bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hammerhead-type FXR agonists induce an eRNA FincoR that ameliorates nonalcoholic steatohepatitis in mice
Authors: Chen Jinjing , Wang Ruoyu , Xiong Feng , Sun Hao , Kemper Byron , Li Wenbo , Kemper Jongsook Kim 
Published: November 2023

AbstractThe nuclear receptor, Farnesoid X Receptor (FXR/NR1H4), is increasingly recognized as a promising drug target for metabolic diseases, including nonalcoholic steatohepatitis (NASH). Protein coding genes regulated by FXR are well known, but whether FXR also acts through regulation of long non-coding RNAs (lncRNAs), which vastly outnumber protein-coding genes, remains unknown. Utilizing RNA-seq and GRO-seq analyses in mouse liver, we found that FXR activation affects the expression of many RNA transcripts from chromatin regions bearing enhancer features. Among these we discovered a previously unannotated liver-enriched enhancer-derived lncRNA (eRNA), termedFincoR. We show thatFincoRis specifically induced by the hammerhead-type FXR agonists, including GW4064 and tropifexor. CRISPR/Cas9-mediated liver-specific knockdown ofFincoRin dietary NASH mice reduced the beneficial effects of tropifexor, an FXR agonist currently in clinical trials for NASH and primary biliary cholangitis (PBC), indicating that that amelioration of liver fibrosis and inflammation in NASH treatment by tropifexor is mediated in part byFincoR. Overall, our findings highlight that pharmacological activation of FXR by hammerhead-type agonists induces a novel eRNA,FincoR, contributing to the amelioration of NASH in mice.FincoRmay represent a new drug target for addressing metabolic disorders, including NASH.
Quantitative cell morphology inC. elegansembryos reveals regulations of cell volume asymmetry
Authors: Guan Guoye , Li Zelin , Ma Yiming , Cao Jianfeng , Wong Ming-Kin , Chan Lu-Yan , Yan Hong , Tang Chao , Zhao Zhongying 
Published: November 2023

ABSTRACTThe dynamics of cellular morphology throughout development are crucial for morphogenesis and organogenesis, yet their systematic characterization remains a significant challenge. By integrating both nuclear position and advanced cell membrane labeling, we develop a novel method that enables the segmentation of surfaces for over 95% of cells produced duringCaenorhabditis elegansembryogenesis. With this method, we segment eight wild-type and four perturbed embryos. The output, including cell identity, shape, volume, surface and contact area, can be visualized using our custom software. We demonstrate that signaling interactions, such as Notch and Wnt, regulate not only the asymmetry of cell fate but also the asymmetry of cell volume in conjunction with mechanical compression. Furthermore, we find that the asymmetries of fate and volume are generally interconnected.ONE SENTENCE SUMMARYSystematic quantification of cell morphology with resolved cell lineage and cell fate in developingC. elegansembryo uncovers multimodal regulations of cell size.Potential Cover/Featured Image: Smiling “ghost” face ofC. elegansembryo.Center: shown are skins (colored in red, dorsal view with anterior to the bottom) of a 400-celledC. elegansembryo. Cells not covered by the skins are colored in gray, green, blue, and transparent yellow, respectively. Internal and external circles: confocal fluorescence images (GFP for cell nucleus and mCherry for cell membrane) and reconstructed cell morphologies of theC. elegansembryo from the 2- to 550-cell stages respectively, connected with images of aC. elegansadult expressing the same markers.
Plastic vasomotion entrainment
Authors: Sasaki Daichi , Imai Ken , Ikoma Yoko , Matsui Ko 
Published: November 2023

