bluuebunny/crossref_metadata_2025_split huggingface dataset:
SifiNet: A robust and accurate method to identify feature gene sets and annotate cells
Authors: Gao Qi , Ji Zhicheng , Wang Liuyang , Owzar Kouros , Li Qi-Jing , Chan Cliburn , Xie Jichun 
Published: May 2023

AbstractSifiNet is a robust and accurate computational pipeline for identifying distinct gene sets, extracting and annotating cellular subpopulations, and elucidating intrinsic relationships among these subpopulations. Uniquely, SifiNet bypasses the cell clustering stage, commonly integrated into other cellular annotation pipelines, thereby circumventing potential inaccuracies in clustering that may compromise subsequent analyses. Consequently, SifiNet has demonstrated superior performance in multiple experimental datasets compared with other state-of-the-art methods. SifiNet can analyze both single-cell RNA and ATAC sequencing data, thereby rendering comprehensive multiomic cellular profiles. It is conveniently available as an open-source R package.
A combination of convergent extension and differential adhesion explains the shapes of elongating gastruloids
Authors: de Jong Martijn A. , Adegeest Esmée , Bérenger-Currias Noémie M. L. P. , Mircea Maria , Merks Roeland M. H. , Semrau Stefan 
Published: May 2023

AbstractGastruloids have emerged as highly usefulin vitromodels of mammalian gastrulation. One of the most striking features of 3D gastruloids is their elongation, which mimics the extension of the embryonic anterior-posterior axis. Although axis extension is crucial for development, the underlying mechanism has not been fully elucidated in mammalian species. Gastruloids provide an opportunity to study this morphogenic processin vitro. Here, we measure and quantify the shapes of elongating gastruloids and show, by Cellular Potts model simulations, that a combination of convergent extension and differential adhesion can explain the observed shapes. We reveal that differential adhesion alone is insufficient and also directly observe hallmarks of convergent extension by time-lapse imaging of gastruloids. Finally, we show that gastruloid elongation can be abrogated by inhibition of the Rho kinase pathway, which is involved in convergent extensionin vivo. All in all, our study demonstrates, how gastruloids can be used to elucidate morphogenic processes in embryonic development.
FuzzyPPI: Human Proteome at Fuzzy Semantic Space
Authors: Halder Anup Kumar , Bandyopadhyay Soumyendu Sekhar , Jedrzejewski Witold , Basu Subhadip , Sroka Jacek 
Published: May 2023

AbstractLarge scale protein-protein interaction (PPI) network of an organism provides key insights into its cellular and molecular functionalities, signaling pathways and underlying disease mechanisms. For any organism the total number of unexplored protein interactions significantly outnumbers all known positive and negative interactions. For Human, all known PPI datasets, contain only ∼ 5.61 million positive and ∼ 0.76 million negative interactions, that together is ∼ 3.1% of potential interactions. Moreover, conventional PPI prediction methods produce binary results. At the same time, recent studies show that protein binding affinities may prove to be effective in detecting protein complexes, disease association analysis, signaling network reconstruction, etc. Keeping these in mind, we present a fuzzy semantic scoring function using the Gene Ontology (GO) graphs to assess the binding affinity between any two proteins at an organism level. We have implemented a distributed algorithm in Apache Spark that computes this function and used it to process a Human PPI network of ∼ 180 million potential interactions resulting from 18 994 reviewed proteins for which GO annotations are available. The quality of the computed scores has been validated with respect to the availablestate-of-the-artmethods on benchmark data sets. The resulting scores are published with a web-server for non-commercial use at:http://fuzzyppi.mimuw.edu.pl/.
Pre-gelation staining expansion microscopy (PS-ExM) for visualization of thePlasmodiumliver stage
Authors: Atchou Kodzo , Berger Bianca Manuela , Heussler Volker , Ochsenreiter Torsten 
Published: May 2023

