bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide methylome stability and parental effects in the worldwide distributed Lombardy poplar
Authors: Broeck An Vanden , Meese Tim , Verschelde Pieter , Cox Karen , Heinze Berthold , Deforce Dieter , Meester Ellen De , Nieuwerburgh Filip Van 
Published: March 2023

AbstractBackgroundDespite the increasing number of epigenomic studies in plants, little is known about the forces that shape the methylome in long-lived woody perennials. The Lombardy poplar offers an ideal opportunity to investigate the impact of the individual environmental history of trees on the methylome.ResultsWe present the results of three interconnected experiments on Lombardy poplar. In the first experiment, we investigated methylome variability during a growing season and across vegetatively reproduced generations. We found that ramets collected over Europe and raised in common conditions have stable methylomes in symmetrical CG-contexts. In contrast, seasonal dynamics occurred in methylation patterns in CHH-context. In the second experiment, we investigated whether methylome patterns of plants grown in a non-parental environment correlate with the parental climate. We did not observe a biological relevant pattern that significantly correlates with the parental climate. Finally, we investigated whether the parental environment has persistent carry-over effects on the vegetative offsprings’ phenotype. We combined new bud set observations of three consecutive growing seasons with former published bud set data. Using a linear mixed effects analysis, we found a statistically significant but weak short-term, parental carry-over effect on the timing of bud set. However, this effect was negligible compared to the direct effects of the offspring environment.ConclusionsGenome-wide cytosine methylation patterns in symmetrical CG-context are stable in Lombardy poplar and appear to be mainly the result of random processes. In this widespread poplar clone, methylation patterns in CG-context can be used as bio-markers to infer a common ancestor and thus to investigate the recent environmental history of a specific Lombardy poplar. The Lombardy poplar shows high phenotypic plasticity in a novel environment which enabled this clonal tree to adapt and survive all over the temperate regions of the world.
Swimming, Feeding and Inversion of Multicellular Choanoflagellate Sheets
Authors: Fung Lloyd , Konkol Adam , Ishikawa Takuji , Larson Ben T. , Brunet Thibaut , Goldstein Raymond E. 
Published: March 2023

AbstractThe recent discovery of the striking sheet-like multicellular choanoflagellate speciesChoanoeca flexathat dynamically interconverts between two hemispherical forms of opposite orientation raises fundamental questions in cell and evolutionary biology, as choanoflagellates are the closest living relatives of animals. It similarly motivates questions in fluid and solid mechanics concerning the differential swimming speeds in the two states and the mechanism of curvature inversion triggered by changes in the geometry of microvilli emanating from each cell. Here we develop fluid dynamical and mechanical models to address these observations and show that they capture the main features of the swimming, feeding, and inversion ofC. flexacolonies.
Using a handful of transcriptomes to detect sex-linked markers in a lizard with homomorphic sex chromosomes
Authors: Saunders Paul A. , Ferre-Ortega Carles , Hill Peta , Simakov Oleg , Ezaz Tariq , Burridge Christopher P. , Wapstra Erik 
Published: March 2023

AbstractTo understand the biology of a species it is often crucial to be able to differentiate males and females. Many species lack distinguishable sexually dimorphic traits, but in those that possess sex chromosomes, molecular sexing offers a good alternative. Designing molecular sexing assays is typically achieved through the comparison of male and female genomic sequences, often from reduced-representation sequencing. However, in many non-model species sex chromosomes are poorly differentiated, and identifying sex-limited sequences and developing PCR-based sexing assays is challenging without additional genomic resources. Here we highlight a simple procedure for detection of sex-linked markers based on transcriptomes that circumvents limitations of other approaches. We apply it to the spotted snow skinkCarinascincus ocellatus, a lizard with homomorphic XY chromosomes that also experiences environmentally-induced sex reversal. With transcriptomes from 3 males and 3 females alone, we identify thousands of putative Y-linked sequences. We confirm linkage through alignment of assembled transcripts to a distantly related genome, and readily design PCR primers to sexC. ocellatusand related species. In addition to providing an important molecular sexing tool for these species, this approach also facilitated valuable comparisons of sex determining systems on a large taxonomic scale.
FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress
Authors: Dai Wenting , Wang Zhichao , Wang Guan , Wang Qiong A. , DeBerardinis Ralph , Jiang Lei 
Published: March 2023

