bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saltational Episodes of Reticulate Evolution in the Drosophila saltans Species Group
Authors: Prediger Carolina , Ferreira Erina A , Zorzato Samara Videira , Hua-Van Aurélie , Klasson Lisa , Miller Wolfgang J , Yassin Amir , Madi-Ravazzi Lilian 
Published: December 2024

Abstract
Phylogenomics reveals reticulate evolution to be widespread across taxa, but whether reticulation is due to low statistical power or it is a true evolutionary pattern remains a field of study. Here, we investigate the phylogeny and quantify reticulation in the Drosophila saltans species group, a Neotropical clade of the subgenus Sophophora comprising 23 species whose relationships have long been problematic. Phylogenetic analyses revealed conflicting topologies between the X chromosome, autosomes and the mitochondria. We extended the ABBA-BABA test of asymmetry in phylogenetic discordance to cases where no “true” species tree could be inferred, and applied our new test (called 2A2B) to whole genome data and to individual loci. We used four strategies, two based on our new assemblies using either conserved genes or ≥50 kb-long syntenic blocks with conserved collinearity across Neotropical Sophophora, and two consisted of windows from pseudo-reference genomes aligned to either an ingroup or outgroup species. Evidence for reticulation varied among the strategies, being lowest in the synteny-based approach, where it did not exceed ∼7% of the blocks in the most conflicting species quartets. High incidences of reticulation were restricted to three nodes on the tree that coincided with major paleogeographical events in South America. Our results identify possible technical biases in quantifying reticulate evolution and indicate that episodic rapid radiations have played a major role in the evolution of a largely understudied Neotropical clade.
RNA binding by Periphilin plays an essential role in initiating silencing by the HUSH complex
Authors: Bloor Stuart , Wit Niek , Lehner Paul J 
Published: December 2024

Abstract
The human silencing hub (HUSH) complex is a transcription-dependent, epigenetic repressor complex that provides a genome-wide immunosurveillance system for the recognition and silencing of newly-integrated retroelements. The core HUSH complex of TASOR, MPP8 and Periphilin, represses these retroelements through SETDB1-mediated H3K9me3 deposition and MORC2-dependent chromatin compaction. HUSH-dependent silencing is RNA-mediated, yet no HUSH component contains a recognised RNA-binding domain. Here we used an unbiased approach to identify which HUSH component was able to bind RNA and determine whether RNA-binding was essential for HUSH function. We identify Periphilin as the major RNA-binding component of the HUSH complex and show that Periphilin's N-terminal domain is essential for both RNA binding and HUSH function. Periphilin binding to RNA was independent of its interaction with TASOR or MPP8, as its N-terminal domain was sufficient for RNA targeting. The artificial tethering of Periphilin to a HUSH-insensitive, nascent transcript, enabled the HUSH-dependent silencing of the transcript. This tethering of Periphilin allowed the RNA-binding region of Periphilin to be removed such that only its C-terminal domain was required for oligomerisation and interaction with TASOR. We therefore show that Periphilin is the predominant RNA-binding protein of the HUSH complex and this RNA-binding is essential for HUSH activity.
Translation of circular RNAs
Authors: Margvelani Giorgi , Maquera Karol Andrea Arizaca , Welden Justin Ralph , Rodgers David W , Stamm Stefan 
Published: December 2024

