bluuebunny/crossref_metadata_2025_split huggingface dataset:
The three-dimensional anatomy and dorsoventral asymmetry of the matureMarchantia polymorphameristem develops from a symmetrical gemma meristem
Authors: Spencer Victoria , Wallner Eva-Sophie , Jandrasits Katharina , Edelbacher Natalie , Mosiolek Magdalena , Dolan Liam 
Published: August 2024

ABSTRACTMeristems are three-dimensional generative structures that maintain a population of stem cells whilst producing new organs and tissues. Meristems develop in all land plants, however we know relatively little about the spatial and temporal regulation of meristem structure in lineages such as the bryophytes. Here we describe the three-dimensional anatomy of the meristem during the development of the liverwort,Marchantia polymorpha.Using optical reconstructions of the frontal, sagittal and transverse planes through the mature meristem, we show that the apical stem cell is sub-apical, ventral, and located in the outer cell layer. The anatomy of the mature meristem is therefore asymmetrical in the dorsoventral axis, which is reflected by the domain specific protein localisation of Marchantia Class III and Class IV Homeodomain-Leucine-Zippers (MpC3HDZ and MpC4HDZ) and promoter activity of MpYUCCA2. The dorsoventral asymmetry that defines the mature meristem is absent in the juvenile meristems of the asexual propagules known as gemmae. We discovered that anatomical dorsoventral asymmetry of the meristem forms after two days of gemmaling growth and is accompanied by expression of the dorsal identity reporter, MpC3HDZ. We conclude that the gemma meristem is in a state of arrested development and undergoes anatomical rearrangement to develop the three-dimensional meristem structure of the mature plant.
A Comprehensive Evaluation of Self Attention for Detecting Feature Interactions
Authors: Jabeen Saira , Ben-Hur Asa 
Published: August 2024

AbstractUsing deep learning in computational biology requires methods that are able to extract meaningful biological information from the trained models. Although deep learning models excel in their prediction performance, interpreting them presents a challenge. Recent work has suggested that self-attention layers can be interpreted to predict cooperativity between binding of transcription factors. We extend this earlier work and demonstrate that the addition of an entropy term to the loss function yields sparser attention values that are both easier to interpret and provide higher precision interpretations. Furthermore, we performed a comprehensive evaluation of the relative performance of different flavors of attention-based transcription factor cooperativity discovery methods, and compared methods that use raw attention scores to the use of attribution over the attention scores, and the earlier DFIM model. We found that the entropy-enhanced attention-based models performed similarly to each other, and exhibited improved accuracy and reduced computation time compared to DFIM.
Listening to the bats of Carajás: Applied bioacoustics for species inventory and environment use in a mosaic of forests, savannas, and industrial mining in the Brazilian Amazonia
Authors: Gomes Lidiane , Bernard Enrico 
Published: August 2024

AbstractBats emit echolocation calls for orientation, foraging, and social interactions. These calls are mostly species-specific, reliable for inventories and to assess habitat use, characteristics useful for large, species-rich but poorly sampled areas. This is the case of Carajás, in Brazilian Amazonia, a mosaic of cave-rich dense forests and unique metalophilous savannas (known ascanga), harboring a rich bat fauna but also industrial iron ore mining, stressing the need to preserve biodiversity. We used bioacoustics (142,000 minutes of recording) to inventory bats at 61 points in Carajás and identified 43 sonotypes of seven bat families, including species rarely recorded with capture nets. Eleven species were recorded for the first time in Carajás. Species richness varied among environments – forests being the richest – butcangashad greater richness stability and a more distinct species composition. All areas with imminent mining had high bat richness. Richness in a post-mined area increased, possibly indicating resilience of some species. By providing a reference sound library for bats in Carajás, we proved the usefulness of biacoustics to improve the environmental licensing processes involving mining in biodiversity-rich areas, useful not only for Amazonia but also for other tropical environments with high bat species richness.
SQANTI-reads: a tool for the quality assessment of long read data in multi-sample lrRNA-seq experiments
Authors: Keil Netanya , Monzó Carolina , McIntyre Lauren , Conesa Ana 
Published: August 2024