SummaryFatty acid synthase (FASN) maintainsde novolipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-CoA is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation under hypoxia. Here we show that reductive carboxylation also occurs in the absence of DNL in cells with defective FASN. In this state, reductive carboxylation was mainly catalyzed by isocitrate dehydrogenase-1 (IDH1) in the cytosol, but IDH1-generated citrate was not used for DNL. Metabolic flux analysis (MFA) revealed that FASN-deficiency induced a net cytosol-to-mitochondria citrate flux through citrate transport protein (CTP). A similar pathway was previously shown to mitigate detachment-induced mitochondrial reactive oxygen species (mtROS) in anchorage-independent tumor spheroids. We further demonstrate that FASN-deficient cells acquire resistance to oxidative stress in a CTP- and IDH1-dependent manner. Together with the reduced FASN activity in tumor spheroids, these data indicate that anchorage-independent malignant cells trade FASN-supported rapid growth for a cytosol-to-mitochondria citrate flux to gain redox capacity against detachment-induced oxidative stress.
RAPD amplicon sequence based metagenomics analysis of microbial communities associated with clove (Syzygium aromaticum) from Kerala, India
Authors: Santhakumari Sreekala Gangappan , Santhosh Ramachandran Sarojini 
Published: March 2023

AbstractFour clove clones (BRC1, BRC3 MRC5 and MRC7) were collected from different places of ponmudi hills, Kerala, India. DNA was extracted and RAPD analysis was designed to evaluate clove clonal variation. Upon analysis bacterial sequences were also identified among clove genome sequences. So the clove and microbial sequences were separated and performed an analysis to identify clove associated metagenome. The major microbes present wereMycobacterium canettii Xanthomaonas euvesicateria, KlebsiellaandPsuedomonas. A total of 88 genus of microbes were present altogether in four clones ofSyzygium aromaticum. There were few fungal species were also identified,Fusarium pseudograminearumwas the major fungus associated with all four different clones of clove.
Single-cell expression predicts neuron specific protein homeostasis networks
Authors: Pechmann Sebastian 
Published: March 2023

ABSTRACTThe protein homeostasis network keeps proteins in their correct shapes and avoids unwanted protein aggregation. In turn, the accumulation of aberrantly misfolded proteins has been directly associated with the onset of aging-associated neurodegenerative diseases such as Alzheimer’s and Parkinson’s. However, a detailed and rational understanding of how protein homeostasis is achieved in health, and how it can be targeted for therapeutic intervention in diseases remains missing. Here, large-scale single-cell expression data from the Allen Brain Map is analyzed to investigate the transcription regulation of the core protein homeostasis network across the human brain. Remarkably, distinct expression profiles suggest specialized protein homeostasis networks with systematic adaptations in excitatory neurons, inhibitory neurons, and non-neuronal cells. Moreover, several chaperones and Ubiquitin ligases are found transcriptionally coregulated with genes important for synapse formation and maintenance, thus linking protein homeostasis to the regulation of neuronal function. Finally, evolutionary analyses highlight the conservation of an elevated interaction density in the chaperone network, suggesting that one of the most exciting aspects of chaperone action may yet be discovered in their collective action at the systems level. More generally, our work highlights the power of computational analyses for breaking down complexity and gaining complementary insights into fundamental biological problems.
The impact of paramutations on the invasion dynamics of transposable elements
Authors: Scarpa Almorò , Kofler Robert 
Published: March 2023

