bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perinatal High Fat Diet Exposure Alters Oxytocin and Corticotropin Releasing Factor Inputs onto Vagal Neurocircuits Controlling Gastric Motility
Authors: Carson Kaitlin E. , Alvarez Jared , Mackley Jasmine , Travagli R. Alberto , Browning Kirsteen N. 
Published: November 2022

AbstractPerinatal high fat diet (pHFD) exposure alters the development of vagal neurocircuits that control gastrointestinal (GI) motility and reduce stress resiliency in offspring. Descending oxytocin (OXT; prototypical anti-stress peptide) and corticotropin releasing factor (CRF; prototypical stress peptide) inputs from the paraventricular nucleus (PVN) of the hypothalamus to the dorsal motor nucleus of the vagus (DMV) modulate the GI stress response. How these descending inputs, and their associated changes to GI motility and stress responses, are altered following pHFD exposure are, however, unknown. The present study used retrograde neuronal tracing experiments,in vivorecordings of gastric tone, motility, and gastric emptying rates, andin vitroelectrophysiological recordings from brainstem slice preparations to investigate the hypothesis that pHFD alters descending PVN-DMV inputs and dysregulates vagal brain-gut responses to stress. Compared to controls, rats exposed to pHFD had slower gastric emptying rates and did not respond to acute stress with the expected delay in gastric emptying. Neuronal tracing experiments demonstrated that pHFD reduced the number of PVNOXTneurons that project to the DMV, but increased PVNCRFneurons. Bothin vitroelectrophysiology recordings of DMV neurons andin vivorecordings of gastric motility and tone demonstrated that, following pHFD, PVNCRF-DMV projections were tonically active, and that pharmacological antagonism of brainstem CRF1 receptors restored the appropriate gastric response to brainstem OXT application. These results suggest that pHFD exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress.Summary FigureKeypointsMaternal high fat diet exposure is associated with gastric dysregulation and stress sensitivity in offspringThe present study demonstrates that perinatal high fat diet exposure downregulates hypothalamic-vagal oxytocin (OXT) inputs but upregulates hypothalamic-vagal corticotropin releasing factor (CRF) inputsBoth in vitro and in vivo studies demonstrated that, following perinatal high fat diet, CRF receptors were tonically active at NTS-DMV synapses, and that pharmacological antagonism of these receptors restored appropriate gastric response to OXTThe current study suggests that perinatal high fat diet exposure disrupts descending PVN-DMV inputs, leading to a dysregulated vagal brain-gut response to stress.
Eosinophilic esophagitis-associated epithelial remodeling may limit esophageal carcinogenesis
Authors: Fuller Annie D. , Karami Adam L. , Kabir Mohammad Faujul , Klochkova Alena , Jackson Jazmyne L. , Mu Anbin , Tan Yinfei , Klein-Szanto Andres , Whelan Kelly A. 
Published: November 2022

AbstractUnder homeostatic conditions, esophageal epithelium displays a proliferation/differentiation gradient that is generated as proliferative basal cells give rise to suprabasal cells then terminally differentiated superficial cells. This proliferation/differentiation gradient is perturbed in esophageal pathologies both benign and malignant. Esophageal cancer is among the deadliest forms of human malignancy with 5-year survival rates of <20%. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two most common subtypes of esophageal cancer. Gastroesophageal reflux disease (GERD) is a primary risk factor for EAC. Although GERD and the food allergy-mediated condition eosinophilic esophagitis (EoE) are both associated with chronic esophageal inflammation and epithelial remodeling, including basal cell hyperplasia, epidemiological evidence suggests that EoE patients do not develop esophageal malignancy. Here, we perform single cell RNA-sequencing in murine models of EoE and ESCC to delineate the effects that these two conditions have specifically upon the cellular landscape of esophageal epithelium. In mice with EoE or ESCC, we find expansion of cell populations as compared to normal esophageal epithelium. In mice with EoE, we detect expansion of 4 suprabasal populations coupled with depletion of 4 basal cell populations. By contrast, mice with ESCC display expansion of 4 basal populations as well as depletion of 3 superficial populations. We further evaluated modules of co-expressed genes in EoE- and ESCC-enriched epithelial cell clusters. Senescence, glucocorticoid receptor signaling, and granulocyte-macrophage colony-stimulating factor pathways were associated with EoE-enriched clusters while pathways associated with cell proliferation and metabolism were identified in ESCC-enriched clusters. Finally, by pairing murine models of EoE and ESCC, we demonstrate that exposure to EoE inflammation limits esophageal carcinogenesis. Our findings provide the first functional investigation of the relationship between EoE and esophageal cancer and suggest that esophageal epithelial remodeling events occurring in response to EoE inflammation may limit act to esophageal carcinogenesis which may have future implications for leveraging allergic inflammation-associated alterations in epithelial biology to prevent and/or treat esophageal cancer.
Spontaneous confinement of mRNA at RNP granule interfaces
Authors: Perelman Rebecca T. , Schmidt Andreas , Khan Umar , Walter Nils G. 
Published: November 2022