AbstractThe presence of global synchronization of vasomotion induced by oscillating visual stimuli was identified in the mouse brain. Endogenous autofluorescence was used and the vessel “shadow” was quantified to evaluate the magnitude of the frequency-locked vasomotion. This method allows vasomotion to be easily quantified in non-transgenic wild-type mice using either the wide-field macro-zoom microscopy or the deep-brain fiber photometry methods. Vertical stripes horizontally oscillating at a low temporal frequency (0.25 Hz) were presented to the awake mouse and oscillatory vasomotion locked to the temporal frequency of the visual stimulation was induced not only in the primary visual cortex but across a wide surface area of the cortex and the cerebellum. The visually induced vasomotion adapted to a wide range of stimulation parameters. Repeated trials of the visual stimulus presentations resulted in the entrainment of the amplitude of the vasomotion. Horizontally oscillating visual stimulus is known to induce horizontal optokinetic response (HOKR). The amplitude of the eye movement is known to increase with repeated training sessions and the flocculus region of the cerebellum is known to be essential for this learning to occur. Here, we show a strong correlation between the average HOKR performance gain and the vasomotion entrainment magnitude in the cerebellar flocculus. Therefore, the plasticity of vasomotion and neuronal circuits appeared to occur in parallel. Efficient energy delivery by the entrained vasomotion may contribute to meeting the energy demand for increased coordinated neuronal activity and the subsequent neuronal circuit reorganization.
Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations
Authors: Alqazzaz Mona A. , Luciani Genna M. , Vu Victoria , Machado Raquel Martinez , Szewczyk Magdalena M. , Adamson Ella C. , Cheon Sehyun , Li Fengling , Arrowsmith Cheryl H. , Minden Mark D. , Barsyte-Lovejoy Dalia 
Published: November 2023

AbstractEpigenetic regulators such as the polycomb repressive complex 2 (PRC2) play a critical role in both normal development and carcinogenesis. Mutations and functional dysregulation of PRC2 complex components such as EZH2 are implicated in various forms of cancer and associated with poor prognosis. This study investigated the epigenetic vulnerabilities of acute myeloid leukemia (AML) and myelodysplastic/myeloproliferative disorders (MDS/MPN) by performing a chemical probe screen in patient cells. Paradoxically, we observed increased sensitivity to EZH2 and EED inhibitors in AML and MDS/MPN patient cells harboringEZH2mutations. Expression analysis indicated that EZH2 inhibition elicited upregulation of pathways responsible for cell death and growth arrest, specifically in patient cells with mutant EZH2. The identifiedEZH2mutations had drastically reduced catalytic activity, resulting in lower cellular H3K27me3 levels and were associated with decreased EZH2 and PRC2 component EED protein levels. Overall, this study provides an important understanding of the role of EZH2 dysregulation in blood cancers and may indicate disease etiology for these poor prognosis AML and MDS/MPN cases.
A UHPLC–MS/MS method for determination of N-acylethanolamines in cerebrospinal fluid
Authors: Ismoilova Visolakhon , Wretlind Asger , Hooshmand Kourosh , Simonsen Anja Hviid , Hasselbalch Steen Gregers , Quigley Cristina Legido 
Published: November 2023

AbstractN-acylethanolamines (NAEs) and primary fatty amides (PFAMs) are of a great interest due to the range of physiological effects they exhibit, potentially serving as neuromodulators. However, they are present at nano and picomolar concentrations in human cerebrospinal fluid (CSF) samples, posing challenges for detection and measurement using conventional Ultra-high performance liquid chromatography systems coupled to tandem mass spectrometry (UHPLC-MS).UHPLC-MS was used in dynamic multiple reaction monitoring (dMRM) mode. Seven deuterated NAEs internal standards were used to develop the method. Six solvent combinations were tested for extraction efficiency, accuracy, precision, matrix effect, linearity, limits of detection. Lastly the method was applied to CSF from healthy individuals (n=33) to estimate their natural range of concentrations.Extraction with acetonitrile/acetone showed the highest efficiency and recovery. The presented method was able to measure the following 17 NAEs and PFAMs in human CSF: linoleoyl ethanolamide, heptadecanoyl ethanolamide, stearoyl ethanolamide, palmitoyl ethanolamide, dihomolinolenoyl ethanolamide, eicosatrienoic acid ethanolamide, behenamide, octadecanamide, lauramide, tetradecanamide, erucamide, linoleamide, palmitamide, myristic monoethanolamide, pentadecanoyl ethanolamide, oleamide and palmitoleoyl ethanolamide. In healthy individuals the concentrations ranged three-fold from pg/mL to mg/mL. Further studies could apply this method to clinical CSF samples.
Dollo parsimony overestimates ancestral gene content reconstructions
Authors: Gàlvez-Morante Alex , Guéguen Laurent , Natsidis Paschalis , Telford Maximilian J. , Richter Daniel J. 
Published: November 2023

