bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local Ancestry Inference for Complex Population Histories
Authors: Pearson Alice , Durbin Richard 
Published: March 2023

AbstractIt has become apparent from ancient DNA analysis, that the history of many human populations from across the globe are often complex, involving multiple population split, admixture, migration and isolation events. Local ancestry inference (LAI) aims to identify from which ancestral population chromosomal segments in admixed individuals are inherited. However, ancestry in existing LAI tools is characterised by a discrete population identity, a definition which is limited in the context of a complex demographic history involving multiple admixture events at different times. Moreover, many LAI tools rely on a reference panel of present day genomes that act as proxies for the ancestral populations. For ancient admixture events, these proxy genomes are likely only distantly related to the true ancestral populations. Here we present a new method that leverages advances in ancient DNA sequencing and genealogical inference to address these in issues in LAI. The method applies machine learning to tree sequences inferred for ancient and present day genomes and is based on a deterministic model of population structure, within which we introduce the concept of path ancestry. We show that the method is robust to a variety of demographic scenarios, generalises over model misspecification and that it outperforms a leading local ancestry inference tool. We further describe a downstream method to estimate the time since admixture for individuals with painted chromosomes. We apply the method to a large ancient DNA dataset covering Europe and West Eurasia and show that the inferred admixture ages are a better metric than sample ages alone for understanding movements of people across Europe in the past.
Long noncoding RNA-mediated epigenetic regulation of auxin-related genes controlling shade avoidance syndrome inArabidopsis thaliana
Authors: Mammarella María Florencia , Lucero Leandro , Hussain Nosheen , Muñoz-Lopez Aitor , Huang Ying , Ferrero Lucia , Fernandez-Milmanda Guadalupe L. , Manavella Pablo , Benhamed Moussa , Crespi Martin , Ballare Carlos L. , Marcos José Gutiérrez , Cubas Pilar , Ariel Federico 
Published: March 2023

ABSTRACTThe long noncoding RNA (lncRNA)AUXIN-REGULATED PROMOTER LOOP(APOLO) recognizes a subset of target loci across theArabidopsis thalianagenome by forming RNA-DNA hybrids (R-loop) and modulating local three-dimensional chromatin conformation. Here we show thatAPOLOis involved in regulating the shade avoidance syndrome (SAS) by dynamically modulating the expression of key factors. In response to far-red (FR) light, the expression ofAPOLOanticorrelates with its targetBRANCHED1(BRC1), a master regulator of shoot branching inArabidopsis thaliana.APOLOderegulation results inBRC1transcriptional repression and an increase in the number of branches.APOLOtranscriptional accumulation fine-tunes the formation of a repressive chromatin loop encompassing theBRC1promoter, which normally occurs only in leaves as well as in a late response to FR treatment in axillary buds. In addition, our data reveal thatAPOLOparticipates in leaf hyponasty, in agreement with its previously reported role in the control of auxin homeostasis through direct modulation ofYUCCA2(auxin synthesis),PIDandWAG2(auxin efflux). We found that direct application ofAPOLORNA to leaves results in a rapid increase in auxin accumulation that is associated with changes in the response of the plants to FR light. Collectively, our data support the view that lncRNAs coordinate the shade avoidance syndrome inArabidopsis thalianaand shed light on the potential of lncRNAs as bioactive exogenous molecules. Deploying exogenous RNAs that modulate plant-environment interactions are important new tools for sustainable agriculture.
Roles of microbiota in autoimmunity in Arabidopsis
Authors: Cheng Yu Ti , Thireault Caitlin A. , Paasch Bradley C. , Zhang Li , He Sheng Yang 
Published: March 2023