AbstractCellular membraneless organelles termed ribonucleoprotein (RNP) granules often are enriched in messenger RNA (mRNA) molecules relative to the surrounding cytoplasm. Yet, the spatial localization and diffusion of mRNAs in close proximity to phase separated RNP granules is not well understood. In this study, we performed single molecule fluorescence imaging experiments of mRNAs in live cells in the presence of two types of RNP granules, stress granules (SG) and processing bodies (PB), which are distinct in their molecular composition and function. We developed a new colocalization imaging algorithm that was employed to determine the accurate positions of individual mRNAs relative to the granule’s boundaries. We found that mRNA is often localized at granule boundaries, an observation consistent with recently published data1,2. We suggest that mRNA molecules become spontaneously confined at the RNP granule boundary similar to the adsorption of polymer molecules at liquid-liquid interfaces, which is observed in various technological and biological processes.
Mitotic bookmarking redundancy by nuclear receptors mediates robust post-mitotic reactivation of the pluripotency network
Authors: Chervova Almira , Molliex Amandine , Baymaz H. Irem , Papadopoulou Thaleia , Mueller Florian , Hercul Eslande , Fournier David , Dubois Agnès , Gaiani Nicolas , Beli Petra , Festuccia Nicola , Navarro Pablo 
Published: November 2022

AbstractMitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate post-mitotic gene reactivation. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the significance and importance of their bookmarking function. Here, we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover an unexpected redundancy among members of the protein superfamily of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ES-RRB is essential for mouse pluripotency, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly the most rapidly and strongly reactivated ones. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially by nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
Macrophage and neutrophil heterogeneity at single-cell spatial resolution in inflammatory bowel disease
Authors: Garrido-Trigo Alba , Corraliza Ana M. , Veny Marisol , Dotti Isabella , Melon-Ardanaz Elisa , Rill Aina , Crowell Helena L. , Corbí Ángel , Gudiño Victoria , Esteller Miriam , Álvarez-Teubel Iris , Aguilar Daniel , Masamunt M Carme , Killingbeck Emily , Kim Youngmi , Leon Michael , Visvanathan Sudha , Marchese Domenica , Caratù Ginevra , Martin-Cardona Albert , Esteve Maria , Panés Julian , Ricart Elena , Mereu Elisabetta , Heyn Holger , Salas Azucena 
Published: November 2022

ABSTRACTUlcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory intestinal diseases that show a perplexing heterogeneity in manifestations and response to treatment. The molecular basis for this heterogeneity remains uncharacterized. We applied single-cell RNA sequencing and CosMx™ Spatial Molecular Imaging to human colon and found the highest diversity in cellular composition in the myeloid compartment of UC and CD patients. Besides resident macrophage subsets (M0 and M2), patients showed a variety of activated macrophages including classical (M1 CXCL5 and M1 ACOD1) and new inflammation-dependent alternative (IDA) macrophages. In addition, we captured intestinal neutrophils in three transcriptional states. Subepithelial IDA macrophages expressedNRG1, which promotes epithelial differentiation. In contrast,NRG1lowIDA macrophages were expanded within the submucosa and in granulomas, in proximity to abundant inflammatory fibroblasts, which we suggest may promote macrophage activation. We conclude that macrophages sense and respond to unique tissue microenvironments, potentially contributing to patient-to-patient heterogeneity.
Distinct Differences in Gene Expression Profiles in Early and Late Stage Rhodesiense HAT Individuals in Malawi
Authors: Nambala Peter , Mulindwa Julius , Noyes Harry , Namulondo Joyce , Nyangiri Oscar , Matovu Enock , MacLeod Annette , Musaya Janelisa 
Published: November 2022

AbstractT. b. rhodesienseis the causative agent of rhodesian Human African trypanosomiasis (r-HAT) in Malawi. Clinical presentation of r-HAT in Malawi varies between the different foci and differs from East African HAT clinical phenotypes. The purpose of this study was to gain more insights into the transcriptomic profiles of patients with early stage 1 and late stage 2 HAT disease in Malawi. Whole blood from individuals infected withT. b. rhodesiensewas used for RNA-Seq. Control samples were from healthy trypanosome negative individuals matched on sex, age range, and disease focus. Illumina sequence FASTQ reads were aligned to the GRCh38 release 84 human genome sequence using HiSat2 and differential analysis was done in R using the DESeq2 package. XGR, ExpressAnalyst and InnateDB algorithms were used for functional annotation and gene enrichment analysis of significant differentially expressed genes. RNA-seq was done on 25 healthy controls and 23 r-HAT case samples of which 3 case samples were excluded for downstream analysis as outliers. 4519 genes were significantly differentially expressed (p adjusted <0.05) in individuals with early stage 1 r-HAT disease (n = 12) and 1824 genes in individuals with late stage 2 r-HAT disease (n = 8). Enrichment of innate immune response genes through neutrophil activation was identified in individuals with both early and late stages of the disease. Additionally, lipid metabolism genes were enriched in late stage 2 disease. We further identified uniquely upregulated genes (log2 Fold Change 1.4 - 2.0) in stage 1 (ZNF354C) and stage 2 (TCN1 and MAGI3) blood. Our data brings new insight into the human transcriptome landscape duringT. b. rhodesienseinfection. We have further identified key biological pathways and transcripts during stage 1 and stage 2 r-HAT. Lastly, we have identified potential diagnostic biomarkers that may be used for staging of r-HAT disease.
Euphorbia yadgirensis sp. nov., (Euphorbiaceae) from Karnataka state, India
Authors: Sarojini Devi N , Raja Kullayiswamy K 
Published: November 2022

AbstractEuphorbia yadgirensisis a new species from the scrub forest of Royangole village, Yadgiri district of Karnataka, India is described and illustrated here. It belongs to the genusEuphorbia,subg.Chamaesyce,sect.Longistylaeand resemblesEuphorbia kadapensis. However, it differs in its decumbent habit (vs. erect), sympodial monochasium (vs. dichotomous), laciniate stipules (vs. scaly), sutures absent on capsule (vs. present).
Exploring the Neural Processes behind Narrative Engagement: An EEG Study
Authors: Dini Hossein , Simonetti Aline , Bruni Luis Emilio 
Published: November 2022