ABSTRACTSQANTI-reads leverages SQANTI3, a tool for the analysis of the quality of transcript models, to develop a read-level quality control framework for replicated long-read RNA-seq experiments. The number and distribution of reads, as well as the number and distribution of unique junction chains (transcript splicing patterns), in SQANTI3 structural categories are informative of raw data quality. Multi-sample visualizations of QC metrics are presented by experimental design factors to identify outliers. We introduce new metrics for 1) the identification of potentially under-annotated genes and putative novel transcripts and for 2) quantifying variation in junction donors and acceptors. We applied SQANTI-reads to two different datasets, aDrosophiladevelopmental experiment and a multi-platform dataset from the LRGASP project and demonstrate that the tool effectively reveals the impact of read coverage on data quality, and readily identifies strong and weak splicing sites. SQANTI-reads is open source and available for download at GitHub.
A latent outcome variable approach for Mendelian randomization using the expectation maximization algorithm
Authors: Amente Lamessa Dube , Mills Natalie T , Le Thuc Duy , Hyppönen Elina , Lee S Hong 
Published: August 2024

AbstractMendelian randomization (MR) is a widely used tool to uncover causal relationships between exposures and outcomes. However, existing MR methods can suffer from inflated type I error rates and biased causal effects in the presence of invalid instruments. Our proposed method enhances MR analysis by augmenting latent phenotypes of the outcome, explicitly disentangling horizontal and vertical pleiotropy effects. This allows for explicit assessment of the exclusion restriction assumption and iteratively refines causal estimates through the expectation-maximization algorithm. This approach offers a unique and potentially more precise framework compared to existing MR methods. We rigorously evaluate our method against established MR approaches across diverse simulation scenarios, including balanced and directional pleiotropy, as well as violations of the Instrument Strength Independent of Direct Effect (InSIDE) assumption. Our findings consistently demonstrate superior performance of our method in terms of controlling type I error rates, bias, and robustness to genetic confounding. Additionally, our method facilitates testing for directional horizontal pleiotropy and outperforms MR-Egger in this regard, while also effectively testing for violations of the InSIDE assumption. We apply our method to real data, demonstrating its effectiveness compared to traditional MR methods. This analysis reveals the causal effects of body mass index (BMI) on metabolic syndrome (MetS) and a composite MetS score calculated by the weighted sum of its component factors. While the causal relationship is consistent across most methods, our proposed method shows fewer violations of the exclusion restriction assumption, especially for MetS scores where horizontal pleiotropy persists and other methods suffer from inflation.
Adaptation to yeast restriction through the evolution of resource acquisition, macronutrient reserve, and ovarian function
Authors: Dasgupta Purbasha , Koner Anish , Pal Rabi Sankar , Pradhan Pranav Nandan , Roychoudhury Kingkini , Nandy Bodhisatta 
Published: August 2024

AbstractOptimization of reproduction under dietary adversity is an important aspect of diet-dependent adaptation. Yet, little is known about the mechanism of such adaptive evolution. Here, we investigated a set of experimentally evolved populations ofDrosophila melanogasterwhere early-life fecundity evolved as an adaptation to chronic protein restriction. We tested the role of resource acquisition and macronutrient storage, and changes in ovarian function that could have allowed such reproductive adaptation. We show that higher early-life fecundity was associated with the increased larval feeding rate, aiding in accumulation of higher protein content at the time of eclosion. Further evidence also suggests increase in reproductively allocated lipid content. Evolved females were found to have larger ovaries that also had a higher number of mature, post-vitellogenic oocytes that seem to readily allow the attainment of higher fecundity. Our results further show the evolution of plasticity in ovariole count (depending on mating status) and total egg-chamber count in females. These results are important in understanding the putative role of genetic variance and covariances that aid or limit the evolution of reproductive optimization, especially under nutritional adversity.
Revisiting acyclovir dosing for viral encephalitis using a Bayesian PBPK modeling approach
Authors: Sun Ming , Manson Martijn L. , Märtson Anne-Grete , Bodilsen Jacob , de Lange Elizabeth C.M. , Guo Tingjie 
Published: August 2024

