bluuebunny/crossref_metadata_2025_split huggingface dataset:
Depletion of LONP2 unmasks differential requirements for peroxisomal function between cell types and in cholesterol metabolism
Authors: Yamashita Akihiro , Ignatenko Olesia , Nguyen Mai , Lambert Raphaëlle , Watt Kathleen , Daneault Caroline , Robillard-Frayne Isabelle , Topisirovic Ivan , Rosiers Christine Des , McBride Heidi M. 
Published: March 2023

AbstractPeroxisomes play a central role in tuning metabolic and signaling programs in a tissue- and cell type-specific manner. However, the mechanisms by which the status of peroxisomes is communicated and integrated into cellular signaling pathways is not yet understood. Herein, we report the cellular responses to acute peroxisomal proteotoxic stress upon silencing the peroxisomal protease/chaperone LONP2. Depletion of LONP2 triggered accumulation of its substrates, alterations in peroxisome size and numbers, and luminal protein import failure. Gene expression changes and lipidomic analysis revealed striking cell specific differences in the response to siLONP2. Specific to COS-7 cells was a strong activation of the integrated stress response (ISR) and upregulation of ribosomal biogenesis gene expression levels. Common changes between COS-7 and U2OS cell lines included repression of the retinoic acid signaling pathway, and upregulation of sphingolipids. Cholesterol accumulated in the endomembrane compartments in both cell lines, consistent with evidence that peroxisomes are required for cholesterol flux out of late endosomes. These unexpected consequences of peroxisomal stress provide an important insight for our understanding of the tissue-specific responses seen in peroxisomal disorders.
Decision uncertainty as a context for motor memory
Authors: Ogasa Kisho , Yokoi Atsushi , Okazawa Gouki , Nishigaki Morimichi , Hirashima Masaya , Hagura Nobuhiro 
Published: March 2023

AbstractThe current view of perceptual decision-making suggests that once the decision is made, a single motor program associated with the decision is carried out, irrespective of the degree of uncertainty involved in the decision-making process. As opposed to this view, we show that different levels of decision uncertainty contextualize actions differently, allowing the brain to form different motor memories based on each context. The match between decision uncertainty during learning and retrieval is critical for successful motor memory retrieval. The same movement trajectory can be associated with different motor memories if each memory is linked to a different level of decision uncertainty. Encoding motor memories based on decision contexts may enhance the robustness of control during the varying neural activities induced by different cognitive states.
Human relevant exposure to di-n-butyl phthalate tampers with the ovarian insulin-like growth factor 1 system and disrupts folliculogenesis in young adult mice
Authors: Jauregui Estela J. , McSwain Maile , Liu Xiaosong , Miller Kara , Burns Kimberlie , Craig Zelieann R. 
Published: March 2023

ABSTRACTPhthalates are compounds used in consumer and medical products worldwide. Phthalate exposure in women has been demonstrated by detection of phthalate metabolites in their urine and ovarian follicular fluid. High urinary phthalate burden has been associated with reduced ovarian reserve and oocyte retrieval in women undergoing assisted reproduction. Unfortunately, no mechanistic explanation for these associations is available. In short term in vivo and in vitro animal studies modeling human relevant exposures to di-n-butyl phthalate (DBP), we have identified ovarian folliculogenesis as a target for phthalate exposures. In the present study, we investigated whether DBP exposure negatively influences insulin-like growth factor 1 (IGF) signaling in the ovary and disrupts ovarian folliculogenesis. CD-1 female mice were exposed to corn oil (vehicle) or DBP (10 or 100 μg/kg/day) for 20-32 days. Ovaries were collected as animals reached the proestrus stage to achieve estrous cycle synchronization. Levels of mRNAs encoding IGF1 and 2 (Igf1andIgf2), IGF1 receptor (Igf1r), and IGF binding proteins 1-6 (Ifgbp1-6) were measured in whole ovary homogenates. Ovarian follicle counts and immunostaining for phosphorylated IGF1R protein (pIGF1R) were used to evaluate folliculogenesis and IGF1R activation, respectively. DBP exposure, at a realistic dose that some women may experience (100 μg/kg/day for 20-32 days), reduced ovarianIgf1andIgf1rmRNA expression and reduced small ovarian follicle numbers and primary follicle pIGF1R positivity in DBP-treated mice. These findings reveal that DBP tampers with the ovarian IGF1 system and provide molecular insight into how phthalates could influence the ovarian reserve in females.
Molecular dynamics simulations illuminate the role of sequence context in the ELF3-PrD-based temperature sensing mechanism in plants
Authors: Lindsay Richard J. , Viegas Rafael Giordano , Leite Vitor B. P. , Wigge Philip A. , Hanson Sonya M. 
Published: March 2023