AbstractPast cognitive neuroscience studies using naturalistic stimuli have considered narratives holistically and focused on cognitive processes. In this study, we incorporated the narrative structure—the dramatic arc—as an object of investigation, to examine how engagement levels fluctuate across a narrative-aligned dramatic arc. We explored the possibility of predicting self-reported engagement ratings from neural activity and investigated the idiosyncratic effects of each phase of the dramatic arc on brain responses as well as the relationship between engagement and brain responses. We presented a movie excerpt following the six-phase narrative arc structure to female and male participants while collecting EEG signals. We then asked this group of participants to recall the excerpt, another group to segment the video based on the dramatic arc model, and a third to rate their engagement levels while watching the movie. The results showed that the self-reported engagement ratings followed the pattern of the narrative dramatic arc. Moreover, whilst EEG amplitude could not predict group-averaged engagement ratings, other features comprising dynamic inter-subject correlation, dynamic functional connectivity patterns and graph features were able to achieve this. Furthermore, neural activity in the last two phases of the dramatic arc significantly predicted engagement patterns. This study is the first to explore the cognitive processes behind the dramatic arc and its phases. By demonstrating how neural activity predicts self-reported engagement, which itself aligns with the narrative structure, this study provides insights on the interrelationships between narrative structure, neural responses, and viewer engagement.Significance statementDramatic narratives follow a complex structure termed as the narrative arc. Here, we addressed the complexity of this structure in order to explore brain responses during narrative cognition. We examined the link between the narrative arc and its six phases with self-reported engagement, and whether brain responses elicited by a narrative can predict engagement levels. Our results showed that the group-averaged engagement ratings followed the dramatic arc model. EEG features predicted group-averaged engagement patterns and also engagement levels in the last two phases. This is the first study to characterize the narrative dramatic arc phases at the neural level. It contributes to the fields of cognitive narratology and neuroscience by extending current knowledge on how the brain responds to narratives.
Genomic footprints of bottleneck in landlocked salmon population
Authors: Subramanian Sankar , Kumar Manoharan 
Published: November 2022

AbstractAt the end of the last ice age, several Atlantic salmon populations got caught up in the lakes and other small waterbodies of the Northern Hemisphere. Therefore, the pattern of evolution shaping the landlocked salmon populations is different from the other anadromous salmons, which migrate between the sea and rivers. According to the theories of population genetics, the effect of genetic drift is expected to be more pronounced in the former compared to the latter. Here we examined this using the whole genome data of landlocked and anadromous salmon populations of Norway. Our results showed a 50-80% reduction in the genomic heterozygosity in the landlocked compared to anadromous salmon populations. The number and total size of the runs of homozygosity (RoH) segments of landlocked salmons were 2 to 8-fold higher than those of their anadromous counterparts. We found the former had a higher ratio of nonsynonymous-to-synonymous diversities than the latter. The investigation also revealed a significant elevation of homozygous deleterious Single Nucleotide Variants (SNVs) in the landlocked salmon compared to the anadromous populations. All these results point to a significant reduction in the population size of the landlocked salmons, which might have started after the last glacial epoch. Previous studies on terrestrial vertebrates observed similar signatures of a bottleneck when the populations from Island and the mainland were compared. Since landlocked waterbody such as ponds and lakes are geographically analogous to Islands for fish populations, the findings of this study suggest the similarity in the patterns of evolution between the two.
Computational deconvolution of fifteen leukocyte subtypes from DNA methylation microarrays trained on flow cytometry data in the Health and Retirement Study
Authors: Heiss Jonathan A. , Bakulski Kelly M. , Thyagarajan Bharat , Crimmins Eileen M. , Faul Jessica D. , Fisher Jonah D. , Just Allan C. 
Published: November 2022

AbstractAdjusting for cell composition is critical in epigenome-wide association studies of whole blood samples. Using DNA methylation of whole blood samples (as opposed to purified cell types) and complete blood counts/flow cytometry data from 2530 participants in the Health and Retirement Study, we trained and tested a computational model that extends the number of estimated leukocyte subtypes to fifteen compared to established models with six or seven cell types. Our model, which can be applied to both Illumina 450k and EPIC microarrays, explained a larger proportion of the observed variance in whole blood DNA methylation levels than popular reference-based cell deconvolution approaches, and vastly reduced the number of false-positive findings in a reanalysis of an epigenome-wide association study of chronological age.
Transcriptional signals of dedifferentiation in human cancer
Authors: Kildisiute Gerda , Kalyva Maria , Elmentaite Rasa , van Dongen Stijn , Thevanesan Christine , Piapi Alice , Ambridge Kirsty , Prigmore Elena , Haniffa Muzlifah , Teichmann Sarah A. , Straathof Karin , Cortés-Ciriano Isidro , Behjati Sam , Young Matthew D. 
Published: November 2022

