis. Humans carry ~ 400 rRNA gene copies, which are epigenetically regulated. Dysregulation of rRNA synthesis and ribosome biogenesis are characteristic features of cancers. Targeting aberrant rRNA expression for cancer therapy is being explored. Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent cancers globally. Using quantitative PCR and bisulfite sequencing, we show that rRNA genes are downregulated and their promoters are hypermethylated in HNSCC cell lines. These finding may have relevance for prognosis and diagnosis for HNSCC.
Principles of human pre-60Sbiogenesis
Authors: Broeck Arnaud Vanden , Klinge Sebastian 
Published: March 2023

AbstractDuring early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60Sparticles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60Sassembly intermediates at resolutions of 2.5-3.2 Å. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how GTPases and ATPases couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA processing complex, the rixosome, couples large-scale RNA conformational changes to pre-rRNA processing by the RNA degradation machinery. Our ensemble of human pre-60Sparticles provides a rich foundation to elucidate the molecular principles of ribosome formation.One-Sentence SummaryHigh-resolution cryo-EM structures of human pre-60S particles reveal new principles of eukaryotic ribosome assembly.
Inhibitory input directs astrocyte morphogenesis through glial GABABR
Authors: Cheng Yi-Ting , Luna-Figueroa Estefania , Woo Junsung , Chen Hsiao-Chi , Lee Zhung-Fu , Harmanci Akdes Serin , Deneen Benjamin 
Published: March 2023

AbstractCommunication between neurons and glia plays an important role in establishing and maintaining higher order brain function. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and that its deletion in astrocytes results in a loss of morphological complexity across a host of brain regions and disruption of circuit function. Expression of GABABR in developing astrocytes is regulated in a region-specific manner by SOX9 or NFIA and deletion of these transcription factors results in region-specific defects in astrocyte morphogenesis, which is conferred by interactions with transcription factors exhibiting region-restricted patterns of expression. Together our studies identify input from inhibitory neurons and astrocytic GABABR as universal regulators of morphogenesis, while further revealing a combinatorial code of region-specific transcriptional dependencies for astrocyte development that is intertwined with activity-dependent processes.
The RNA-DNA world and the emergence of DNA-encoded heritable traits
Authors: Roy Suvam , Sengupta Supratim 
Published: March 2023

AbstractThe RNA world hypothesis confers a central role to RNA molecules in information encoding and catalysis. Even though evidence in support of this hypothesis has accumulated from both experiments and computational modelling, the transition from an RNA world to a world where heritable genetic information is encoded in DNA remains an open question. Recent experiments show that both RNA and DNA templates can extend complementary primers using free RNA/DNA nucleotides, either non-enzymatically or in the presence of a replicase ribozyme. Guided by these experiments, we analyse protocellular evolution with an expanded set of reaction pathways made possible through the presence of DNA nucleotides. By en-capsulating these reactions inside three different types of protocellular compartments, each subject to distinct modes of selection, we show how protocells containing DNA-encoded replicases in low copy numbers and replicases in high copy numbers can dominate the population. This is facilitated by a reaction that leads to auto-catalytic synthesis of replicase ribozymes from DNA templates encoding the replicase, after the chance emergence of a replicase through non-enzymatic reactions. Our work unveils a pathway for the transition from an RNA world to a mixed RNA-DNA world characterized by Darwinian evolution, where DNA sequences encode heritable phenotypes.
The impact of uncertainty in hERG binding mechanism onin silicopredictions of drug-induced proarrhythmic risk
Authors: Lei Chon Lok , Whittaker Dominic G. , Mirams Gary R. 
Published: March 2023

AbstractBackground and PurposeDrug-induced reduction of the rapid delayed rectifier potassium current carried by the human Ether-à-go-go-Related Gene (hERG) channel is associated with increased risk of arrhythmias. Recent updates to drug safety regulatory guidelines attempt to capture each drug’s hERG binding mechanism by combiningin vitroassays within silicosimulations. In this study, we investigate the impact onin silicoproarrhythmic risk predictions due to uncertainty in the hERG binding mechanism and physiological hERG current model.Experimental ApproachPossible pharmacological binding models were designed for the hERG channel to account for known and postulated small molecule binding mechanisms. After selecting a subset of plausible binding models for each compound through calibration to available voltage-clamp electrophysiology data, we assessed their effects, and the effects of different physiological models, on proarrhythmic risk predictions.Key ResultsFor some compounds, multiple binding mechanisms can explain the same data produced under the safety testing guidelines, which results in different inferred binding rates. This can result in substantial uncertainty in the predicted torsade risk, which often spans more than one risk category. By comparison, we found that the effect of a different hERG physiological current model on risk classification was subtle.Conclusion and ImplicationsThe approach developed in this study assesses the impact of uncertainty in hERG binding mechanisms on predictions of drug-induced proarrhythmic risk. For some compounds, these results imply the need for additional binding data to decrease uncertainty in safety-critical applications.