Abstract
Circular RNAs (circRNAs) are covalently closed RNAs that are present in all eukaryotes tested. Recent RNA sequencing (RNA-seq) analyses indicate that although generally less abundant than messenger RNAs (mRNAs), over 1.8 million circRNA isoforms exist in humans, much more than the number of currently known mRNA isoforms. Most circRNAs are generated through backsplicing that depends on pre-mRNA structures, which are influenced by intronic elements, for example, primate-specific Alu elements, leading to species-specific circRNAs. CircRNAs are mostly cytosolic, stable and some were shown to influence cells by sequestering miRNAs and RNA-binding proteins. We review the increasing evidence that circRNAs are translated into proteins using several cap-independent translational mechanisms, that include internal ribosomal entry sites, N6-methyladenosine RNA modification, adenosine to inosine RNA editing and interaction with the eIF4A3 component of the exon junction complex. CircRNAs are translated under conditions that favor cap-independent translation, notably in cancer and generate proteins that are shorter than mRNA-encoded proteins, which can acquire new functions relevant in diseases.
Detecting a wide range of epitranscriptomic modifications using a nanopore-sequencing-based computational approach with 1D score-clustering
Authors: Vujaklija Ivan , Biđin Siniša , Volarić Marin , Bakić Sara , Li Zhe , Foo Roger , Liu Jianjun , Šikić Mile 
Published: December 2024

Abstract
To date, over 40 epigenetic and 300 epitranscriptomic modifications have been identified. However, current short-read sequencing-based experimental methods can detect &lt;10% of these modifications. Integrating long-read sequencing technologies with advanced computational approaches, including statistical analysis and machine learning, offers a promising new frontier to address this challenge. While supervised machine learning methods have achieved some success, their usefulness is restricted to a limited number of well-characterized modifications. Here, we introduce Modena, an innovative unsupervised learning approach utilizing long-read nanopore sequencing capable of detecting a broad range of modifications. Modena outperformed other methods in five out of six benchmark datasets, in some cases by a wide margin, while being equally competitive with the second best method on one dataset. Uniquely, Modena also demonstrates consistent accuracy on a DNA dataset, distinguishing it from other approaches. A key feature of Modena is its use of ‘dynamic thresholding’, an approach based on 1D score-clustering. This methodology differs substantially from the traditional statistics-based ‘hard-thresholds.’ We show that this approach is not limited to Modena but has broader applicability. Specifically, when combined with two existing algorithms, ‘dynamic thresholding’ significantly enhances their performance, resulting in up to a threefold improvement in F1-scores.
Motif distribution in genomes gives insights into gene clustering and co-regulation
Authors: Chakraborty Atreyi , Chopde Sumant , Madhusudhan Mallur Srivatsan 
Published: December 2024

Abstract
We read the genome as proteins in the cell would – by studying the distributions of 5–6 base motifs of DNA in the whole genome or smaller stretches such as parts of, or whole chromosomes. This led us to some interesting findings about motif clustering and chromosome organization. It is quite clear that the motif distribution in genomes is not random at the length scales we examined: 1 kb to entire chromosomes. The observed-to-expected (OE) ratios of motif distributions show strong correlations in pairs of chromosomes that are susceptible to translocations. With the aid of examples, we suggest that similarity in motif distributions in promoter regions of genes could imply co-regulation. A simple extension of this idea empowers us with the ability to construct gene regulatory networks. Further, we could make inferences about the spatial proximity of genomic fragments using these motif distributions. Spatially proximal regions, as deduced by Hi-C or pcHi-C, were ∼3.5 times more likely to have their motif distributions correlated than non-proximal regions. These correlations had strong contributions from the CTCF protein recognizing motifs which are known markers of topologically associated domains. In general, correlating genomic regions by motif distribution comparisons alone is rife with functional information.
Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation
Authors: Kok Gautam , Schene Imre F , Ilcken Eveline F , Alcaraz Paula Sobrevals , Mendes Marisa I , Smith Desiree E C , Salomons Gajja , Shehata Sawsan , Jans Judith J M , Maroofian Reza , Hoek Tim A , van Es Robert M , Rehmann Holger , Nieuwenhuis Edward E S , Vos Harmjan R , Fuchs Sabine A 
Published: December 2024