AbstractAs normal cells transform into cancers, their cell state changes (or “dedifferentiates”), which may drive cancer cells into a stem-like or more primordial, foetal or embryonic cell state. Here, we used single cell atlases to study dedifferentiation in transcriptional terms across a wide spectrum of adult and childhood cancers. At the level of the whole transcriptome, we find that adult cancers rarely return to an embryonic state, but rather that a foetal state is a near-universal feature of childhood cancers. We extend these bulk transcriptomic findings to a single cell resolution analysis of colorectal and liver cancers, confirming the lack of reversion to a primordial state in adult tumours and the retention of foetal signals in childhood cancers. Our findings provide a nuanced picture of dedifferentiation in these two groups of neoplasms, indicating cancer-specific rather than universal patterns of dedifferentiation pervade adult epithelial cancers.
Early but not late exercise training in mice exacerbates hepatic inflammation in early NAFLD
Authors: Kovynev Artemiy , Ying Zhixiong , Lambooij Joost , Guigas Bruno , Rensen Patrick C.N. , Schönke Milena 
Published: November 2022

AbstractExercise effectively prevents obesity-related disorders, but it is unclear whether the beneficial health effects of exercise are restricted to unique circadian windows. Therefore, we aimed to study whether timing of exercise training differentially modulates the development and progression of non-alcoholic fatty liver disease (NAFLD), a disease currently estimated to affect over two billion people worldwide. We endurance-trained high fat-high cholesterol-fed NAFLD-prone male APOE*3-Leiden.CETP mice five times per week for eight weeks either in the early (ZT13) or in the late (ZT22) active phase and assessed the NAFLD score (histology) and hepatic inflammation compared to sedentary mice. Exercise training prevented an increase in body fat mass and fasting plasma glucose as expected, but neither early nor late training affected liver triglyceride or cholesterol content compared to sedentary mice, likely due to a very early stage of hepatic steatosis. In line, hepatic expression of de novo lipogenesis genes (e.g., Fasn, Srebp1c) was similarly downregulated by early and late training. However, exercise had a distinct time-dependent effect on hepatic inflammation, as only early training promoted an influx of pro-inflammtory cells into the liver paired with increased expression of the pro-inflammatory cytokines (e.g. Tnfa, Il1b). This data suggests that the timing of exercise is a critical factor for the effect on cardiometabolic disease development.
Remodelled Ribosomes Synthesise a Specific Proteome in Proliferating Plant Tissue during Cold
Authors: Martinez-Seidel Federico , Suwanchaikasem Pipob , Gentry-Torfer Dione , Rajarathinam Yogeswari , Ebert Alina , Erban Alexander , Pereira Firmino Alexandre Augusto , Nie Shuai , Leeming Michael G. , Williamson Nicholas A. , Roessner Ute , Kopka Joachim , Boughton Berin A. 
Published: November 2022

AbstractPlant acclimation to low temperatures occurs through system-wide mechanisms that include proteome shifts, some of which occur at the level of protein synthesis. All proteins are synthesised by ribosomes. Rather than being monolithic, transcript-to-protein translation machines, ribosomes can be selective and cause effective proteome shifts required for successful temperature acclimation. Here, we use apical root meristems of germinating seedlings of the monocotyledonous plant barley as a model to study changes in protein abundance and synthesis rates during cold acclimation. We measure metabolic and physiological parameters that allow us to compare protein synthesis rates in different physiological states, e.g., in cold acclimation compared to the optimal temperature state. We show that ribosomal proteins are independently synthesised and assembled into ribosomal complexes in root proliferative tissue, and assess how the ribo-proteome shifts during cold may be associated with changes in synthesis and accumulation of macromolecular complexes. We demonstrate that translation initiation is the limiting step during cold acclimation and based on our data propose a model of a ribosomal code that depends on a reconfigured ribosome population, where as a mode of cold acclimation, specific ribosomal protein compositions may confer selective association capabilities between 60S subunits and 48S initiation complexes.