AbstractAncestral reconstruction is a widely-used technique that has been applied to understand the history of gain and loss of gene families over evolutionary time scales, and to produce hypotheses on how these gains and losses may have influenced the evolutionary trajectories of extant organisms.Ancestral gene content can be reconstructed via different phylogenetic methods, such as maximum likelihood or Bayesian inference, but many current and previous studies employ Dollo parsimony. We hypothesize that Dollo parsimony is not appropriate for ancestral gene content reconstruction inferences based on sequence homology, as Dollo parsimony is derived from the assumption that a complex character can only be gained once in evolutionary history. This premise does not accurately model molecular sequence evolution, in which false orthology can result from sequence convergence (including random sequence similarity and parallel gene gains), non-orthologous homology or lateral gene transfer. The aim of this study is to test Dollo parsimony’s suitability for ancestral gene content reconstruction and to compare its inferences with a maximum likelihood-based approach which allows a gene family to be gained more than once within a tree.In order to test our hypothesis, we first compared the performance of the two approaches on a series of artificial datasets each of 5,000 genes that were simulated according to a spectrum of evolutionary rates. Next, we reconstructed protein domain evolution on a phylogeny representing known eukaryotic diversity. We observed that Dollo parsimony produced numerous ancestral gene content overestimations, which were more pronounced at nodes closer to the root of the tree. These observations led us to the conclusion that, confirming our hypothesis, Dollo parsimony is not an appropriate method for ancestral reconstruction studies based on sequence homology.
Spatiotemporal analysis of gene expression in the human dentate gyrus reveals age-associated changes in cellular maturation and neuroinflammation
Authors: Ramnauth Anthony D. , Tippani Madhavi , Divecha Heena R. , Papariello Alexis R. , Miller Ryan A. , Nelson Erik D. , Pattie Elizabeth A. , Kleinman Joel E. , Maynard Kristen R. , Collado-Torres Leonardo , Hyde Thomas M. , Martinowich Keri , Hicks Stephanie C. , Page Stephanie C. 
Published: November 2023

AbstractThe dentate gyrus of the hippocampus is important for many cognitive functions, including learning, memory, and mood. Here, we investigated age-associated changes in transcriptome-wide spatial gene expression in the human dentate gyrus across the lifespan. Genes associated with neurogenesis and the extracellular matrix were enriched in infants, while gene markers of inhibitory neurons and cell proliferation showed increases and decreases in post-infancy, respectively. While we did not find evidence for neural proliferation post-infancy, we did identify molecular signatures supporting protracted maturation of granule cells. We also identified a wide-spread hippocampal aging signature and an age-associated increase in genes related to neuroinflammation. Our findings suggest major changes to the putative neurogenic niche after infancy and identify molecular foci of brain aging in glial and neuropil enriched tissue.
Multiple focal pulvinar projection fields in the macaque cortex
Authors: Froesel Mathilda , Clavagnier Simon , Goudard Quentin , Zhu Qi , Vanduffel Wim , Ben Hamed Suliann 
Published: November 2023