AbstractFluorescence and light microscopy are important tools in the history of natural science. However, the resolution of microscopes is limited by the diffraction of light. One possible method to circumvent this physical restriction is the recently developed expansion microscopy (ExM). By physically expanding the sample in a swellable hydrogel, biomolecules are separated in space allowing to image molecules that are otherwise difficult to study due to their size or complexity. Furthermore, the improved resolution is useful to study protein localization and interactions. However, the original ultrastructure ExM (U-ExM) protocol is very time-consuming, and some epitopes are lost during the process. In this study, we developed a shortened pre-gelation staining ExM (PS-ExM) protocol and tested it to investigate thePlasmodiumliver stage. The protocol presented in this study allows expanding pre-stained samples, which results in shorter incubation times, better preservation of some epitopes, and the advantage that non-expanded controls can be performed alongside using the same staining protocol. The protocol applicability was accessed throughout thePlasmodiumliver stage showing isotropic five-fold expansion. Furthermore, we used PS-ExM to visualize the association of lysosomes to the parasitophorous vacuole membrane (PVM) as an example of visualizing host-pathogen interaction. We are convinced that this new tool will be helpful for a deeper understanding of the biology of thePlasmodiumliver stage.
Liver Receptor Homolog-1 (LRH-1/NR5A2) orchestrates hepatic inflammation and TNF-induced cell death
Authors: Lambrecht Rebekka , Eugenia Delgado M. , Gloe Vincent , Schuetz Karina , Plazzo Anna Pia , Franke Barbara , Phan Truong San , Fleming Jennifer , Mayans Olga , Brunner Thomas 
Published: May 2023

SummaryLiver Receptor Homolog-1 (LRH-1/NR5A2) is a nuclear receptor that has been shown to promote apoptosis resistance in various tissues and disease contexts, however, its role in liver cell death remains unexplored. Deletion of LRH-1 in hepatocytes developed into a mild steatosis and inflammation already under steady-state conditions. Unexpectedly, hepatocyte-specific deletion of LRH-1 also resulted in a profound protection of mice from TNF-induced hepatocyte apoptosis and associated hepatitis. LRH-1-deficient hepatocytes showed elevated NF-ⲕB activity, while LRH-1 overexpression inhibited NF-ⲕB activity. This inhibition was based on direct physical interaction of the ligand-binding domain of LRH-1 and the Rel homology domain of NF-ⲕB subunit RelA. Mechanistically, we found that increased transcription of anti-apoptotic NF-ⲕB target genes, together with proteasomal degradation of pro-apoptotic BIM via regeneration-driven EGF receptor signaling, prevented mitochondrial apoptosis, ultimately protecting mice from TNF-induced liver damage. Collectively, our study demonstrates that LRH-1 is a critical modulator of cell death and inflammation in the healthy and diseased liver.HighlightsHepatic LRH-1 deletion causes mild liver steatosis, fibrosis, and inflammation.Female LRH-1-deficient mice are protected from TNF-induced liver damage.LRH-1 interacts with NF-ⲕB and inhibits its activity.LRH-1 deletion-provoked inflammation causes degradation of pro-apoptotic protein BIM.Graphical abstract
Investigating the ATP binding pocket of CX3CL1 binding protein 2 usingin silicoapproach
Authors: Kumari Rimjhim , Kaur Satinder , Hora Rachna , Mishra Prakash Chandra 
Published: May 2023