AbstractAcyclovir is a primary treatment for central nervous system (CNS) infections caused by herpes simplex virus (HSV) and varicella-zoster virus (VZV). However, patient outcomes remain suboptimal with high mortality and morbidity, following current dosing guidelines. Given the lack of alternative therapies, there is a pressing need to optimize acyclovir dosing, especially since initial regimens were developed in the 1980s with incomplete pharmacokinetic data in the CNS. This study aimed to evaluate both current and alternative acyclovir dosing regimens using a full Bayesian physiologically-based pharmacokinetic (PBPK) model tailored for viral encephalitis. We developed a CNS PBPK model to simulate acyclovir concentrations in plasma, brain extracellular fluid (ECF), and subarachnoid space (SAS). Drug efficacy was assessed using two pharmacokinetic targets, 50%fT>IC50and Cmin>IC50, with a safety threshold set at 25 mg/L in plasma. The standard dosing regimen (10 mg/kg TID) yielded sufficient acyclovir exposure in plasma, brain extracellular fluid (ECF), and subarachnoid space (SAS) compartments based on the 50%fT>IC50target. However, it did not consistently meet the Cmin>IC50target, indicating potential suboptimal exposure in these compartments when evaluated against this criterion. Notably, a higher probability of target attainment (PTA) was generally observed in the brain ECF and SAS compared to plasma. Increasing the dosing frequency to QID improved target attainment but exceeded the toxicity threshold at 20 mg/kg. Our findings suggest that a dosing regimen of 10 mg/kg or 15 mg/kg QID may offer a more effective and safer approach for managing CNS infections compared to the other tested alternative dosing regimens.
Hypertension, Intracranial Arteriosclerosis, and Structural Brain Changes in Patients with TIA or Ischemic Stroke
Authors: Li Xi , Berghout Bernhard P. , van Rooijen Gijs , Ikram M. Kamran , Roozenbeek Bob , Bos Daniel 
Published: August 2024

AbstractBackgroundHypertension is a major risk factor of structural brain changes, including atrophy and cerebral small vessel disease. Intracranial arteriosclerosis could be an underlying mechanism between hypertension and structural brain changes. This study investigated whether intracranial carotid artery calcification (ICAC), as a proxy for intracranial arteriosclerosis, explains the association between hypertension and structural brain changes in patients with TIA or ischemic stroke.Methods968 patients (mean age 62.7 years) with TIA or ischemic stroke from a registry study who underwent non-contrast CT (NCCT) and CT-angiography (CTA) were included in this cross-sectional study. Presence and volume (mm3) of ICAC were assessed on CTA. Subtypes of ICAC were assessed on NCCT, where ICAC was categorized into intimal and internal elastic lamina (IEL) type calcification. Structural brain changes, indicated by atrophy, periventricular and deep white matter lesions (WML), and lacunes were assessed on NCCT. Causal mediation analysis was performed using ICAC, ICAC volume, and ICAC subtypes as mediators.ResultsICAC was prevalent in 67.8% of patients, with 52.6% of them exhibiting intimal calcification, and 26.5% exhibiting IEL calcification. Atrophy, periventricular WML, deep WML, and lacunes were present in 48.1%, 56.4%, 43.0% and 17.1% of patients respectively. The presence of ICAC explained 7.1% of the association of hypertension with periventricular WML, 3.6% with deep WML, and 17.6% with lacunes. Hypertension was associated with increased atrophy through ICAC (OR: 1.02, 95% CI: 1.00-1.05). In subgroup analyses, IEL calcification partly explained the association between hypertension and periventricular WML (16.8%), and atrophy (OR: 1.12, 95% CI: 1.02-1.27). Intimal calcification did not explain any association.ConclusionICAC partially explained the association between hypertension and atrophy, periventricular and deep WML, and lacunes. Although intimal calcification was more prevalent in ischemic stroke patients, IEL calcification takes the leading role in explaining the association between hypertension and structural brain changes.
Cellular and molecular networks of intercellular signaling in bone marrow hematopoiesis
Authors: Thomas Zachary V. , Wang Bowen , Boohar Wade R. , Vergel Mary , Eerdeng Jiya , Shon Dayeon J. , Elowitz Michael B. , Lu Rong 
Published: August 2024

