bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique and Common Agonists Activate the Insect Juvenile Hormone Receptor and the Human AHR
Authors: Sedlak David , Tuma Roman , Kolla Jayaprakash Narayana , Mokhamatam Raveendra Babu , Bahrova Liliia , Lisova Michaela , Bittova Lenka , Jindra Marek 
Published: January 2024

AbstractTranscription factors of the bHLH-PAS family play vital roles in animal development, physiology, and disease. Two members of the family require binding of low-molecular weight ligands for their activity: the vertebrate aryl hydrocarbon receptor (AHR) and the insect juvenile hormone receptor (JHR). In the flyDrosophila melanogaster, the paralogous proteins GCE and MET constitute the ligand-binding component of JHR complexes. Whilst GCE/MET and AHR are phylogenetically heterologous, their mode of action is similar. JHR is targeted by several synthetic agonists that serve as insecticides disrupting the insect endocrine system. AHR is an important regulator of human endocrine homeostasis and it responds to environmental pollutants and endocrine disruptors. Whether AHR signaling is affected by compounds that can activate JHR has not been reported. To address this question, we screened a chemical library of 50,000 compounds to identify 93 novel JHR agonists in a reporter system based onDrosophilacells. Of these compounds, 26% modulated AHR signaling in an analogous reporter assay in a human cell line, indicating a significant overlap in the agonist repertoires of the two receptors. To explore the structural features of agonist-dependent activation of JHR and AHR, we compared the ligand-binding cavities and their interactions with selective and common ligands of AHR and GCE. Molecular dynamics modeling revealed ligand-specific as well as conserved side chains within the respective cavities. Significance of predicted interactions was supported through site-directed mutagenesis. The results have indicated that synthetic insect juvenile hormone agonists might interfere with AHR signaling in human cells.
PredictingAluexonization in the human genome with a deep learning model
Authors: He Zitong , Chen Ou , Phillips Noelani , Pasquesi Giulia Irene Maria , Sabunciyan Sarven , Florea Liliana 
Published: January 2024

AbstractAluexonization, or the recruitment of intronicAluelements into gene sequences, has contributed to functional diversification; however, its extent and the ways in which it influences gene regulation are not fully understood. We developed an unbiased approach to predictAluexonization events from genomic sequences implemented in a deep learning model, eXAlu, that overcomes the limitations of tissue or condition specificity and the computational burden of RNA-seq analysis. The model captures previously reported characteristics of exonizedAlusequences and can predict sequence elements important forAluexonization. Using eXAlu, we estimate the number ofAluelements in the human genome undergoing exonization to be between 55-110K, 11-21 fold more than represented in the GENCODE gene database. Using RT-PCR we were able to validate selected predictedAluexonization events, supporting the accuracy of our method. Lastly, we highlight a potential application of our method to identify polymorphicAluinsertion exonizations in individuals and in the population from whole genome sequencing data.
Hidden route of protein damage through confined oxygen gas
Authors: Kim Seoyoon , Kim Eojin , Park Mingyu , Kim Seong Ho , Kim Byung-Gyu , Sadongo Victor W. , Wijesinghe W.C. Bhashini , Eom Yu-Gon , Yoon Gwangsu , Lee Chaiheon , Jeong Hannah , Kim Chae Un , Myung Kyungjae , Choi Jeong-Mo , Min Seung Kyu , Kwon Tae-Hyuk , Min Duyoung 
Published: January 2024

AbstractOxidative modifications can severely impair protein structure, fold, and function, closely linked to human aging and diseases. Conventional oxidation pathways typically involve the free diffusion of reactive oxygen species (ROS), followed by chemical attacks on the protein surface. Here, we report a hidden route of protein oxidative damage, which we refer to as O2-confinement oxidation pathway. This pathway starts with the initial trapping of dissolved molecular oxygen (O2) within protein cavity spaces, followed by interaction with photosensitizing tryptophan residues. The trapped O2is then converted to singlet oxygen (1O2), a powerful ROS, through spin-flip electron transfer mechanism under blue light. The generated1O2within the protein ultimately attacks the protein core residues through constrained diffusion, accelerating the oxidative damage. This alternative photooxidation pathway through the initial O2trapping would bypass the antioxidant defense systems which target freely-diffusing ROS, constituting an additional layer of protein oxidative damage in cells and tissues.
SEX-SPECIFIC IMPACTS OF EARLY LIFE SLEEP DISRUPTION: ETHANOL SEEKING, SOCIAL INTERACTION, AND ANXIETY ARE DIFFERENTIALLY ALTERED IN ADOLESCENT PRAIRIE VOLES
Authors: Ginder Darren E. , Tinsley Carolyn E. , Kaiser Mara E. , Lim Miranda M. 
Published: January 2024