AbstractAccording to the prevailing view, the trap model, invading transposable elements (TEs) are stopped in their proliferation when a TE copy jumps into a piRNA cluster, which triggers the emergence of piRNAs that silence the TE. One crucial component in the host defence are paramutations. Mediated by maternally deposited piRNAs, paramutations convert TE insertions into piRNA producing loci, thereby transforming selfish TEs into agents of the host defence. Despite this significant effect, the impact of paramutations on the dynamics of TE invasions remains unknown. To address this issue, we performed extensive forward simulations of TE invasions with piRNA clusters and paramutations. We found that paramutations significantly affect TE dynamics, by accelerating the silencing of TE invasions, reducing the number of insertions accumulating during the invasions and mitigating the fitness cost of TEs. We also demonstrate that piRNA production induced by paramutations, an epigenetically inherited trait, may be positively selected. Finally, we show that paramutations may account for three important open problems with the trap model. Firstly, paramutated TE insertions may compensate for the insufficient number of insertions in piRNA clusters observed in previous studies. Secondly, paramutations may explain the discrepancy between the observed and the expected abundance of different TE families inD. melanogaster. Thirdly, paramutations render piRNA clusters dispensable once the host defence has been established, which may account for the lack of TE activation when three major piRNA clusters were deleted in a previous study.
Nocturnal increase in cerebrospinal fluid secretion as a regulator of intracranial pressure
Authors: Steffensen Annette Buur , Edelbo Beatriche Louise , Barbuskaite Dagne , Andreassen Søren Norge , Olsen Markus Harboe , Møller Kirsten , MacAulay Nanna 
Published: March 2023

ABSTRACTIt is crucial to maintain the intracranial pressure (ICP) within the physiological range to ensure proper brain function. The ICP may fluctuate during the light-dark phase cycle, complicating diagnosis and treatment choice in patients with pressure-related disorders. Such ICP fluctuations may originate in circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which in addition could support diurnal regulation of brain waste clearance. Through a combination of patient data andin vivotelemetric pressure measurements in adult male rats, we demonstrated that ICP increases in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients and CSF production rate in rats, the latter obtained with the ventriculo-cisternal perfusion assay. The dark-phase increase in CSF secretion in rats was, in part, assigned to increased transport activity of the choroid plexus Na+,K+,2Cl-cotransporter (NKCC1), which is implicated in CSF secretion by this tissue. In conclusion, CSF secretion, and thus ICP, increases in the dark phase in humans and rats, irrespective of their diurnal/nocturnal activity preference, in part due to altered choroid plexus transport activity. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself.
Mapping the landscape of magnetic field effects on neural regeneration and repair: a systematic review, mathematical model, and meta-analysis
Authors: McGraw Meghan , Gilmer Gabrielle , Bergmann Juliana , Seshan Vishnu , Wang Kai , Pekker David , Modo Michel , Ambrosio Fabrisia 
Published: March 2023

AbstractAlthough magnetic field exposure is a well-established diagnostic tool, its use as a therapeutic in regenerative medicine is relatively new. Our goal here was to evaluate how magnetic fields affect neural repairin vitroby performing a systematic review of the literature, mathematical modeling, and meta-analyses. The 38 included articles presented with high heterogeneity, representing 13 cell types, magnitudes ranging from 0.0002-10,000 mT, frequencies from 0-150 Hz, and exposure times lasting from one hour to several weeks. Mathematical modeling revealed that increasing magnetic field magnitude increases neural progenitor cell (NPC) viability. For regenerative processes that were not influenced by magnitude, frequency, and time, we integrated data with meta-analyses. Results revealed that magnetic field exposure increases NPC proliferation while decreasing astrocytic differentiation. Collectively, our work identifies neural repair processes that may be most responsive to magnetic field exposure and provides a framework for novel hypothesis and technology development.
Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygousHNF1B-associated dysplastic kidney malformations
Authors: Bantounas Ioannis , Rooney Kirsty M. , Lopes Filipa M. , Tengku Faris , Woods Steven , Zeef Leo A. H. , Kuba Shweta Y. , Bates Nicola , Hummelgaard Sandra , Hillman Katherine A , Cereghini Silvia , Woolf Adrian S. , Kimber Susan J. 
Published: March 2023