AbstractOver the past three decades, researchers have isolated plant mutants that display constitutively activated defense responses in the absence of pathogen infection. These mutants are called autoimmune mutants and are typically dwarf and/or bearing chlorotic/necrotic lesions. From a genetic screen forArabidopsisgenes involved in maintaining a normal leaf microbiota, we identifiedTIP GROWTH DEFECTIVE 1(TIP1), which encodes a S-acyltransferase, as a key player in guarding leaves against abnormal microbiota level and composition under high humidity conditions. Thetip1mutant has several characteristic phenotypes of classical autoimmune mutants, including a dwarf stature, displaying lesions, and having a high basal level of defense gene expression. Gnotobiotic experiments revealed that the autoimmune phenotypes of thetip1mutant are largely dependent on the presence of microbiota as axenictip1plants have markedly reduced autoimmune phenotypes. We found that the microbiota dependency of autoimmune phenotypes is shared by several “lesion mimic”-type autoimmune mutants inArabidopsis. Interestingly, autoimmune phenotypes caused by mutations inNLRgenes do not require the presence of microbiota and can even be partially alleviated by microbiota. Our results therefore suggest the existence of two classes of autoimmunity (microbiota-dependent vs. microbiota-independent) in plants. The observed interplay between autoimmunity and microbiota in the lesion mimic class of autoimmunity is reminiscent of the interactions between autoimmunity and dysbiosis in the animal kingdom.
An improvedNicotiana benthamianabioproduction chassis provides novel insights into nicotine biosynthesis
Authors: Vollheyde K , Dudley QM , Yang T , Oz MT , Mancinotti D , Olivera Fedi M , Heavens D , Linsmith G , Chhetry M , Smedley MA , Harwood WA , Swarbreck D , Geu-Flores F , Patron NJ 
Published: March 2023

AbstractThe model plantNicotiana benthamianais an increasingly attractive organism for the production of high-value, biologically active molecules. However,N. benthamianaaccumulates high levels of pyridine alkaloids, in particular nicotine, which complicates the downstream purification processes. Here, we report the assembly of an improvedN. benthamianagenome as well as the generation of low-nicotine lines by CRISPR/Cas9-based inactivation of berberine bridge enzyme-like proteins (BBLs). Triple as well as quintuple mutants accumulated 3-4 times less nicotine than the respective control lines. The availability of lines without functional BBLs allowed us to probe their catalytic role in nicotine biosynthesis, which has remained obscure. Notably, chiral analysis revealed that the enantiomeric purity of nicotine was fully lost in the quintuple mutants. In addition, precursor feeding experiments showed that these mutants cannot facilitate the specific loss of C6 hydrogen that characterizes natural nicotine biosynthesis. Our work delivers an improvedN. benthamianachassis for bioproduction and opens the possibility that BBLs are the sought-after coupling enzymes in nicotine biosynthesis.
Exploring the evolution and function of Canoe’s intrinsically disordered region in linking cell-cell junctions to the cytoskeleton during embryonic morphogenesis
Authors: Gurley Noah J. , Szymanski Rachel A , Dowen Robert H , Butcher T. Amber , Ishiyama Noboru , Peifer Mark 
Published: March 2023

AbstractOne central question for cell and developmental biologists is defining how epithelial cells can change shape and move during embryonic development without tearing tissues apart. This requires robust yet dynamic connections of cells to one another, via the cell-cell adherens junction, and of junctions to the actin and myosin cytoskeleton, which generates force. The last decade revealed that these connections involve a multivalent network of proteins, rather than a simple linear pathway. We focus onDrosophilaCanoe, homolog of mammalian Afadin, as a model for defining the underlying mechanisms. Canoe and Afadin are complex, multidomain proteins that share multiple domains with defined and undefined binding partners. Both also share a long carboxy-terminal intrinsically disordered region (IDR), whose function is less well defined. IDRs are found in many proteins assembled into large multiprotein complexes. We have combined bioinformatic analysis and the use of a series ofcanoemutants with early stop codons to explore the evolution and function of the IDR. Our bioinformatic analysis reveals that the IDRs of Canoe and Afadin differ dramatically in sequence and sequence properties. When we looked over shorter evolutionary time scales, we identified multiple conserved motifs. Some of these are predicted by AlphaFold to be alpha-helical, and two correspond to known protein interaction sites for alpha-catenin and F-actin. We next identified the lesions in a series of eighteencanoemutants, which have early stop codons across the entire protein coding sequence. Analysis of their phenotypes are consistent with the idea that the IDR, including its C-terminal conserved motifs, are important for protein function. These data provide the foundation for further analysis of IDR function.
The neurocellular implementation of representational geometry in primate prefrontal cortex
Authors: Lin Xiao-Xiong , Nieder Andreas , Jacob Simon N. 
Published: March 2023