AbstractHematopoietic stem and progenitor cells (HSPCs) rely on intercellular signaling to maintain and adjust their production of blood and immune cells. This process occurs in the semi-fluidic bone marrow, hosting dozens of cell types that constantly migrate and interact. To elucidate the dynamic network of cell-cell interaction and signaling transduction underlying hematopoiesis, we developed an algorithm to measure Cell-cell Spatial Interaction Probability (CellSIP) by integrating data on ligand and receptor expression, cell type abundance, and cellular spatial positioning. Using new and published mouse datasets, we validated CellSIP and uncovered signaling transductions indicating feedback mechanisms underlying hematopoiesis. Moreover, we identified significant correlations between signaling pathways across individual HSPCs at the same hematopoiesis stage. These pathway correlations illuminate the organization of cellular and signaling networks underlying hematopoiesis, revealing new regulators through their associations with established ones. The signaling quantification and correlation data are available through the Hematopoiesis Intercellular Signaling Explorer (HISE).
Exploitation of phylum-spanning omics resources reveals complexity in the nematode FLP signalling system and provides insights intoflp-gene evolution
Authors: McCoy Ciaran J. , Wray Christopher , Freeman Laura , Crooks Bethany A. , Golinelli Luca , Marks Nikki J. , Temmerman Liesbet , Beets Isabel , Atkinson Louise E. , Mousley Angela 
Published: August 2024

AbstractBackgroundParasitic nematodes significantly undermine global human and animal health and productivity. Parasite control is reliant on anthelmintic administration however over-use of a limited number of drugs has resulted in escalating parasitic nematode resistance, threatening the sustainability of parasite control and underscoring an urgent need for the development of novel therapeutics. FMRFamide-like peptides (FLPs), the largest family of nematode neuropeptides, modulate nematode behaviours including those important for parasite survival, highlighting FLP receptors (FLP-GPCRs) as appealing putative novel anthelmintic targets. Advances in omics resources have enabled the identification of FLPs and neuropeptide-GPCRs in some parasitic nematodes, but remaining gaps in FLP-ligand libraries hinder the characterisation of receptor-ligand interactions, which are required to drive the development of novel control approaches.ResultsIn this study we exploited recent expansions in nematode genome data to identify 2143flp-genes in >100 nematode species across free-living, entomopathogenic, plant, animal and human lifestyles and representing 7 of the 12 major nematode clades (1). Our data reveal that: (i) the phylum-spanningflps, flp-1, −8, −14, and −18, may be representative of theflpprofile of the last common ancestor of nematodes; (ii) the majority of parasitic nematodes have a reducedflpcomplement relative to free-living species; (iii) FLP prepropeptide architecture is variable within and betweenflp-genes and across nematode species; (iv) FLP prepropeptide signatures facilitateflp-gene discrimination; (v) FLP motifs display variable length, amino acid sequence, and conservation; (vi) CLANS analysis provides insight into the evolutionary history offlp-gene sequelogues and reveals putativeflp-gene paralogues and, (viii)flpexpression is upregulated in the infective larval stage of several nematode parasites.ConclusionsThese data provide the foundation required for phylum-spanning FLP-GPCR deorphanisation screens in nematodes to seed the discovery and development of novel parasite control approaches.
Divergent macrophage induced lung pathology occurs between infants and adults during respiratory viral infection
Authors: Verhoeven David , Verhoeven Davis 
Published: August 2024

AbstractYoung children, especially those aged 4 months to 2 years of age, frequently exhibit severe morbidity during respiratory viral infections. For influenza infections, macrophages/monocytes serve as front line defenses against early viral replication in the lungs until the adaptive immune system arrives to clear virus. However, infiltrating inflammatory monocytes are a significant cause of influenza induced lung pathology/morbidity. We utilized a young murine model of respiratory viral infections using 21-day-old mice to investigate the mechanisms driving the heightened influenza induced morbidity observed in human young children. We hypothesized that macrophages/monocytes responses to influenza would diverge between young and older mice despite our evidence that macrophages from both groups appear to control viral replication at similar rates. While inflammatory monocyte infiltration contributed to influenza induced morbidity/lung inflammation in adults, they did not appear to contribute to morbidity in young mice. Instead, young mice appeared to develop lung inflammation through a lack of interferon gamma (IFNψ) and infection of macrophage populations. In contrast, adult mice controlled early viral replication through macrophage populations (alveolar, interstitial, and inflammatory) and inflammatory monocytes. While intrinsic limitations in anti-viral cytokine responses, especially IFNψ, characterized the macrophage response to viral infection in young mice, the innate immune response to infection appears diminished compared to adults. This study highlights the intrinsic limitations in macrophage effector functions that may arise in young children but that also contribute to disease pathology.
mvh: an R tool to assemble and organize virtual herbaria from openly available specimen images
Authors: Vasconcelos Thais , Boyko James D. 
Published: August 2024