AbstractThe evening complex (EC) is a tripartite DNA repressor and a core component of the circadian clock that provides a mechanism for temperature-responsive growth and development of many plants. ELF3, a component of the EC, is a disordered scaffolding protein that blocks transcription of growth genes at low temperature. At increased temperature EC DNA binding is disrupted and ELF3 is sequestered in a reversible nuclear condensate, allowing transcription and growth to proceed. The condensation is driven by a low complexity prion-like domain (PrD), and the sensitivity of the temperature response is modulated by the length of a variable polyQ tract, with a longer polyQ tract corresponding to enhanced condensate formation and hypocotyl growth at increased temperature. Here, a series of computational studies provides evidence that polyQ tracts promote formation of temperature-sensitive helices in flanking residues with potential impacts for EC stability under increasing temperature. REST2 simulations uncover a heat-induced population of condensation-prone conformations that results from the exposure of ‘sticky’ aromatic residues by temperature-responsive breaking of long-range contacts. Coarse-grained Martini simulations reveal both polyQ tract length and sequence context modulate the temperature dependence of cluster formation. Understanding the molecular mechanism underlying the ELF3-PrD temperature response in plants has implications for technologies including modular temperature-response elements for heat-responsive protein design and agricultural advances to enable optimization of crop yields and allow plants to thrive in increasingly inhospitable environments.
Identification of mammalian transcription factors that bind to inaccessible chromatin
Authors: Pop Romana T. , Pisante Alessandra , Nagy Dorka , Martin Patrick C. N. , Mikheeva Liudmila A , Hayat Ateequllah , Ficz Gabriella , Zabet Nicolae Radu 
Published: March 2023

AbstractTranscription factors (TFs) are proteins that affect gene expression by binding to regulatory regions of DNA in a sequence specific manner. The binding of TFs to DNA is controlled by many factors, including the DNA sequence, concentration of TF, chromatin accessibility and co-factors. Here, we systematically investigated the binding mechanism of hundreds of TFs by analysing ChIP-seq data with our explainable statistical model, ChIPanalyser. This tool uses as inputs the DNA sequence binding motif; the capacity to distinguish between strong and weak binding sites; the concentration of TF; and chromatin accessibility. We asked whether TFs preferred to bind to DNA in open or dense chromatin conformation and found that approximately one third of TFs are predicted to bind the genome in a DNA accessibility independent fashion. Our model predicted this to be the case when the TF binds to its strongest binding regions in the genome, and only a small number of TFs have the capacity to bind dense chromatin at their weakest binding regions, such as CTCF USF2 and CEBPB. Our study demonstrated that the binding of hundreds of human and mouse TFs is predicted by ChIPanalyser with high accuracy and showed that many TFs can bind dense chromatin.
NAC1 directs CEP1-CEP3 peptidase expression and modulates root hair growth in Arabidopsis
Authors: Rodríguez-García Diana R. , Guerrero Yossmayer del Carmen Rondón , Ferrero Lucía , Rossi Andrés Hugo , Miglietta Esteban A. , Aptekmann Ariel A. , Marzol Eliana , Pacheco Javier Martínez , Carignani Mariana , Gabarain Victoria Berdion , Lopez Leonel E. , Dominguez Gabriela Díaz , Borassi Cecilia , Sánchez-Serrano José Juan , Xu Lin , Nadra Alejandro D. , Rojo Enrique , Ariel Federico , Estevez José M. 
Published: March 2023