SummaryModern neuroscience has seen the rise of a population-doctrine that represents cognitive variables using geometrical structures in activity space. Representational geometry does not, however, account for how individual neurons implement these representations. Here, leveraging the principle of sparse coding, we present a framework to dissect representational geometry into biologically interpretable components that retain links to single neurons. Applied to extracellular recordings from the primate prefrontal cortex in a working memory task with interference, the identified components revealed disentangled and sequential memory representations including the recovery of memory content after distraction, signals hidden to conventional analyses. Each component was contributed by small subpopulations of neurons with distinct electrophysiological properties and response dynamics. Modelling showed that such sparse implementations are supported by recurrently connected circuits as in prefrontal cortex. The perspective of neuronal implementation links representational geometries to their cellular constituents, providing mechanistic insights into how neural systems encode and process information.
Antibody-directed extracellular proximity biotinylation reveals Contactin-1 regulates axo-axonic innervation of axon initial segments
Authors: Ogawa Yuki , Lim Brian C. , George Shanu , Oses-Prieto Juan A. , Rasband Joshua M. , Eshed-Eisenbach Yael , Nair Supna , Boato Francesco , Peles Elior , Burlingame Alma L. , Aelst Linda Van , Rasband Matthew N. 
Published: March 2023

ABSTRACTAxon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we used antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we used CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We found Contactin-1 (Cntn1) among the previously unknown AIS proteins we identified. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS-extracellular matrix, and is required for AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.
Cell-Type Specific Connectivity of Whisker-Related Sensory and Motor Cortical Input to Dorsal Striatum
Authors: Sanabria Branden D. , Baskar Sindhuja S. , Yonk Alex J. , Lee Christian R. , Margolis David J. 
Published: March 2023

AbstractThe anterior dorsolateral striatum (DLS) is heavily innervated by convergent excitatory projections from the primary motor (M1) and sensory cortex (S1) and is considered an important site of sensorimotor integration. M1 and S1 corticostriatal synapses have functional differences in the strength of their connections with striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS, and as a result exert an opposing influence on sensory-guided behaviors. In the present study, we tested whether M1 and S1 inputs exhibit differences in the subcellular anatomical distribution onto striatal neurons. We injected adeno-associated viral vectors encoding spaghetti monster fluorescent proteins (sm.FPs) into M1 and S1, and used confocal microscopy to generate 3D reconstructions of corticostriatal inputs to single identified SPNs and FSIs obtained through ex-vivo patch-clamp electrophysiology. We found that SPNs are less innervated by S1 compared to M1, but FSIs receive a similar number of inputs from both M1 and S1. In addition, M1 and S1 inputs were distributed similarly across the proximal, medial, and distal regions of SPNs and FSIs. Notably, clusters of inputs were prevalent in SPNs but not FSIs. Our results suggest that SPNs have stronger functional connectivity to M1 compared to S1 due to a higher density of synaptic inputs. The clustering of M1 and S1 inputs onto SPNs but not FSIs suggest that cortical inputs are integrated through cell-type specific mechanisms and more generally have implications for how sensorimotor integration is performed in the striatum.Significance StatementThe dorsolateral striatum (DLS) is a key brain area involved in sensorimotor integration due to its dense innervation by the primary motor (M1) and sensory cortex (S1). However, the quantity and anatomical distribution of these inputs to the striatal cell population has not been well characterized. In this study we demonstrate that corticostriatal projections from M1 and S1 differentially innervate spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs) in the DLS. S1 inputs innervate SPNs less than M1 and are likely to form synaptic clusters in SPNs but not in FSIs. These findings suggest that sensorimotor integration is partly achieved by differences in the synaptic organization of corticostriatal inputs to local striatal microcircuits.
Studies in CRISPR-generated Mediterranean G6PD variant rats reveal G6PD orchestrates genome-wide DNA methylation and gene expression in vascular wall
Authors: Signoretti Christina , Gupte Sachin A. 
Published: March 2023