AbstractPremiseRecent efforts in digitizing and imaging herbarium specimens have enhanced their use in systematics, ecology, and evolutionary studies. However, there is a lack of user-friendly tools that facilitate the assembly and organizing of customized sets of herbarium specimen images on personal devices, i.e. a personal virtual herbarium.MethodsHere we present the R packagemvh(stands for “my virtual herbarium”), a software that includes functions designed to search and download metadata and openly available images associated with herbarium specimens based on taxon or geography. The download function also includes an argument to resize images according to a user-imputed quality preference.ResultsWe tested the functionalities ofmvhby searching metadata associated with five randomly sampled sets of ten vascular plant species (taxon-based search) and five sets of ten terrestrial coordinates (geography-based search). The main download function had a success rate of 99%, downloading 291 out of the 293 images found in the search. Possible reasons for download failure are also reported as part of the functions’ output.ConclusionsAs long as stable internet connection is available, the R packagemvhmakes the assembly and organizing of personal virtual herbaria an easy task that can help botanists to investigate novel empirical questions as well as trends in digitization efforts.
Challenges in Detecting Somatic Recombination of Repeat Elements: Insights from Short and Long Read Datasets
Authors: Pascarella Giovanni , Frith Martin , Carninci Piero 
Published: August 2024

AbstractNon-allelic copies of the two major families of repeat elements in the human genome, Alu and L1, recombine somatically at high frequency. Tissue-specific recombination profiles are dynamic in cell differentiation and are altered in neurodegeneration, suggesting that somatic recombination of repeat elements can contribute to functional heterogeneity of cells in health and disease. The study of these genomic variants, however, presents several technical challenges related to their extremely low copy number and their sequence content. Here, we address key issues regarding detecting and annotating structural variants derived from recombining repeat elements in NGS data. We show that PCR introduces significant changes of recombination profiles in sequencing libraries and that recombination profiles are affected by the choice of sequencing platform. We refine previous estimates of recombination in single cells by analyzing recombination profiles in PCR-free HG002 datasets sequenced by Oxford Nanopore Technologies and PacBio sequencers while describing several platform-specific differences. We additionally provide evidence that recombination events annotated in state-of-the-art single-cell HG002 whole-genome sequencing datasets are likely molecular artifacts generated by PCR. By exploring the limits of current technologies, this work establishes essential requirements for future developments to enhance the reliability of detecting somatic recombination of repeat elements in genomic datasets.
Optimized search for a binary black hole merger population in LIGO-Virgo O3 data
Authors: Kumar Praveen , Dent Thomas 
Published: August 2024

Maximizing the number of detections in matched filter searches for compact binary coalescence (CBC) gravitational wave signals requires a model of the source population distribution. In previous searches using the framework, sensitivity to the population of binary black hole (BBH) mergers was improved by restricting the range of filter template mass ratios and use of a simple one-dimensional population model. However, this approach does not make use of our full knowledge of the population and cannot be extended to a full parameter space search. Here, we introduce a new ranking method, based on kernel density estimation with adaptive bandwidth, to accurately model the probability distributions of binary source parameters over a template bank, both for signals and for noise events. We demonstrate this ranking method by conducting a search over LIGO-Virgo O3 data for BBHs with unrestricted mass ratio, using a signal model derived from previous significant detected events. We achieve over 10% increase in sensitive volume for a simple power-law simulated signal population, compared to the previous BBH search. Correspondingly, with the new ranking, eight additional candidate events above an inverse false alarm rate threshold 0.5 yr are identified.

Published by the American Physical Society
2024