ABSTRACTHepatocyte nuclear factor 1B(HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. HeterozygousHNF1Bmutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygousHNF1Bmutant kidney organoids from CRISPR-Cas9 gene-edited human ESCs and iPSCs reprogrammed from a family withHNF1B-asscociated DKMs. Mutant organoids contained enlarged malformed tubules and displayed deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cAMP-mediated dilatation seen in controls. Bioinformatic analyses indicated abnormal WNT, calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 was upregulated in mutant organoids and was detected in their tubules and in fetal human DKM dysplastic epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule morphogenesis and functional differentiation. They additionally suggest druggable targets to ameliorate disease.
Leveraging gene correlations in single cell transcriptomic data
Authors: Silkwood Kai , Dollinger Emmanuel , Gervin Josh , Atwood Scott , Nie Qing , Lander Arthur D. 
Published: March 2023

AbstractBACKGROUNDMany approaches have been developed to overcome technical noise in single cell RNA-sequencing (scRNAseq). As researchers dig deeper into data—looking for rare cell types, subtleties of cell states, and details of gene regulatory networks—there is a growing need for algorithms with controllable accuracy and fewerad hocparameters and thresholds. Impeding this goal is the fact that an appropriate null distribution for scRNAseq cannot simply be extracted from data when ground truth about biological variation is unknown (i.e., usually).RESULTSWe approach this problem analytically, assuming that scRNAseq data reflect only cell heterogeneity (what we seek to characterize), transcriptional noise (temporal fluctuations randomly distributed across cells), and sampling error (i.e., Poisson noise). We analyze scRNAseq data without normalization—a step that skews distributions, particularly for sparse data—and calculatep-values associated with key statistics. We develop an improved method for selecting features for cell clustering and identifying gene-gene correlations, both positive and negative. Using simulated data, we show that this method, which we call BigSur (Basic Informatics andGeneStatistics fromUnnormalizedReads), captures even weak yet significant correlation structures in scRNAseq data. Applying BigSur to data from a clonal human melanoma cell line, we identify thousands of correlations that, when clustered without supervision into gene communities, align with known cellular components and biological processes, and highlight potentially novel cell biological relationships.CONCLUSIONSNew insights into functionally relevant gene regulatory networks can be obtained using a statistically grounded approach to the identification of gene-gene correlations.
Quorum Sensing Modulates Bacterial Virulence and Colonization Dynamics During an Enteric Infection
Authors: Peña-Díaz Jorge , Woodward Sarah E. , Creus-Cuadros Anna , Serapio-Palacios Antonio , Deng Wanyin , Finlay B. Brett 
Published: March 2023

AbstractQuorum Sensing (QS) is a form of cell-to-cell communication that enables bacteria to modify behaviour according to their population density. While QS has been proposed as a potential intervention against pathogen infection, QS-mediated communication within the mammalian digestive tract remains understudied. Using an LC-MS/MS approach, we discovered thatCitrobacter rodentium, a natural murine pathogen used to model human infection by pathogenicEscherichia coli, utilizes the CroIR system to produce three QS-molecules. We then profiled their accumulation bothin vitroand across different gastrointestinal sites over the course of infection. Importantly, we found that in the absence of QS capabilities the virulence ofC. rodentiumis enhanced. This highlights the role of QS as an effective mechanism to regulate virulence according to the pathogen’s spatio-temporal context to optimize colonization and transmission success. These results also demonstrate that inhibiting QS may not always be an effective strategy for the control of virulence.
GenoPipe: identifying the genotype of origin within (epi)genomic datasets
Authors: Lang Olivia , Srivastava Divyanshi , Pugh B. Franklin , Lai William KM 
Published: March 2023