AbstractBackgroundRecent advances have revealed the importance of epigenetic modifications to gene regulation and transcriptional activity. DNA methylation, a determinant of genetic imprinting andde novosilencing of genes genome-wide, is known to be controlled by DNA methyltransferases (DNMT) and demethylases (TET) under disease conditions. However, the mechanism(s)/factor(s) influencing the expression and activity of DNMTs and TETs, and thus DNA methylation, in healthy vascular tissue is incompletely understood. Based on our recent studies, we hypothesized that glucose-6-phosphate dehydrogenase (G6PD) is a modifier of DNMT and TET expression and activity and an enabler of gene expression.MethodsIn aorta of CRISPR-edited rats with the Mediterranean G6PD variant we determined DNA methylation by whole-genome bisulfite sequencing, gene expression by RNA sequencing, and large artery stiffness by echocardiography.ResultsHere, we documented higher expression ofDnmt3a, Tet2, andTet3in aortas from Mediterranean G6PDS188Fvariant (a loss-of-function single nucleotide polymorphism) rats than their wild-type littermates. Concomitantly, we identified 17,618 differentially methylated loci genome-wide (5,787 hypermethylated loci, including down-regulated genes encoding inflammation- and vasoconstriction-causing proteins, and 11,827 hypomethylated loci, including up-regulated genes encoding smooth muscle cell differentiation- and fatty acid metabolism-promoting proteins) in aorta from G6PDS188Fas compared to wild-type rats. Further, we observed less large artery (aorta) stiffness in G6PDS188Fas compared to wild-type rats.ConclusionsThese results establish a noncanonical function of the wild-type G6PD and G6PDS188Fvariant in the regulation of DNA methylation and gene expression in healthy vascular tissue and reveals G6PDS188Fvariant contributes to reduce large artery stiffness.HighlightsThe wild-type G6PD and G6PDS188Fvariant regulates the expression and activity of nuclear DNMT and TET and selectively evokes hyper/hypo-methylation of loci/promoter regions genome-wide.G6PDS188Fvariant represses and activates genes detrimental and beneficial to vascular cell phenotype and function, respectively.G6PDS188Fvariant reduces large artery stiffness.
Model of multiperiod production-distribution for closed-loop supply chain considering carbon emission and traceability for agri-food products
Authors: Yuniarti Rahmi , Masudin Ilyas , Rusdiansyah Ahmad , Handayani Dwi Iryaning 
Published: March 2023

PurposeThis study aimed to develop the integration of the multiperiod production-distribution model in a closed-loop supply chain involving carbon emission and traceability. The developed model was for agricultural food (agri-food) products, considering the reverse flow of food waste from the disposal center (composting center) to producers.FindingsThe results indicate that integrating the production and distribution model considering food waste recycling provides low carbon emissions in lower total costs. The sensitivity analysis also found that there are trade-offs between production and distribution rate and food waste levels on carbon emission and traceability.Research limitations/implicationsThis study focuses on the mathematical modeling of a multiperiod production-distribution formulation for a closed-loop supply chain.Originality/valueThe model of the agri-food closed-loop supply chain in this study that considers food recycling and carbon emissions would help stakeholders involved in the agri-food supply chain to reduce food waste and carbon emissions.
The impact of corporate social responsibility decoupling on financial performance: the role of customer structure and operational slack
Authors: He Chang , Jia Fu , Wang Liukai , Chen Lujie , Fernandes Kieran 
Published: March 2023