Abstract
Aminoacyl-tRNA synthetases (ARSs) couple tRNAs with their corresponding amino acids. While ARSs can bind structurally similar amino acids, extreme specificity is ensured by subsequent editing activity. Yet, we found that upon isoleucine (I) restriction, healthy fibroblasts consistently incorporated valine (V) into proteins at isoleucine codons, resulting from misacylation of tRNAIle with valine by wildtype IARS1. Using a dual-fluorescent reporter of translation, we found that valine supplementation could fully compensate for isoleucine depletion and restore translation to normal levels in healthy, but not IARS1 deficient cells. Similarly, the antiproliferative effects of isoleucine deprivation could be fully restored by valine supplementation in healthy, but not IARS1 deficient cells. This indicates I &gt; V substitutions help prevent translational termination and maintain cellular function in human primary cells during isoleucine deprivation. We suggest that this is an example of a more general mechanism in mammalian cells to preserve translational speed at the cost of translational fidelity in response to (local) amino acid deficiencies.
High throughput variant libraries and machine learning yield design rules for retron gene editors
Authors: Crawford Kate D , Khan Asim G , Lopez Santiago C , Goodarzi Hani , Shipman Seth L 
Published: December 2024

Abstract
The bacterial retron reverse transcriptase system has served as an intracellular factory for single-stranded DNA in many biotechnological applications. In these technologies, a natural retron non-coding RNA (ncRNA) is modified to encode a template for the production of custom DNA sequences by reverse transcription. The efficiency of reverse transcription is a major limiting step for retron technologies, but we lack systematic knowledge of how to improve or maintain reverse transcription efficiency while changing the retron sequence for custom DNA production. Here, we test thousands of different modifications to the Retron-Eco1 ncRNA and measure DNA production in pooled variant library experiments, identifying regions of the ncRNA that are tolerant and intolerant to modification. We apply this new information to a specific application: the use of the retron to produce a precise genome editing donor in combination with a CRISPR-Cas9 RNA-guided nuclease (an editron). We use high-throughput libraries in Saccharomyces cerevisiae to additionally define design rules for editrons. We extend our new knowledge of retron DNA production and editron design rules to human genome editing to achieve the highest efficiency Retron-Eco1 editrons to date.
New developments for the Quest for Orthologs benchmark service
Authors: Altenhoff Adrian , Nevers Yannis , Tran Vinh , Jyothi Dushyanth , Martin Maria , Cosentino Salvatore , Majidian Sina , Marcet-Houben Marina , Fuentes-Palacios Diego , Persson Emma , Walsh Thomas , Lecompte Odile , Gabaldón Toni , Kelly Steven , Hu Yanhui , Iwasaki Wataru , Capella-Gutierrez Salvador , Dessimoz Christophe , Thomas Paul D , Ebersberger Ingo , Sonnhammer Erik 
Published: December 2024

Abstract
The Quest for Orthologs (QfO) orthology benchmark service (https://orthology.benchmarkservice.org) hosts a wide range of standardized benchmarks for orthology inference evaluation. It is supported and maintained by the QfO consortium, and is used to gather ortholog predictions and to examine strengths and weaknesses of newly developed and existing orthology inference methods. The web server allows different inference methods to be compared in a standardized way using the same proteome data. The benchmark results are useful for developing new methods and can help researchers to guide their choice of orthology method for applications in comparative genomics and phylogenetic analysis. We here present a new release of the Orthology Benchmark Service with a new benchmark based on feature architecture similarity as well as updated reference proteomes. We further provide a meta-analysis of the public predictions from 18 different orthology assignment methods to reveal how they relate in terms of ortholog predictions and benchmark performance. These results can guide users of orthologs to the best suited method for their purpose.
One-core neuron deep learning for time series prediction
Authors: Peng Hao , Chen Pei , Yang Na , Aihara Kazuyuki , Liu Rui , Chen Luonan 
Published: December 2024