AbstractPlant genomes encode a unique group of papain-type Cysteine EndoPeptidases (CysEPs) containing a KDEL endoplasmic reticulum (ER) retention signal (KDEL-CysEPs or CEPs). CEPs process the cell-wall scaffolding EXTENSIN proteins (EXTs), which regulatede novocell wall formation and cell expansion. Since CEPs are able to cleave EXTs and EXT-related proteins, acting as cell wall-weakening agents, they may play a role in cell elongation.Arabidopsis thalianagenome encodes three CEPs (AtCPE1-AtCEP3). Here we report that the three Arabidopsis CEPs,AtCEP1-AtCEP3,are highly expressed in root-hair cell files. Single mutants have no evident abnormal root-hair phenotype, butatcep1-3 atcep3-2andatcep1-3 atcep2-2double mutants have longer root hairs (RHs) than wild type (Wt) plants, suggesting that expression ofAtCEPsin root trichoblasts restrains polar elongation of the RH. We provide evidence that the transcription factorNAC1activates AtCEPs expression in roots to limit RH growth. Chromatin immunoprecipitation indicates that NAC1 binds the promoter ofAtCEP1, AtCEP2,and to a lower extent toAtCEP3and may directly regulate their expression. Indeed, inducibleNAC1overexpression increasesAtCEP1 and AtCEP2transcript levels in roots and leads to reduced RH growth while the loss of functionnac1-2mutation reducesAtCEP1-AtCEP3gene expression and enhances RH growth. Likewise, expression of a dominant chimeric NAC1-SRDX repressor construct leads to increased RH length. Finally, we show that RH cell walls in theatcep1-1 atcep3-2double mutant have reduced levels of EXT deposition, suggesting that the defects in RH elongation are linked to alterations in EXT processing and accumulation. Taken together, our results support the involvement of AtCEPs in controlling RH polar growth through EXT-processing and insolubilization at the cell wall.
CanFlyet: Habitat Zone and Diet Trait Dataset for Diptera Species of Canada and Greenland
Authors: Majoros S.E. , Adamowicz S.J. 
Published: March 2023

AbstractBackgroundTrue flies (Diptera) are an ecologically important group that play a role in agriculture, public health and ecosystem functioning. As researchers continue to investigate this order, it is beneficial to link the growing occurrence data to biological traits. However, large-scale ecological trait data are not readily available for fly species. While some databases and datasets include fly data, many ecologically relevant traits for taxa of interest are not included. In this study we create a dataset containing ecological traits (habitat and diet) for fly species of Canada and Greenland having occurrence records on the Barcode of Life Data Systems (BOLD). We present a dataset containing trait information for 981 Diptera species.New InformationDiptera were chosen for the dataset based on the occurrence records available for Diptera species from Canada and Greenland on the Barcode of Life Data Systems (BOLD). Trait data were then compiled based on literature searches conducted from April 2021 - April 2024 and assigned at the lowest taxonomic level possible. Three biological traits were included: habitat, larval diet, and adult diet. The dataset contains traits for 981 species across 380 genera, 34 subfamilies, and 61 families. This dataset allows for assignment of traits to occurrence data for Diptera species and can be used for further research into the ecology, evolution, and conservation of this order.
Accurate estimation of rare cell type fractions from tissue omics data via hierarchical deconvolution
Authors: Huang Penghui , Cai Manqi , Lu Xinghua , McKennan Chris , Wang Jiebiao 
Published: March 2023

AbstractBulk transcriptomics in tissue samples reflects the average expression levels across different cell types and is highly influenced by cellular fractions. As such, it is critical to estimate cellular fractions to both deconfound differential expression analyses and infer cell type-specific differential expression. Since experimentally counting cells is infeasible in most tissues and studies,in silicocellular deconvolution methods have been developed as an alternative. However, existing methods are designed for tissues consisting of clearly distinguishable cell types and have difficulties estimating highly correlated or rare cell types. To address this challenge, we propose Hierarchical Deconvolution (HiDecon) that uses single-cell RNA sequencing references and a hierarchical cell type tree, which models the similarities among cell types and cell differentiation relationships, to estimate cellular fractions in bulk data. By coordinating cell fractions across layers of the hierarchical tree, cellular fraction information is passed up and down the tree, which helps correct estimation biases by pooling information across related cell types. The flexible hierarchical tree structure also enables estimating rare cell fractions by splitting the tree to higher resolutions. Through simulations and real data applications with the ground truth of measured cellular fractions, we demonstrate that HiDecon significantly outperforms existing methods and accurately estimates cellular fractions.
Root system growth and function response to soil temperature in maize (Zea maysL.)
Authors: Clark Randy , Chamberlain Dan , Diepenbrock Christine , Cooper Mark , Messina Carlos D. 
Published: March 2023