PurposeCorporate social responsibility (CSR) decoupling indicates a misalignment between how firms report CSR and what firms actually practice with respect to CSR. The purpose of this paper is to examine the relationship between CSR decoupling and financial performance and the factors affecting this relationship.Design/methodology/approachThis paper collects and combines secondary panel data from multiple sources of Chinese listed firms from 2008 to 2020 to test the direct impact of CSR decoupling on firms’ financial performance and the moderating role of customer structure and operational slack.FindingsThis paper finds that CSR decoupling is negatively associated with firms’ financial performance. These findings further suggest that the negative relationship can be suppressed by customer stability and operational slack, but amplified by customer concentration. These conclusions remain robust to alternate measures of independent and dependent variables and narrower samples.Originality/valueIn the literature, the effect of CSR on firms’ financial performance is inconclusive. This is the first study to examine the impact of CSR decoupling on firms’ financial performance and the factors affecting this relationship. This paper contributes to the CSR decoupling literature from an operations and supply chain management perspective.
Effects of the anthropomorphic image of intelligent customer service avatars on consumers' willingness to interact after service failures
Authors: Yao Qi , Kuai Ling , Jiang Lan 
Published: March 2023

PurposeIntelligent customer service has started replacing human employees in providing services to customers in numerous industries. Based on the expectancy disconfirmation theory, this study explores how different types of anthropomorphic avatar images of the intelligent customer service would affect consumer responses such as the willingness to interact, in the context of a service failure. The underlying mechanism and boundary conditions are also examined.Design/methodology/approachTwo experimental studies were conducted to investigate the effect of the anthropomorphic image of intelligent customer service on consumers' willingness to interact and the potential role of consumer expectation and disappointment, following a service failure (Study 1). The moderating effect of anthropomorphic type was also explored (Study 2).FindingsIn the context of a customer service failure, an anthropomorphized intelligent customer service avatar that appeared competent (vs. warm) induced higher customer disappointment. However, if the anthropomorphic avatar had a cartoon-like appearance, the effect of avatar image perception (competent vs. warm) on consumers' willingness to interact diminishes.Originality/valueThis research enriches and expands the literature on interactive marketing and artificial intelligence and provides practical guidance for companies to design or choose avatar images for intelligent customer service.
Oxidation and oxidative stability in emulsions
Authors: Ghelichi Sakhi , Hajfathalian Mona , Yesiltas Betül , Sørensen Ann‐Dorit Moltke , García‐Moreno Pedro J. , Jacobsen Charlotte 
Published: March 2023

AbstractEmulsions are implemented in the fabrication of a wide array of foods and therefore are of great importance in food science. However, the application of emulsions in food production is restricted by two main obstacles, that is, physical and oxidative stability. The former has been comprehensively reviewed somewhere else, but our literature review indicated that there is a prominent ground for reviewing the latter across all kinds of emulsions. Therefore, the present study was formulated in order to review oxidation and oxidative stability in emulsions. In doing so, different measures to render oxidative stability to emulsions are reviewed after introducing lipid oxidation reactions and methods to measure lipid oxidation. These strategies are scrutinized in four main categories, namely storage conditions, emulsifiers, optimization of production methods, and antioxidants. Afterward, oxidation in all types of emulsions, including conventional ones (oil‐in‐water and water‐in‐oil) and uncommon emulsions in food production (oil‐in‐oil), is reviewed. Furthermore, the oxidation and oxidative stability of multiple emulsions, nanoemulsions, and Pickering emulsions are taken into account. Finally, oxidative processes across different parent and food emulsions were explained taking a comparative approach.