ABSTRACTEarly life sleep is important for neuronal development and maturation. Using the highly social prairie vole rodent model, we have previously reported that early-life sleep disruption (ELSD) during the pre-weaning period postnatal day (P)14 to 21 results in adult interference with social bonding and increases ethanol consumption following a stressor. Furthermore, we have reported increased parvalbumin expression and reduced glutamatergic neurotransmission in cortical regions in adult prairie voles that experienced this paradigm. To understand the impact of ELSD on the lifespan, examination of an earlier time in life is necessary. Thus, the aim of the present study was to examine the behavioral outcomes of ELSD on adolescent prairie voles. Here we hypothesized that anxiety and reward related behaviors, as measured by light/dark box, 2-bottle choice and social interactions, would be negatively impacted by ELSD in adolescent male and female prairie voles. Male ELSD voles were no different from control voles in measures of anxiety and ethanol preference or consumption, but affiliative social interactions were significantly reduced. ELSD differentially impacted female prairie voles, with increased anxiety-like behavior and reductions in ethanol consumption compared to Controls, but no impact on ethanol preference or social interactions. Together, these results suggest both male and female prairie voles experience differential changes to reward seeking behaviors, but only female prairie voles showed increases in anxiety-like behavior. These results further suggest that early-life sleep is critically important for neurotypical behaviors in adolescence, a time where reward-seeking and risky behaviors are adaptive for learning and promoting survival.
Leveraging Soil Mapping and Machine Learning to Improve Spatial Adjustments in Plant Breeding Trials
Authors: Carroll Matthew E. , Riera Luis G. , Miller Bradley A. , Dixon Philip M. , Ganapathysubramanian Baskar , Sarkar Soumik , Singh Asheesh K. 
Published: January 2024

AbstractSpatial adjustments are used to improve the estimate of plot seed yield across crops and geographies. Moving mean and P-Spline are examples of spatial adjustment methods used in plant breeding trials to deal with field heterogeneity. Within trial spatial variability primarily comes from soil feature gradients, such as nutrients, but study of the importance of various soil factors including nutrients is lacking. We analyzed plant breeding progeny row and preliminary yield trial data of a public soybean breeding program across three years consisting of 43,545 plots. We compared several spatial adjustment methods: unadjusted (as a control), moving means adjustment, P-spline adjustment, and a machine learning based method called XGBoost. XGBoost modeled soil features at (a) local field scale for each generation and per year, and (b) all inclusive field scale spanning all generations and years. We report the usefulness of spatial adjustments at both progeny row and preliminary yield trial stages of field testing, and additionally provide ways to utilize interpretability insights of soil features in spatial adjustments. These results empower breeders to further refine selection criteria to make more accurate selections, and furthermore include soil variables to select for macro– and micro-nutrients stress tolerance.
TEMINET: A Co-Informative and Trustworthy Multi-Omics Integration Network for Diagnostic Prediction
Authors: Luo Haoran , Liang Hong , Liu Hongwei , Fan Zhoujie , Wei Yanhui , Yao Xiaohui , Cong Shan 
Published: January 2024

AbstractAdvancing the domain of biomedical investigation, integrated multi-omics data have shown exceptional performance in elucidating complex human diseases. However, as the variety of omics information expands, precisely perceiving the informativeness of intra- and inter-omics becomes challenging due to the intricate interrelations, thus posing significant obstacles in multi-omics data integration. To address this, we introduce a novel multi-omics integration approach, referred to as TEMINET. This approach enhances diagnostic prediction by leveraging an intra-omics co-informative representation method and a trustworthy learning strategy used to address inter-omics fusion. Considering the multifactorial nature of complex diseases, TEMINET utilizes intra-omics features to construct disease-specific networks, then applies graph attention networks and a multi-level framework to capture more collective informativeness than pairwise relations. To perceive the contribution of co-informative representations within intra-omics, we design a trustworthy learning strategy to identify the reliability of each omics in integration. To integrate inter-omics information, a combined beliefs fusion approach is deployed to harmonize the trustworthy representations of different omics types effectively. Our experiments across four different diseases using mRNA, methylation, and miRNA data demonstrate that TEMINET achieves advanced performance and robustness in classification tasks.
Soil respiration is correlated with rainfall and soil moisture at multiple temporal scales in a seasonal wet tropical forest
Authors: Chakravarthy Dayani , Raghavendra H. V. , Ratnam Jayashree , Sankaran Mahesh 
Published: January 2024