AbstractCrop adaptation to the mixture of environments that defines the target population of environments is the result from a balanced resource allocation between roots, shoots and reproductive organs. Root growth places a critical role in the determination of this balance. Root growth and function responses to temperature can determine the strength of roots as sinks but also influence the crop’s ability to uptake water and nutrients. Surprisingly, this behavior has not been studied in maize since the middle of the last century, and the genetic determinants are unknown. Low temperatures often recorded in deep soil layers limit root growth and soil exploration and may constitute a bottleneck towards increasing drought tolerance, nitrogen recovery, sequestration of carbon and productivity in maize. High throughput phenotyping (HTP) systems were developed to investigate these responses and to examine genetic variability therein across diverse maize germplasm. Here we show that there is: 1) genetic variation of root growth under low temperature and below 10°C, and 2) genotypic variation in water transport under low temperature. Using simulation, we demonstrate that the measured variation for both traits contribute to drought tolerance and explain important components of yield variation in the US corn-belt. The trait set examined herein and HTP platform developed for its characterization reveal a unique opportunity to remove a major bottleneck for crop improvement, and adaptation to climate change.
3DMolMS: Prediction of Tandem Mass Spectra from Three Dimensional Molecular Conformations
Authors: Hong Yuhui , Li Sujun , Welch Christopher J. , Tichy Shane , Ye Yuzhen , Tang Haixu 
Published: March 2023

AbstractMotivationTandem mass spectrometry is an essential technology for characterizing chemical compounds at high sensitivity and throughput, and is commonly adopted in many fields. However, computational methods for automated compound identification from their MS/MS spectra are still limited, especially for novel compounds that have not been previously characterized. In recent years,in silicomethods were proposed to predict the MS/MS spectra of compounds, which can then be used to expand the reference spectral libraries for compound identification. However, these methods did not consider the compounds’ three-dimensional (3D) conformations, and thus neglected critical structural information.ResultsWe present the3D Molecular Network forMassSpectra Prediction (3DMolMS), a deep neural network model to predict the MS/MS spectra of compounds from their 3D conformations. We evaluated the model on the experimental spectra collected in several spectral libraries. The results showed that 3DMolMS predicted the spectra with the average cosine similarity of 0.687 and 0.475 with the experimental MS/MS spectra acquired in positive and negative ion modes, respectively. Furthermore, 3DMolMS model can be generalized to the prediction of MS/MS spectra acquired by different labs on different instruments through minor fine-tuning on a small set of spectra. Finally, we demonstrate that themolecular representationlearned by 3DMolMS from MS/MS spectra prediction can be adapted to enhance the prediction of chemical properties such as the elution time (ET) in the liquid chromatography and the Collisional Cross Section (CCS) measured by ion mobility spectrometry (IMS), both of which are often used to improve compound identification.Contacthatang@indiana.eduSupplementary informationThe codes of 3DMolMS is available athttps://github.com/JosieHong/3DMolMSand the web service is athttps://spectrumprediction.gnps2.org.
Social association predicts immunological similarity in rewilded mice
Authors: Downie A. E. , Oyesola O. , Barre R. S. , Caudron Q. , Chen Y.-H. , Dennis E. J. , Garnier R. , Kiwanuka K. , Menezes A. , Navarrete D. J. , Mondragón-Palomino O. , Saunders J. B. , Tokita C. K. , Zaldana K. , Cadwell K. , Loke P. , Graham A. L. 
Published: March 2023

AbstractEnvironmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual’s interaction with its environment. We tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including social associations, to immune phenotypes. We found that the more associated two individuals were, the more similar their immune phenotypes were. Social association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or worm infection status. These results highlight the importance of social networks for immune phenotype and reveal important immunological correlates of social life.
Phase Separation in Mixtures of Prion-Like Low Complexity Domains is Driven by the Interplay of Homotypic and Heterotypic Interactions
Authors: Farag Mina , Borcherds Wade M. , Bremer Anne , Mittag Tanja , Pappu Rohit V. 
Published: March 2023

AbstractPrion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via coupled associative and segregative phase transitions. We previously deciphered how evolutionarily conserved sequence features drive phase separation of PLCDs through homotypic interactions. However, condensates typically encompass a diverse mixture of proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA binding proteins namely, hnRNPA1 and FUS. We find that 1:1 mixtures of the A1-LCD and FUS-LCD undergo phase separation more readily than either of the PLCDs on their own. The enhanced driving forces for phase separation of mixtures of A1-LCD and FUS-LCD arise partly from complementary electrostatic interactions between the two proteins. This complex coacervation-like mechanism adds to complementary interactions among aromatic residues. Further, tie line analysis shows that stoichiometric ratios of different components and their sequence-encoded interactions jointly contribute to the driving forces for condensate formation. These results highlight how expression levels might be tuned to regulate the driving forces for condensate formationin vivo. Simulations also show that the organization of PLCDs within condensates deviates from expectations based on random mixture models. Instead, spatial organization within condensates will reflect the relative strengths of homotypic versus heterotypic interactions. We also uncover rules for how interaction strengths and sequence lengths modulate conformational preferences of molecules at interfaces of condensates formed by mixtures of proteins. Overall, our findings emphasize the network-like organization of molecules within multicomponent condensates, and the distinctive, composition-specific conformational features of condensate interfaces.Significance StatementBiomolecular condensates are mixtures of different protein and nucleic acid molecules that organize biochemical reactions in cells. Much of what we know about how condensates form comes from studies of phase transitions of individual components of condensates. Here, we report results from studies of phase transitions of mixtures of archetypal protein domains that feature in distinct condensates. Our investigations, aided by a blend of computations and experiments, show that the phase transitions of mixtures are governed by a complex interplay of homotypic and heterotypic interactions. The results point to how expression levels of different protein components can be tuned in cells to modulate internal structures, compositions, and interfaces of condensates, thus affording distinct ways to control the functions of condensates.
Remote neuronal activity drives glioma infiltration via Sema4f
Authors: Huang-Hobbs Emmet , Cheng Yi-Ting , Ko Yeunjung , Luna-Figueroa Estefania , Lozzi Brittney , Taylor Kathryn R , McDonald Malcolm , He Peihao , Chen Hsiao-Chi , Yang Yuhui , Maleki Ehson , Lee Zhung-Fu , Murali Sanjana , Williamson Michael , Choi Dongjoo , Curry Rachel , Bayley James , Woo Junsung , Jalali Ali , Monje Michelle , Noebels Jeffrey L , Harmanci Akdes Serin , Rao Ganesh , Deneen Benjamin 
Published: March 2023

AbstractThe tumor microenvironment (TME) plays an essential role in malignancy and neurons have emerged as a key component of the TME that promotes tumorigenesis across a host of cancers. Recent studies on glioblastoma (GBM) highlight bi-directional signaling between tumors and neurons that propagates a vicious cycle of proliferation, synaptic integration, and brain hyperactivity; however, the identity of neuronal subtypes and tumor subpopulations driving this phenomenon are incompletely understood. Here we show that callosal projection neurons located in the hemisphere contralateral to primary GBM tumors promote progression and widespread infiltration. Using this platform to examine GBM infiltration, we identified an activity dependent infiltrating population present at the leading edge of mouse and human tumors that is enriched for axon guidance genes. High-throughput,in vivoscreening of these genes identified Sema4F as a key regulator of tumorigenesis and activity-dependent infiltration. Furthermore, Sema4F promotes the activity-dependent infiltrating population and propagates bi-directional signaling with neurons by remodeling tumor adjacent synapses towards brain network hyperactivity. Collectively, our studies demonstrate that subsets of neurons in locations remote to primary GBM promote malignant progression, while revealing new mechanisms of tumor infiltration that are regulated by neuronal activity.