bluuebunny/crossref_metadata_2025 huggingface dataset:
A nucleosome switch primes Hepatitis B Virus infection
Authors: Prescott Nicholas A. , Mansisidor Andrés , Bram Yaron , Biaco Tracy , Rendleman Justin , Faulkner Sarah C. , Lemmon Abigail A. , Lim Christine , Hamard Pierre-Jacques , Koche Richard P. , Risca Viviana I. , Schwartz Robert E. , David Yael
Published: March 2023

Chronic hepatitis B virus (HBV) infection is an incurable global health threat responsible for causing liver disease and hepatocellular carcinoma. During the genesis of infection, HBV establishes an independent minichromosome consisting of the viral covalently closed circular DNA (cccDNA) genome and host histones. The viral X gene must be expressed immediately upon infection to induce degradation of the host silencing factor, Smc5/6. However, the relationship between cccDNA chromatinization and X gene transcription remains poorly understood. Establishing a reconstituted viral minichromosome platform, we found that nucleosome occupancy in cccDNA drives X transcription. We corroborated these findings in cells and further showed that the chromatin destabilizing molecule CBL137 inhibits X transcription and HBV infection in hepatocytes. Our results shed light on a long-standing paradox and represent a potential new therapeutic avenue for the treatment of chronic HBV infection.
A proximity-dependent biotinylation map of cytosol-facing organelle outer membrane proteome in living Arabidopsis cells
Authors: Bao Xinyue , Jia Huifang , Zhang Xiaoyan , Zhao Yanming , Li Xiangyun , Lin Ping , Ma Chongyang , Wang Pengcheng , Song Chun-Peng , Zhu Xiaohong
Published: March 2023

The cytosol-facing outer membrane (OM) of organelles communicates with other cellular compartments to exchange proteins, metabolites and signaling molecules. Cellular surveillance systems also target OM-resident proteins to control organellar homeostasis and ensure cell survival under stress. Using traditional approaches to discover OM proteins and identify their dynamically interacting partners remains challenging. In this study, we developed an OM proximity labeling (OMPL) system using biotin ligase-mediated proximity biotinylation to map the proximity proteome of the OMs of mitochondria, chloroplasts, and peroxisomes in living Arabidopsis (Arabidopsis thaliana) cells. We demonstrate the power of this system with the discovery of cytosolic factors and OM receptor candidates involved in local protein translation and translocation, membrane contact sites, and organelle quality control. This system also performed admirably for the rapid isolation of intact mitochondria and peroxisomes. Our data support the notion that TOM20-3 is a candidate for both a mitochondrial and a chloroplast receptor, and that PEX11D is a candidate for a peroxisome receptor for the coupling of protein translation and import. OMPL-generated OM proximity proteomes are valuable sources of candidates for functional validation and suggest directions for further investigation of important questions in cell biology.
Long-read sequence analysis of MMEJ-mediated CRISPR genome editing reveals complex on-target vector insertions that may escape standard PCR-based quality control
Authors: Higashitani Yuki , Horie Kyoji
Published: March 2023

CRISPR genome editing is a powerful tool for elucidating biological functions. To modify the genome as intended, it is essential to understand the various modes of recombination that can occur. In this study, we report unexpected complex vector insertions that were identified during the generation of conditional alleles by CRISPR editing using microhomology-mediated end joining (MMEJ). The targeting vector contained two loxP sequences and flanking 40-bp microhomologies. The genomic regions corresponding to the loxP sequences were cleaved with Cas9 in mouse embryonic stem cells. PCR screening for targeted recombination revealed a high frequency of bands of a larger size than expected. Nanopore sequencing of these bands revealed complex vector insertions mediated not only by MMEJ but also by non-homologous end joining and homologous recombination in at least 17% of the clones. A new band appeared upon improving the PCR conditions, suggesting the presence of unexpectedly modified alleles that escape standard PCR screening. This prompted us to characterize the recombination of each allele of the genome-edited clones using heterozygous single nucleotide polymorphisms, leading to confirmation of the presence of homozygous alleles. Our study indicates that careful quality control of genome-edited clones is needed to exclude complex, unexpected, on-target vector insertion.
PPP1R3B is a metabolic switch that shifts hepatic energy storage from lipid to glycogen
Authors: Creasy Kate Townsend , Mehta Minal B. , Park Joseph , Schneider Carolin V. , Shewale Swapnil V. , Millar John S. , Hand Nicholas J. , Baur Joseph A. , Rader Daniel J.
Published: March 2023