AbstractSoil respiration is the second largest natural flux of carbon (C) between terrestrial ecosystems and the atmosphere, with tropical forests amongst the largest contributors of such soil-derived carbon efflux. With climate change expected to drive changes in both temperature and rainfall, our ability to predict responses of the carbon cycle in the future hinges upon an understanding of how these factors influence soil respiration (Rs). However, these relationships remain poorly characterised across the seasonal tropics, especially south Asia. Here, for two seasonal tropical sites in the Western Ghats of India, we characterised annual, seasonal and temporal variation in Rs and assessed its temperature and moisture sensitivity over 6 years. At both sites, Rs was positively correlated with temperature at the instantaneous scale, but showed no relationship with temperature at seasonal or annual scales. In contrast, Rs showed significant relationships with rainfall and soil moisture at all temporal scales. At the annual scale, respiration was negatively correlated with total annual rainfall. At the seasonal scale, wet season Rs was significantly lower than in the dry season. At the instantaneous scale, Rs showed a parabolic relationship with soil moisture, where soil respiration increased with soil moisture up to ∼21% and decreased beyond that point. Our results suggest that future responses of soil respiration in this seasonal tropical forest will largely be driven by changes in the Indian Summer Monsoon, not only mean annual precipitation, but also the frequency and intensity of extreme rainfall events.
The clade-specific target recognition mechanisms of plant RISCs
Authors: Iwakawa Hiro-oki 
Published: January 2024

AbstractEukaryotic Argonaut proteins (AGOs) assemble RNA-induced silencing complexes (RISCs) with guide RNAs that allow binding to complementary RNA sequences and subsequent silencing of target genes. The model plantArabidopsis thalianaencodes 10 different AGOs, categorized into three distinct clades based on amino acid sequence similarity. While clade 1 and 2 RISCs are known for their roles in post-transcriptional gene silencing, and clade 3 RISCs are associated with transcriptional gene silencing in the nucleus, the specific mechanisms of how RISCs from each clade recognize their targets remain unclear. In this study, I conducted quantitative binding analyses between RISCs and target nucleic acids with mismatches at various positions, unveiling distinct target binding characteristics unique to each clade. Clade 1 and 2 RISCs require base pairing not only in the seed region but also in the 3′ supplementary region for stable target RNA binding, with clade 1 exhibiting a higher stringency. Conversely, clade 3 RISCs tolerate dinucleotide mismatches beyond the seed region. Strikingly, they bind to DNA targets with an affinity equal to or surpassing that of RNA, like prokaryotic AGO complexes. These insights challenge existing views on plant RNA silencing and open avenues for exploring new functions of eukaryotic AGOs.
Compact RNA sensors for increasingly complex functions of multiple inputs
Authors: Choe Christian , Andreasson Johan O. L. , Melaine Feriel , Kladwang Wipapat , Wu Michelle J. , Portela Fernando , Wellington-Oguri Roger , Nicol John J. , Wayment-Steele Hannah K. , Gotrik Michael , Participants Eterna , Khatri Purvesh , Greenleaf William J. , Das Rhiju 
Published: January 2024