ABSTRACTConfidence in experimental results is critical for discovery. As the scale of data generation in genomics has grown exponentially, experimental error has likely kept pace despite the best efforts of many laboratories. Technical mistakes can and do occur at nearly every stage of a genomics assay (i.e., cell line contamination, reagent swapping, tube mislabelling, etc.) and are often difficult to identify post-execution. However, the DNA sequenced in genomic experiments contains certain markers (e.g., indels) encoded within and can often be ascertained forensically from experimental datasets. We developed the Genotype validation Pipeline (GenoPipe), a suite of heuristic tools that operate together directly on raw and aligned sequencing data from individual high-throughput sequencing experiments to characterize the underlying genome of the source material. We demonstrate how GenoPipe validates and rescues erroneously annotated experiments by identifying unique markers inherent to an organism’s genome (i.e., epitope insertions, gene deletions, and SNPs).
Merging integrated population models and individual-based models to project population dynamics of recolonizing species
Authors: Petracca Lisanne S. , Gardner Beth , Maletzke Benjamin T. , Converse Sarah J. 
Published: March 2023

ABSTRACTRecolonizing species exhibit unique population dynamics, namely dispersal to and colonization of new areas, that have important implications for management. A resulting challenge is how to simultaneously model demographic and movement processes so that recolonizing species can be accurately projected over time and space. Integrated population models (IPMs) have proven useful for making inference about population dynamics by integrating multiple data streams related to population states and demographic rates. However, traditional IPMs are not capable of representing complex dispersal and colonization processes, and the data requirements for building spatially explicit IPMs to do so are often prohibitive. Contrastingly, individual-based models (IBMs) have been developed to describe dispersal and colonization processes but do not traditionally integrate an estimation component, a major strength of IPMs. We introduce a framework for spatially explicit projection modeling that answers the challenge of how to project an expanding population using IPM-based parameter estimation while harnessing the movement modeling made possible by an IBM. Our model has two main components: [1] a Bayesian IPM-driven age- and state-structured population model that governs the population state process and estimation of demographic rates, and [2] an IBM-driven spatial model describing the dispersal of individuals and colonization of sites. We applied this model to estimate current and project future dynamics of gray wolves (Canis lupus) in Washington State, USA. We used data from 74 telemetered wolves and yearly pup and pack counts to parameterize the model, and then projected statewide dynamics over 50 years. Mean population growth was 1.29 (95% CRI 1.26-1.33) during initial recolonization from 2009-2020 and decreased to 1.03 (IQR 1.00-1.05) in the projection period (2021-2070). Our results suggest that gray wolves have a >99% probability of colonizing the last of Washington State’s three specified recovery regions by 2030, regardless of alternative assumptions about how dispersing wolves select new territories. The spatially explicit modeling framework developed here can be used to project the dynamics of any species for which spatial spread is an important driver of population dynamics.
A thermodynamic analysis of CLC transporter dimerization in lipid bilayers
Authors: Chadda Rahul , Lee Taeho , Sandal Priyanka , Mahoney-Kruszka Robyn , Robertson Janice L. 
Published: March 2023

ABSTRACTThe CLC-ec1 chloride/proton antiporter is a membrane embedded homodimer where subunits can dissociate and associate, but the thermodynamic driving forces favor the assembled form at biological densities. Yet, the physical reasons for this stability are confounding since binding occurs via the burial of hydrophobic protein interfaces yet the hydrophobic effect should not apply since there is little water within the membrane. To investigate this further, we quantified the thermodynamic changes associated with CLC dimerization in membranes by carrying out a van ′t Hoff analysis of the temperature dependency of the free energy of dimerization,ΔG°. To ensure that the reaction reached equilibrium under changing conditions, we utilized a Förster Resonance Energy Transfer based assay to report on the relaxation kinetics of subunit exchange as a function of temperature. These equilibration times were then applied to measure CLC-ec1 dimerization isotherms as a function of temperature using the single-molecule subunit-capture photobleaching analysis approach. The results demonstrate that the dimerization free energy of CLC inE. colimembranes exhibits a non-linear temperature dependency corresponding to a large, negative change in heat capacity, a signature of solvent ordering effects including the hydrophobic effect. Consolidating this with our previous molecular analyses suggests that the non-bilayer defect required to solvate the monomeric state is the molecular source of this large change in heat capacity and is a major and generalizable driving force for protein association in membranes.