AbstractThe pulvinar, the largest nucleus of the thalamus, is functionally heterogeneous and involved in multiple cognitive functions. It has been proposed to act as a functional hub of cortical processes due to its extensive reciprocal connectivity with the cortex. However, its role in cognition is not fully understood yet. Here, we posit that an improved understanding of its functional connectivity with the cortex is needed to better capture the cognitive functions of this nucleus. To address this question, we characterize the pulvino-cortical functional connectivity along the ventro-dorsal, antero-posterior and medio-lateral axes, using awake resting state data from ten adult macaques. We first report two global cortical functional connectivity gradients along the antero-posterior and ventro-dorsal pulvinar gradients, that match remarkably well the structural connectivity gradients described by anatomical approaches. In addition to these global gradients, multiple local cortical pulvinar projection fields can be identified at the sulci level such as in the lateral sulcus (LS), the intraparietal sulcus (IPS), the principal sulci (PS) and the anterior cingulate cortex (ACC). For most sulci, we show that functional pulvino-cortical projection fields follow the major anatomical axis of these different sulci (e.g. the ventro-dorsal axis for the LS and the antero-posterior axis for the IPS). Other sulci, such as the superior temporal sulcus, the posterior cingulate cortex or the central sulcus, display multiple projection fields from the pulvinar. Although substantial inter-individual differences exist, the general functional connectivity patterns are remarkably consistent across hemispheres and individuals. Overall, we propose that these multiple pulvinar projection fields correspond to a fundamental principle of pulvino-cortical connectivity and that a better understanding of this connectional organization will shed light on the function of pulvino-cortical interactions and the role of the pulvinar in cognition at large.
Refinement of the “CandidatusAccumulibacter” Genus Based on a Metagenomic Analysis of Biological Nutrient Removal (BNR) Pilot-Scale Plants Operated with Reduced Aeration
Authors: Stewart Rachel D. , Myers Kevin S. , Amstadt Carly , Seib Matt , McMahon Katherine D. , Noguera Daniel R. 
Published: November 2023

ABSTRACTMembers of the “CandidatusAccumulibacter” genus are widely studied as key polyphosphate-accumulating organisms (PAOs) in biological nutrient removal (BNR) facilities performing enhanced biological phosphorus removal (EBPR). This diverse lineage includes 18 “Ca. Accumulibacter” species, which have been proposed based on the phylogenetic divergence of the polyphosphate kinase 1 (ppk1) gene and genome-scale comparisons of metagenome-assembled genomes (MAGs). Phylogenetic classification based on the 16S rRNA genetic marker has been difficult to attain because most “Ca. Accumulibacter” MAGs are incomplete and often do not include the rRNA operon. Here, we investigate the “Ca. Accumulibacter” diversity in pilot-scale treatment trains performing BNR under low dissolved oxygen (DO) conditions using genome-resolved metagenomics. Using long-read sequencing, we recovered medium and high-quality MAGs for 5 of the 18 “Ca. Accumulibacter” species, all with rRNA operons assembled, which allowed a reassessment of the 16S rRNA-based phylogeny of this genus and an analysis of phylogeny based on the 23S rRNA gene. In addition, we recovered a cluster of MAGs that based on 16S rRNA, 23S rRNA,ppk1, and genome-scale phylogenetic analyses do not belong to any of the currently recognized “Ca. Accumulibacter” species for which we propose the new species designation “Ca. Accumulibacter jenkinsii” sp. nov. Relative abundance evaluations of the genus across all pilot plant operations revealed that regardless of the operational mode, “Ca. A. necessarius” and “Ca. A. propinquus” accounted for more than 40% of the “Ca. Accumulibacter” community, whereas the newly proposed “Ca. A. jenkinsii” accounted for about 5% of the “Ca. Accumulibacter” community.IMPORTANCEOne of the main drivers of energy use and operational costs in activated sludge processes is the amount of oxygen provided to enable biological phosphorus and nitrogen removal. Wastewater treatment facilities are increasingly considering reduced aeration to decrease energy consumption, and whereas successful BNR has been demonstrated in systems with minimal aeration, an adequate understanding of the microbial communities that facilitate nutrient removal under these conditions is still lacking. In this study, we used genome-resolved metagenomics to evaluate the diversity of the “CandidatusAccumulibacter” genus in pilot-scale plants operating with minimal aeration. We identified the “Ca.Accumulibacter” species enriched under these conditions, including one novel species for which we propose “Ca.Accumulibacter jenkinsii” sp. nov. as its designation. Furthermore, the MAGs obtained for 5 additional “Ca.Accumulibacter” species further refine the phylogeny of the “Ca.Accumulibacter” genus and provide new insight into its diversity within unconventional biological nutrient removal systems.
Characteristics of putative keystones in the healthy adult human gut microbiome as determined by correlation network analysis
Authors: Bauchinger Franziska , Seki David , Berry David 
Published: November 2023