ABSTRACTDesigning single molecules that compute general functions of input molecular partners represents a major unsolved challenge in molecular design. Here, we demonstrate that high-throughput, iterative experimental testing of diverse RNA designs crowdsourced from Eterna yields sensors of increasingly complex functions of input oligonucleotide concentrations. After designing single-input RNA sensors with activation ratios beyond our detection limits, we created logic gates, including challenging XOR and XNOR gates, and sensors that respond to the ratio of two inputs. Finally, we describe the OpenTB challenge, which elicited 85-nucleotide sensors that compute a score for diagnosing active tuberculosis, based on the ratio of products of three gene segments. Building on OpenTB design strategies, we created an algorithm Nucleologic that produces similarly compact sensors for the three-gene score based on RNA and DNA. These results open new avenues for diverse applications of compact, single molecule sensors previously limited by design complexity.
DeepRod: A human-in-the-loop system for automatic rodent behavior analysis
Authors: Loy A. , Garafolj M. , Schauerte H. , Behnke H. , Charnier C. , Schwarz P. , Rast G. , Wollmann T. 
Published: January 2024

AbstractWe present a human-in-the-loop system for efficient rodent behavior analysis in drug development. Addressing the time-consuming and labor-intensive nature of manual behavior categorization, this UX-optimized platform integrates AI for complex behavior prediction and active learning to identify rare events. The proposed solution leverages a cloud-native data processing pipeline, AI-based novelty behavior recognition and multi-class classification, demonstrating significant improvements in behavior labeling and discovery.
Impaired Visuospatial Working Memory but Preserved Attentional Control in Bipolar Disorder
Authors: Barnes-Scheufler Catherine V. , Rösler Lara , Schiweck Carmen , Peters Benjamin , Matura Silke , Mayer Jutta S. , Kittel-Schneider Sarah , Schaum Michael , Reif Andreas , Wibral Michael , Bittner Robert A. 
Published: January 2024

ABSTRACTBACKGROUNDPersistent deficits in working memory (WM) and attention have considerable clinical and functional impact in people with bipolar disorder (PBD). Understanding the neurocognitive underpinnings of these interacting cognitive constructs might facilitate the discovery of more effective pro-cognitive interventions. Therefore, we employed a paradigm designed for jointly studying attentional control and WM encoding.METHODSWe used a visuospatial change-detection task using four Gabor Patches with differing orientations in 63 euthymic PBD and 76 healthy controls (HCS), which investigated attentional competition during WM encoding. To manipulate bottom-up attention using stimulus salience, two Gabor patches flickered, which were designated as either targets or distractors. To manipulate top-down attention, the Gabor patches were preceded by either a predictive or a non-predictive cue for the target locations.RESULTSAcross all task conditions, PBD stored significantly less information in visual WM than HCS (significant effect of group). However, we observed no significant group by salience or group by cue interactions. This indicates that impaired WM was not caused by deficits in attentional control.CONCLUSIONSOur results imply that while WM is disturbed in PBD, attentional prioritization of salient targets and distractors as well as the utilization of external top-down cues were not compromised. Consequently, the control of attentional selection appears be intact. These findings provide important constraints for models of WM dysfunction in PBD by indicating that later stages of WM encoding are likely primarily impaired. We also demonstrate that selective attention is not among the main sources of cognitive impairment in PBD.
Insect hosts are nutritional landscapes navigated by fungal pathogens
Authors: De Fine Licht Henrik H. , Csontos Zsuzsanna , Nielsen Piet Jan Domela Nijegaard , Langkilde Enzo Buhl , Hansen August K. Kjærgård , Shik Jonathan Z. 
Published: January 2024

ABSTRACTNutrition can mediate host-pathogen interactions indirectly when specific deficiencies (e.g. iron or glutamine) constrain host immune performance. Nutrition can also directly govern these interactions since invading pathogens colonize finite landscapes of nutritionally variable host tissues that must be optimally foraged during pathogen development. We first used a conceptual framework of nutritional niches to show that insect-pathogenicMetarhiziumfungi navigate host landscapes where different tissues vary widely in (protein (P) and carbohydrates (C)). We next tested whether host-specificMetarhiziumspecies have narrower fundamental nutritional niches (FNN) than host-generalists by measuring pathogen performance across anin vitronutritional landscape simulating a within-host foraging environment. We then tested how developing pathogens navigate nutritional landscapes by developing a liquid-media approach to track pathogen intake of P and C over time. Host-specificity did not govern FNN dimensions as three testedMetarhiziumspecies: 1) grew maximally across C treatments assuming P was present above a lower threshold, and 2) similarly initiated dispersal behaviors and sporulated when either C or P became depleted. However, specialist and generalist pathogens navigated nutritional landscapes differently. The host specialist (M. acridum) first prioritized C intake, but generalists (M. anisopliae,M. robertsii) prioritized P and C according to their availability. Numbers of known hosts may be insufficient to delimit pathogens as specialists or generalists since diverse hosts do not necessarily comprise diverse nutritional landscapes. Instead, immune responses of hosts and nutritional niche breadth of pathogens are likely co-equal evolutionary drivers of host specificity.
B-Cell Involvement in Immune Checkpoint Inhibitor-Induced Lichen Planus: A Comparative Analysis with Non-Drug-Related Lichen Planus
Authors: Tison Alice , Legoupil Delphine , Rochais Marion Le , Hémon Patrice , Foulquier Nathan , Hardy Quentin , Hillion Sophie , Uguen Arnaud , Pers Jacques-Olivier , Misery Laurent , Cornec Divi , Garaud Soizic 
Published: January 2024