AbstractPlasmodium falciparum(Pf) causes the most fatal form of malaria owing to its ability to cytoadhere in the microvasculature of various organs in the body. In addition to the Pf erythrocyte membrane protein 1 (PfEMP1) family that binds diverse host receptors, CX3CL1 binding proteins 1 and 2 (CBP1 and 2) also bind the endothelial chemokine ‘CX3CL1’ to effect cytoadhesion of parasite infected erthrocytes. CBP2 is a multifaceted protein that binds nucleic acids, Pf skeleton binding protein (PfSBP1) and ATP. ATP binding to the cytoplasmic domain of CBP2 (cCBP2) induces structural changes in the protein, and hints at its role in cell signaling. In this study, we have attempted to identify the ATP binding pocket of CBP2 using anin silicoapproach. We have also delineated the type of interactions and amino acid residues that are likely to bind ATP. As CX3CL1 binding proteins are central to parasite biology, the obtained information is likely to form the basis for inhibitor and drug design against this molecule.
Comparison of histological delineations of medial temporal lobe cortices by four independent neuroanatomy laboratories
Authors: Wuestefeld Anika , Baumeister Hannah , Adams Jenna N. , de Flores Robin , Hodgetts Carl , Mazloum-Farzaghi Negar , Olsen Rosanna K. , Puliyadi Vyash , Tran Tammy T. , Bakker Arnold , Canada Kelsey L. , Dalton Marshall A. , Daugherty Ana M. , Joie Renaud La , Wang Lei , Bedard Madigan , Buendia Esther , Chung Eunice , Denning Amanda , del Mar Arroyo-Jiménez María , Artacho-Pérula Emilio , Irwin David J. , Ittyerah Ranjit , Lee Edward B. , Lim Sydney , del Pilar Marcos-Rabal María , de Onzoño Martin Maria Mercedes Iñiguez , Lopez Monica Munoz , de la Rosa Prieto Carlos , Schuck Theresa , Trotman Winifred , Vela Alicia , Yushkevich Paul , Amunts Katrin , Augustinack Jean C. , Ding Song-Lin , Insausti Ricardo , Kedo Olga , Berron David , Wisse Laura E.M. 
Published: May 2023

AbstractThe medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer’s disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the cortices that make up the parahippocampal gyrus (entorhinal and parahippocampal cortices) and the adjacent Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations.Nissl-stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 µm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized (20X resolution) slices with 5 mm spacing. Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail.Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists’ agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed more gradually.The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically-informed human neuroimaging research on the MTL cortex.
ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism sensing paracellular diffusion barrier alteration inDrosophilaepithelial cells
Authors: de Bournonville Thomas Esmangart , Jaglarz Mariusz K. , Durel Emeline , Le Borgne Roland 
Published: May 2023

SummaryBarrier functions of proliferative epithelia are constantly challenged by mechanical and chemical constraints. How epithelia respond to and cope with disturbances of the paracellular diffusion barrier to allow tissue integrity maintenance has been poorly characterized. Cellular junctions play an important role in this process and intracellular traffic contribute to their homeostasis. Here, we reveal that, inDrosophilapupal notum, alteration of the bi- or tricellular septate junctions (SJs) triggers a mechanism with two prominent outcomes. On one hand, there is an increase in the levels of E-cadherin, F- Actin and non-muscle myosin II in the plane of adherens junctions. On the other hand, β-integrin/Vinculin-positive cell contacts are reinforced along the lateral and basal membranes. We report that the weakening of SJ integrity, caused by the depletion of bi- or tricellular SJ components, reduces ESCRT-III/Vps32/Shrub-dependent degradation and promotes instead Retromer-dependent recycling of SJ components. The consequence of the reduction in Shrub-dependent degradation extends to other transmembrane protein cargoes. Consequently, this trigger increased levels of β- integrin, Crumbs and the Crumbs effectors β-Heavy Spectrin Karst. We propose a mechanism by which epithelial cells, upon sensing alterations in the paracellular diffusion barrier, target Shrub to adjust the degradation/recycling balance and thereby compensate for barrier defects while maintaining epithelial integrity.
Epigallocatechin Gallate Modulates Microglia Phenotype to Suppress Pro-Inflammatory Signalling Cues and Inhibit Phagocytosis
Authors: Regan Philip , Hole Katriona L , Sero Julia , Williams Robert J 
Published: May 2023