Obesity is a growing worldwide epidemic that carries numerous metabolic complications including increased risk of type 2 diabetes (T2D), cardiovascular disease (CVD), and non-alcoholic fatty liver disease (NAFLD). Multiple genome-wide association studies (GWAS) have associated thePPP1R3Blocus with cardiometabolic traits including fasting glucose and insulin levels (T2D traits), plasma lipids (CVD traits), and indications of hepatic steatosis and liver damage (NAFLD traits)1–5. ThePPP1R3Bgene encodes the glycogen regulatory protein PPP1R3B (also known as GL) which has an established role in liver glycogen metabolism and plasma glucose homeostasis6,7. The metabolic and NAFLD GWAS single nucleotide polymorphisms (SNPs) in this region, which are all in high linkage disequilibrium, result in increased liverPPP1R3Bexpression and hepatic glycogen accumulation, but have provided conflicting results on the impacts on hepatic steatosis and liver damage. Here we investigate the consequences of bothPpp1r3boverexpression and deletion in mouse and cell models and find that dysregulatedPpp1r3bexpression in either direction promotes metabolic dysfunction and liver injury. Hepatocyte overexpression ofPpp1r3bincreases hepatic glycogen storage, prolongs fasting blood glucose levels, and confers protection from hepatic steatosis, but increases plasma ALT in aged animals. Conversely, deletion of hepatocytePpp1r3beliminates hepatic glycogen, causes impaired glucose disposal, and results in hepatic steatosis with age or high sucrose diet. We investigated the metabolic pathways contributing to steatosis and found thatPpp1r3bdeletion and diminished glycogenesis diverts the storage of exogenous glucose to hepatic triglycerides (TG), and stored liver lipids are preferentially used for energy during fasting through lipid oxidation and ketogenesis. Further, we interrogated two large human biobank cohorts and found carriers of SNPs associated with increasedPPP1R3Bexpression have increased plasma glucose, decreased hepatic fat, and lower plasma lipids, while putative loss-of-function (pLoF) variant carriers have increased hepatic fat and elevated plasma ketones and lipids, consistent with the results seen in our mouse models. These findings suggest hepatic PPP1R3B serves as a metabolic switch favoring hepatic energy storage as glycogen instead of TG.
Mutant huntingtin expression in the hypothalamus promotes ventral striatal neuropathology
Authors: Soylu-Kucharz Rana , Adlesic Natalie , Davidsson Marcus , Björklund Tomas , Björkqvist Maria , Petersén Åsa
Published: March 2023

Huntington’s disease is a fatal neurodegenerative disorder caused by an expanded CAG triplet repeat in the huntingtin (HTT) gene. Previous research focused on neuropathology in the striatum and its association with a typical movement disorder. Direct effects of mutant HTT (mHTT) in the striatum may cause neuropathology, although non-cell autonomous effects have also been suggested. Important non-motor features of HD include psychiatric symptoms and metabolic dysfunction, which may be linked to hypothalamic neuropathology. As hypothalamic neurons project to the ventral striatum, we hypothesized that expression of mHTT in the hypothalamus leads to disrupted neurotransmission in the ventral striatum and causes pathology. The overall aim of this study was to investigate the impact of mHTT expression in the hypothalamus on ventral striatal neuropathology and its contribution to non-HD motor symptoms. We demonstrate that selective expression of mHTT in the hypothalamus leads to the loss of dopamine and cAMP-regulated phosphoprotein (DARPP-32) immunopositive neurons in the ventral striatum in mice. Contrary to the effects of direct expression of mHTT in the hypothalamus, selective overexpression of mHTT in the ventral striatum does not affect body weight. Selective expression of mHTT in the ventral striatum leads to mHTT inclusion formation and loss of DARPP-32 neurons without affecting motor activity or anxiety-like behavior. We show that DARPP-32 neuron loss in the ventral striatum is recapitulated in the R6/2 mouse model of HD. Chemogenetic activation of hypothalamic neurons projecting to the ventral striatum had a blunted response in the R6/2 mice compared to wild-type mice, indicating a disrupted hypothalamus-ventral striatal circuitry. In summary, the expression of mHTT in the hypothalamus may impact the development of ventral striatal pathology in mice. This opens the possibility that non-cell-autonomous effects in the reward circuitry play a role in HD.
The Golgi checkpoint: Golgi unlinking during G2 is required for correct spindle formation and cytokinesis
Authors: Mascanzoni Fabiola , Ayala Inmaculada , Iannitti Roberta , Luini Alberto , Colanzi Antonino
Published: March 2023