ABSTRACTKeystone species are thought to play a critical role in determining the structure and function of microbial communities. As they are important candidates for microbiome-targeted interventions, the identification and characterization of keystones is a pressing research goal. Both empirical as well as computational approaches to identify keystones have been proposed, and in particular correlation network analysis is frequently utilized to interrogate sequencing-based microbiome data. Here, we apply an established method for identifying putative keystone taxa in correlation networks. We develop a robust workflow for network construction and systematically evaluate the effects of taxonomic resolution on network properties and the identification of keystone taxa. We are able to identify correlation network keystone species and genera, but could not detect taxa with high keystone potential at lower taxonomic resolution. Based on the correlation patterns observed, we hypothesize that the identified putative keystone taxa have a stabilizing effect that is exerted on correlated taxa. Correlation network analysis further revealed subcommunities present in the dataset that are remarkably similar to previously described patterns. The interrogation of available metatranscriptomes also revealed distinct transcriptional states present in all putative keystone taxa.IMPORTANCEThe work presented here contributes to the understanding of correlation network keystone taxa and sheds light on their potential ecological significance. By employing a robust workflow based on bootstrapping and subsampling techniques, we identify putative keystone species at the genus and species level. This emphasizes the importance of considering taxonomic resolution when investigating correlations. The potential impact of keystones on community stability provides valuable insights for systematic microbiome manipulation. Furthermore, the observed clusters of co-occurring taxa align well with recent findings and emphasize the reproducibility and relevance of the identified patterns in microbial community composition. We are able to add a functional dimension to the analysis with the identification of distinct transcriptional states in putative keystone taxa, highlighting their functional versatility and adaptability.
Microeukaryote metabolism across the western North Atlantic Ocean revealed through autonomous underwater profiling
Authors: Cohen Natalie R. , Krinos Arianna I. , Kell Riss M. , Chmiel Rebecca J. , Moran Dawn M. , McIlvin Matthew R. , Lopez Paloma Z. , Barth Alexander , Stone Joshua , Alanis Brianna A. , Chan Eric W. , Breier John A. , Jakuba Michael V. , Johnson Rod , Alexander Harriet , Saito Mak A. 
Published: November 2023

AbstractProtists (microeukaryotes) are key contributors to marine carbon cycling, influencing the transfer of energy to higher trophic levels and the vertical movement of carbon to the ocean interior. Their physiology, ecology, and interactions with the chemical environment are still poorly understood in offshore ecosystems, and especially in the deep ocean. Using the Autonomous Underwater Vehicle (AUV)Clio, the microbial community along a 1,050 km transect in the western North Atlantic Ocean was surveyed at 10-200 m vertical depth increments to capture metabolic microeukaryote signatures spanning a gradient of oligotrophic, continental margin, and productive coastal ecosystems. Plankton biomass was collected along the surface of this transect and across depth features, and taxonomy and metabolic function were examined using a paired metatranscriptomic and metaproteomic approach. A shift in the microeukaryote community composition was observed from the euphotic zone through the mesopelagic and into the bathypelagic ocean. A diverse surface assemblage consisting of haptophytes, stramenopiles, dinoflagellates and ciliates was represented in both the transcript and protein fractions, with foraminifera, radiolaria, picozoa, and discoba proteins enriched at >200 m depth, and fungal proteins emerging in waters >3,000 m depth. In the broad microeukaryote community, nitrogen stress biomarkers were found in productive coastal sites, with phosphorus stress biomarkers in offshore waters where Saharan dust input is thought to supply iron and nitrogen. This multi-omics dataset broadens our understanding of how microeukaryotic taxa and their functional processes are structured along environmental gradients of temperature, light, macronutrients, and trace metals.