ABSTRACT
The enormous computational requirements and unsustainable resource consumption associated with massive parameters of large language models and large vision models have given rise to challenging issues. Here, we propose an interpretable ‘small model’ framework characterized by only a single core-neuron, i.e. the one-core-neuron system (OCNS), to significantly reduce the number of parameters while maintaining performance comparable to the existing ‘large models’ in time-series forecasting. With multiple delay feedback designed in this single neuron, our OCNS is able to convert one input feature vector/state into one-dimensional time-series/sequence, which is theoretically ensured to fully represent the states of the observed dynamical system. Leveraging the spatiotemporal information transformation, the OCNS shows excellent and robust performance in forecasting tasks, in particular for short-term high-dimensional systems. The results collectively demonstrate that the proposed OCNS with a single core neuron offers insights into constructing deep learning frameworks with a small model, presenting substantial potential as a new way for achieving efficient deep learning.
A deep learning framework for in silico screening of anticancer drugs at the single-cell level
Authors: Zhang Peijing , Wang Xueyi , Cen Xufeng , Zhang Qi , Fu Yuting , Mei Yuqing , Wang Xinru , Wang Renying , Wang Jingjing , Ouyang Hongwei , Liang Tingbo , Xia Hongguang , Han Xiaoping , Guo Guoji 
Published: December 2024

ABSTRACT
Tumor heterogeneity plays a pivotal role in tumor progression and resistance to clinical treatment. Single-cell RNA sequencing (scRNA-seq) enables us to explore heterogeneity within a cell population and identify rare cell types, thereby improving our design of targeted therapeutic strategies. Here, we use a pan-cancer and pan-tissue single-cell transcriptional landscape to reveal heterogeneous expression patterns within malignant cells, precancerous cells, as well as cancer-associated stromal and endothelial cells. We introduce a deep learning framework named Shennong for in silico screening of anticancer drugs for targeting each of the landscape cell clusters. Utilizing Shennong, we could predict individual cell responses to pharmacologic compounds, evaluate drug candidates’ tissue damaging effects, and investigate their corresponding action mechanisms. Prioritized compounds in Shennong's prediction results include FDA-approved drugs currently undergoing clinical trials for new indications, as well as drug candidates reporting anti-tumor activity. Furthermore, the tissue damaging effect prediction aligns with documented injuries and terminated discovery events. This robust and explainable framework has the potential to accelerate the drug discovery process and enhance the accuracy and efficiency of drug screening.
Achieving High Protein Quality Is a Challenge in Vegan Diets: A Narrative Review
Authors: Soh Bi Xue Patricia , Smith Nick W , von Hurst Pamela R , McNabb Warren C 
Published: December 2024

Abstract
The transition toward plant-based (PB) diets has gained attention as a plausible step toward achieving sustainable and healthy dietary goals. However, the complete elimination of all animal-sourced foods from the diet (ie, a vegan diet) may have nutritional ramifications that warrant close examination. Two such concerns are the adequacy and bioavailability of amino acids (AAs) from plant-sourced foods and the consequences for older vegan populations who have elevated AA requirements. This narrative review describes the challenges of achieving high protein quality from vegan diets. Data were synthesized from peer-reviewed research articles and reviews. Plant-sourced proteins provide poorer distribution of indispensable AAs (IAAs) and have poorer digestibility, partly due to their inherent structural components within the food matrix. The review addresses complexities of combinations of varied plant protein sources and why the inclusion of novel PB alternatives adds uncertainty to the achievement of adequate protein adequacy. Meal distribution patterns of protein and the ensuing physiological impacts deserve further research and are outlined in this review. Particular attention is given to describing the challenges of achieving sufficient protein and IAA intakes by aging populations who choose to follow a vegan diet. This review contributes to the emerging discussions of nutritional risks associated with vegan diets and adds perspective to the current dietary shifts toward PB diets.
Self-reported symptoms or activity limitations and job loss during the COVID-19 pandemic in Japan
Authors: Okahara S , Fujino Y , Nagata T , Kuwamura M , Mafune K , Muramatsu K , Tateishi S , Ogami A , Mori K ,   for the CORoNaWork project
Published: December 2024

Abstract

Background
Previous studies have reported the impact of a diagnosed disease or self-perceived poor overall health on job loss. However, evidence is lacking on which self-reported symptoms or activity limitations are related to job loss, especially during the coronavirus disease 2019 (COVID-19) pandemic.