The decision to enter mitosis requires not only the control of DNA replication but also additional and crucial preparatory steps such as, for example, partial disassembly of the Golgi complex during G2. The Golgi complex is fundamental for the processing and sorting of proteins and lipids in the secretory pathway. It is organized as stacks of cisternae laterally connected by tubules to form a continuous Golgi ribbon. During G2, the Golgi ribbon is unlinked into isolated stacks in preparation for cell division. This structural reorganization is necessary for entry into mitosis, indicating that a “Golgi mitotic checkpoint” controls the correct segregation of this organelle. To understand the physiological significance of the pre-mitotic Golgi unlinking, we devised a strategy to accumulate cells in G2 with an intact Golgi ribbon and then induce entry into mitosis. Here, we show that forcing the entry of cells into mitosis with an intact Golgi ribbon causes remarkable cell division defects, including spindle multipolarity and binucleation, favoring cell transformation. We also find that the cells entering mitosis with an intact Golgi ribbon show reduced levels at the centrosome of the kinase Aurora-A, a pivotal regulator of spindle formation. Overexpression of Aurora-A rescues spindle formation, indicating that the Golgi-dependent Aurora-A recruitment has a crucial role in spindle formation. Thus, our results show that alterations of the pre-mitotic Golgi segregation have profound consequences on the fidelity of the mitotic process, representing potential risk factors for cell transformation and cancer development.
Identification and characterization of structural and regulatory cell-shape determinants inHaloferax volcanii
Authors: Schiller Heather , Kouassi Joshua , Hong Yirui , Rados Theopi , Kwak Jasmin , DiLucido Anthony , Safer Daniel , Marchfelder Anita , Pfeiffer Friedhelm , Bisson-Filho Alexandre , Schulze Stefan , Pohlschroder Mechthild
Published: March 2023

Archaea play indispensable roles in global biogeochemical cycles, yet many critical cellular processes, including cell-shape determination, are poorly understood.Haloferax volcanii, a model haloarchaeon, forms rods and disks, depending on growth conditions. Here, we used a combination of iterative proteomics, genetics, and live-cell imaging to identify distinct mutants that only form rods or disks. We compared the proteomes of the mutants with wild-type cells across growth phases, thereby distinguishing between protein abundance changes specific to cell shape and those related to growth phases. The corresponding results indicated a diverse set of proteins, including transporters, transducers, signaling components, and transcriptional regulators, as important for cell-shape determination. We also identified structural proteins, including a previously unknown cytoskeletal element, theHfx. volcaniiactin homolog volactin, which plays a role in disk-shape morphogenesis. In summary, we gleaned important insights into archaeal cell-shape determination, with possible implications for understanding the evolution of cell morphology regulation across domains.
Prediction of SARS-CoV-2 transmission dynamics based on population-level cycle threshold values: A Machine Learning and mechanistic modeling study
Authors: Khan Afraz A. , Sbihi Hind , Irvine Michael A. , Jassem Agatha N. , Joffres Yayuk , Klaver Braeden , Janjua Naveed , Bharmal Aamir , Ng Carmen H. , Wilmer Amanda , Galbraith John , Romney Marc G. , Henry Bonnie , Hoang Linda M. N. , Krajden Mel , Hogan Catherine A.
Published: March 2023

Background

Polymerase chain reaction (PCR) cycle threshold (Ct) values can be used to estimate the viral burden of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) and predict population-level epidemic trends. We investigated the use of machine learning (ML) and epidemic transmission modeling based on Ct value distribution for SARS-CoV-2 incidence prediction during an Omicron-predominant period.