ABSTRACTBackgroundImmune checkpoint inhibitors (ICI) have significantly improved cancer prognosis but can lead to immune-related adverse events (irAE), including cutaneous manifestations affecting 30% to 60% of ICI-treated patients. However, the physiopathology of cutaneaous irAE remains unclear.ObjectiveThis study investigated the immune infiltration in tissues affected by cutaneous irAE to elucidate their contribution to the pathogenesis of these toxicities.MethodsSkin biopsies from 6 patients with ICI-induced lichenoid eruptions were compared using imaging mass cytometry to samples from 7 controls with non-drug-related lichen planus.ResultsT cells were the predominant cell type within the inflammatory infiltrate in all samples, but we observed a reduced T-cell infiltration and an increased B-cell frequency in ICI-induced lichen planus compared to non-drug related lichen planus. Among B cells, we observed a significant decrease in IgD-CD27-double-negative B cells and an increase in IgD+CD27-naïve B cells. Spatial analysis demonstrated that infiltrating B cells were organized in aggregates close to T cells in ICI-induced lichen planus.LimitationsThis is a retrospective single-center study with a relatively small sample size.ConclusionThis study sheds light on the involvement of B cells in the pathogenesis of ICI-induced lichen planus, suggesting distinct immunological mechanisms from non-drug-related lichen planus.CAPSULE SUMMARYLichenoid manifestations are a common but understudied side effect occurring in patients receiving anti-PD-1 antibodies.ICI-induced lichen planus displays distinct physiopathology from non-drug-related lichen planus, with a decrease of T-cell infiltration concomitantly to the increase of B cells organized in aggregates.
Morphological deficits of glial cells in a transgenic mouse model for developmental stuttering
Authors: Adeck Afuh , Millwater Marissa , Bragg Camryn , Zhang Ruli , SheikhBahaei Shahriar 
Published: January 2024

AbstractVocal production involves intricate neural coordination across various brain regions. Stuttering, a common speech disorder, has genetic underpinnings, including mutations in lysosomal-targeting pathway genes. Using a Gnptab-mutant mouse model linked to stuttering, we examined neuron and glial cell morphology in vocal production circuits. Our findings revealed altered astrocyte and microglia processes in these circuits in Gnptab-mutant mice, while control regions remained unaffected. Our results shed light on the potential role of glial cells in stuttering pathophysiology and highlight their relevance in modulating vocal production behaviors.
Global spatial potential for implementing land-based climate mitigation
Authors: Beaury Evelyn M. , Smith Jeffrey , Levine Jonathan M. 
Published: January 2024

AbstractLand-based mitigation strategies (LBMS) are critical to reducing climate change and will require large areas for their implementation. Yet few studies have considered how and where LBMS compete for land or are mutually compatible across Earth’s surface. We derived high resolution estimates of the spatial distribution of 19 different LBMS. We estimated 8.9 billion ha suitable for LBMS across the Earth, including 5.6 Bha suitable for only one of the studied strategies and 3.3 Bha suitable for multiple LBMS. We identified significant conflicts between better carbon management of existing land cover types, and restoration-based strategies such as reforestation. At the same time, several agricultural management LBMS were compatible over large areas, including for example, enhanced weathering and improved plantation rotations. Our analysis presents local stakeholders, communities, and governments with the range of LBMS options, and the opportunity costs associated with scaling up any given LBMS to reduce global climate change.