Aims
We investigated whether self-reported symptoms or activity limitations were correlated with the occurrence of job loss within 1 year during the COVID-19 pandemic.

Methods
In this prospective cohort study, we used questionnaires administered to Japanese workers. A baseline survey conducted in December 2020 was used to determine workers’ symptoms or activity limitations. Experiencing job loss since the baseline survey was ascertained with a follow-up survey in December 2021. The odds ratios of experiencing job loss were estimated using a logistic model with adjusted covariates.

Results
Men (n = 8682) accounted for 58% of the total sample (n = 14 910), and the respondent mean age was 48.2 years. Multivariate analysis showed that workers with pain-related problems; limited physical movement and mobility; fatigue, loss of strength or appetite, fever, dizziness and moodiness; mental health problems; sleep-related problems or eye-related matters had a greater probability of experiencing job loss owing to health reasons.

Conclusions
Several self-reported symptoms or activity limitations can lead to job loss after 1 year, indicating that prevention and resolution of symptoms or activity limitations are important to reduce workers’ risk of losing their jobs.
In-depth characterization of T cell responses with a combined Activation-Induced Marker (AIM) and Intracellular Cytokine Staining (ICS) assay
Authors: Lee Yeji , Tarke Alison , Grifoni Alba 
Published: December 2024

Abstract
Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific T cell immune responses is pivotal to understanding immune function. Commonly used methods for measuring T cell responses include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported. This study describes a combined AIM + ICS assay and the effect of collecting the supernatant. Peripheral blood mononuclear cells (PBMCs) from seven healthy donors were stimulated with DMSO (negative control), Epstein-Barr virus (EBV) peptide pools, and PHA (positive control). The AIM markers OX40 + CD137+ were used for CD4+ T cells and CD69 + CD137+ and CD107a + CD137+ for CD8+ T cells. Cytokine-secreting cells were identified as CD40L+ cytokine+ for CD4+ and CD69+ or CD107 + cytokine+ for CD8+ T cells. Half of the supernatant was collected before adding the BFA/Monensin/CD137 antibody solution to assess the impact on T cell responses. The CD107a + CD137+ AIM markers combination had a lower background than CD69 + CD137+, making CD107a+ a more sensitive marker for CD8+ AIM markers. Collecting half of the supernatant did not significantly affect the immune responses. Our AIM + ICS combined protocol enables the simultaneous assessment of activation and cytokine release reducing the sample volume for testing T cell responses. We also show that collecting half of the supernatant does not significantly interfere with immune responses detection.
Complements and competitors: Examining technological co-diffusion and relatedness on a collaborative coding platform
Authors: Sirianni Antonio D , Morgan Jonathan H , Zöller Nikolas , Rogers Kimberly B , Schröder Tobias 
Published: December 2024

Abstract
Diffusive and contagious processes spread in the context of one another in connected populations. Diffusions may be more likely to pass through portions of a network where compatible diffusions are already present. We examine this by incorporating the concept of “relatedness” from the economic complexity literature into a network co-diffusion model. Building on the “product space” concept used in this work, we consider technologies themselves as nodes in “product networks,” where edges define relationships between products. Specifically, coding languages on GitHub, an online platform for collaborative coding, are considered. From rates of language co-occurrence in coding projects, we calculate rates of functional cohesion and functional equivalence for each pair of languages. From rates of how individuals adopt and abandon coding languages over time, we calculate measures of complementary diffusion and substitutive diffusion for each pair of languages relative to one another. Consistent with the principle of relatedness, network regression techniques (MR-QAP) reveal strong evidence that functional cohesion positively predicts complementary diffusion. We also find limited evidence that functional equivalence predicts substitutive (competitive) diffusion. Results support the broader finding that functional dependencies between diffusive processes will dictate how said processes spread relative to one another across a population of potential adopters.