AbstractMicroglia are crucial players in the pathogenesis of late onset Alzheimer’s Disease (AD), with evidence for both deleterious and beneficial effects. Identifying interventions to modulate microglial responsiveness, to promote Amyloid β (Aβ) clearance, disrupt plaque formation or to dampen excessive inflammation has therapeutic potential. Bioavailable flavonoids such as the flavan 3-ols are of interest due to their antioxidant, metal chelating, signalling and anti-inflammatory potential. Primary microglia were treated with a series of structurally related flavanol 3-ols to assess effects on phagocytosis, cytokine release and transcriptional responses by RNA sequencing. Data indicated that the extent of hydroxylation and the presence of the galloyl moiety were strong determinants of flavan 3-ol activity. Epigallocatechin gallate (EGCG) was the most effective flavan-3-ol tested and strongly inhibited phagocytosis of Aβ independent of any metal chelating properties suggesting a more direct modulation of microglia responsiveness. EGCG was broadly anti-inflammatory, reducing cytokine release and downregulating transcription particularly of components of the microglia extracellular matrix such as MMP3 and SerpinB2. Collectively this brings new insight into the actions of flavonoids on microglial responsiveness with potential implications for the therapeutic use of EGCG and structurally related flavanol-3-ols in AD.
Evolutionary conservation of embryonic DNA methylome remodelling in distantly related teleost species
Authors: Ross Samuel E. , Vázquez-Marín Javier , Gert Krista R.B. , González-Rajal Álvaro , Dinger Marcel E. , Pauli Andrea , Martínez-Morales Juan Ramon , Bogdanovic Ozren 
Published: May 2023

ABSTRACTMethylation of cytosines in the CG context (mCG) is the most abundant DNA modification in vertebrates that plays crucial roles in cellular differentiation and identity. After fertilization, DNA methylation patterns inherited from parental gametes are remodelled into a state compatible with embryogenesis. In mammals, this is achieved through the global erasure and re-establishment of DNA methylation patterns. However, in non-mammalian vertebrates like zebrafish, no global erasure has been observed. To investigate the evolutionary conservation and divergence of DNA methylation remodelling in teleosts, we generated base resolution DNA methylome datasets of developing medaka and medaka-zebrafish hybrid embryos. In contrast to previous reports, we show that medaka display comparable DNA methylome dynamics to zebrafish with high gametic mCG levels (sperm: ∼90%; egg: ∼75%), and adoption of a paternal-like methylome during early embryogenesis, with no signs of prior DNA methylation erasure. We also demonstrate that non-canonical DNA methylation (mCH) reprogramming at TGCT tandem repeats is a conserved feature of teleost embryogenesis. Lastly, we find remarkable evolutionary conservation of DNA methylation remodelling patterns in medaka-zebrafish hybrids, indicative of compatible DNA methylation maintenance machinery in far-related teleost species. Overall, these results suggest strong evolutionary conservation of DNA methylation remodelling pathways in teleosts, which is distinct from the global DNA methylome erasure and reestablishment observed in mammals.
Cinnamic acid and p-coumaric acid are metabolized to 4-hydroxybenzoic acid byYarrowia lipolytica
Authors: Konzock Oliver , Mohedano Marta Tous , Cibin Irene , Chen Yun , Norbeck Joakim 
Published: May 2023

AbstractThe transition towards a bioeconomy requires the microbial production of various products from renewable resources such as lignocellulosic hydrolysate.Yarrowia lipolyticahas been explored as a potential production host for flavonoid synthesis due to its high tolerance to aromatic acids and ability to supply malonyl-CoA. However, little is known about its ability to consume the precursors cinnamic andp-coumaric acid. In this study, we demonstrate thatY. lipolyticacan consume these precursors through multiple pathways that are partially dependent on the cultivation medium. We constructed a collection of 15 P450 protein knock-out strains to identify the genes responsible for the reaction and identified YALI1_B28430g as the gene encoding for a protein with a trans-cinnamate 4-monooxygenase activity that converts cinnamic acid top-coumaric acid and named it TCM1.p-Coumaric acid in turn is further converted to 4-hydroxybenzoic acid. Our findings provide new insight into the metabolic capabilities ofY. lipolyticaand will be essential for the future construction of better flavonoid production strains.
Applying genomic approaches to identify historic population declines in European forest bats
Authors: Razgour Orly , Montauban Cecilia , Festa Francesca , Whitby Daniel , Juste Javier , Ibáñez Carlos , Rebelo Hugo , Afonso Sandra , Bekaert Michael , Jones Gareth , Williams Carol , Boughey Katherine 
Published: May 2023

AbstractAnthropogenically-driven environmental changes over the past two centuries have led to severe biodiversity loss, most prominently in the form of loss of populations and individuals. Better tools are needed to assess the magnitude of these wildlife population declines. Anecdotal evidence suggests European bat populations have suffered substantial declines in the past few centuries. However, there is little empirical evidence of these declines that can be used to put more recent population changes into historic context and set appropriate targets for species recovery.This study is a collaboration between academics and conservation practitioners to develop molecular approaches capable of providing quantitative evidence of historic population changes and their drivers that can inform the assessment of conservation status and conservation management. We generated a genomic dataset for the Western barbastelle,Barbastella barbastellus,a globally Near Threatened and regionally Vulnerable bat species, including colonies from across the species’ British and Iberian ranges. We used a combination of landscape genetics and approximate Bayesian computation model-based inference of demographic history to identify both evidence of population size changes and possible drivers of these changes.We found that levels of genetic diversity increased and inbreeding decreased with increasing broadleaf woodland cover around the colony location. Genetic connectivity was impeded by artificial lights and facilitated by the combination of rivers and broadleaf woodland cover.The demographic history analysis showed that both the northern and southern British barbastelle populations have declined by 99% over the past 330-548 years. These declines may have been triggered by loss of large oak trees and native woodlands due to shipbuilding during the early colonial period.Synthesis and applications.Genomic approaches can be applied to provide a better understanding of the conservation status of threatened species, within historic and contemporary context, and inform their conservation management. This study shows how we can bridge the implementation gap and promote the application of genomics in conservation management through co-designing studies with conservation practitioners and co-developing applied management targets and recommendations.
Orai mediated Calcium entry determines activity of central dopaminergic neurons by regulation of gene expression
Authors: Mitra Rishav , Richhariya Shlesha , Hasan Gaiti 
Published: May 2023

AbstractMaturation and fine-tuning of neural circuits frequently requires neuromodulatory signals that set the excitability threshold, neuronal connectivity and synaptic strength. Here we present a mechanistic study of how neuromodulator stimulated intracellular Ca2+signals, through the store - operated Ca2+channel Orai, regulate intrinsic neuronal properties by control of developmental gene expression in flight promoting central dopaminergic neurons (fpDANs). The fpDANs receive cholinergic inputs for release of dopamine at a central brain tripartite synapse that sustains flight (Sharma and Hasan, 2020). Cholinergic inputs act on the muscarinic acetylcholine receptor to stimulate intracellular Ca2+release through the endoplasmic reticulum (ER) localised inositol 1,4,5-trisphosphate receptor followed by ER-store depletion and Orai mediated store-operated Ca2+entry (SOCE). Analysis of gene expression in fpDANs followed by genetic, cellular and molecular studies identified Orai-mediated Ca2+entry as a key regulator of excitability in fpDANs during circuit maturation. SOCE activates the transcription factor Trithorax-like (Trl) which in turn drives expression of a set of genes includingSet2, that encodes a histone 3 Lysine 36 methyltransferase (H3K36me3). Set2 function establishes a positive feedback loop, essential for receiving neuromodulatory cholinergic inputs and sustaining SOCE. Chromatin modifying activity of Set2 changes the epigenetic status of fpDANs and drives expression of key ion channel and signaling genes that determine fpDAN activity. Loss of activity reduces the axonal arborisation of fpDANS within the MB lobe, and prevents dopamine release required for maintenance of long flight.HighlightsStore-operated Ca2+entry (SOCE) through Orai is required in a set of flight-promoting central dopaminergic neurons (fpDANs) during late pupae and early adults to establish their gene expression profile.SOCE activates a homeobox transcription factor, ‘Trithorax-like’ and thus regulates expression of histone modifiers Set2 andE(z)to generate a balance between opposing epigenetic signatures of H3K36me3 and H3K27me3 on downstream genes.SOCE drives a transcriptional feedback loop to ensure expression of key genes required for neuronal function including the muscarinic acetylcholine receptor (mAChR) and the inositol 1,4,5-trisphosphate receptor (itpr).The transcriptional program downstream of SOCE is key to functional maturation of the dopaminergic neurons, enabling their neuronal excitability, axonal arborization and synaptic transmission required for adult flight.