Methods

Using simulated data, we developed a ML model to predict the reproductive number based on Ct value distribution, and validated it on out-of-sample province-level data. We also developed an epidemiological model and fitted it to province-level data to accurately predict incidence.

Results

Based on simulated data, the ML model predicted the reproductive number with highest performance on out-of-sample province-level data. The epidemiological model was validated on outbreak data, and fitted to province-level data, and accurately predicted incidence.

Conclusions

These modeling approaches can complement traditional surveillance, especially when diagnostic testing practices change over time. The models can be tailored to different epidemiological settings and used in real time to guide public health interventions.

Funding

This work was supported by funding from Genome BC, Michael Smith Foundation for Health Research and British Columbia Centre for Disease Control Foundation to C.A.H. This work was also funded by the Public Health Agency of Canada COVID-19 Immunity Task Force COVID-19 Hot Spots Competition Grant (2021-HQ-000120) to M.G.R.
The commensal protistTritrichomonas musculusexhibits a dynamic life cycle that induces extensive remodeling of the gut microbiota
Authors: Popovic Ana , Cao Eric Yixiao , Han Joanna , Nursimulu Nirvana , Alves-Ferreira Eliza V.C. , Burrows Kyle , Kennard Andrea , Alsmadi Noor , Grigg Michael E. , Mortha Arthur , Parkinson John
Published: March 2023

Commensal protists and gut bacterial communities exhibit complex relationships, mediated at least in part through host immunity. To improve our understanding of this tripartite interplay, we investigated community and functional dynamics between the murine protistTritrichomonas musculus(T. mu) and intestinal bacteria in healthy and B cell-deficient mice. We identified dramatic, protist-driven remodeling of resident microbiome growth and activities, in parallel withT. mufunctional changes, accelerated in the absence of B cells. Metatranscriptomic data revealed nutrient-based competition between bacteria and the protist. Single cell transcriptomics identified distinctT. mulife stages, providing new evidence for trichomonad sexual replication and the formation of pseudocysts. Unique cell states were validatedin situthrough microscopy and flow cytometry. Our results reveal complex microbial dynamics during the establishment of a commensal protist in the gut, and provide valuable datasets to drive future mechanistic studies.
Local Ancestry Inference for Complex Population Histories
Authors: Pearson Alice , Durbin Richard
Published: March 2023

It 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

The 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

Over 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

The 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

One 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

Modern 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

Axon 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

The 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 Statement

The 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

Background

Recent 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.

Methods

In 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.

Results

Here, 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.

Conclusions

These 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.

Highlights

The 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.
Modelling the structural disorder in trigonal-prismatic coordinated transition metal dichalcogenides
Authors: Ursi Federica , Virga Simone , Pipitone Candida , Sanson Alessandra , Longo Alessandro , Giannici Francesco , Martorana Antonino
Published: March 2023

Trigonal-prismatic coordinated transition metal dichalcogenides (TMDCs) are formed from stacked (chalcogen)–(transition metal)–(chalcogen) triple layers, where the chemical bond is covalent within the triple layers and van der Waals (vdW) forces are effective between the layers. Bonding is at the origin of the great interest in these compounds, which are used as 2D materials in applications such as catalysis, electronics, photoelectronics, sensors, batteries and thermoelectricity. This paper addresses the issue of modelling the structural disorder in multilayer TMDCs. The structural model takes into account stacking faults, correlated displacement of atoms and average crystallite size/shape, and is assessed by simulation of the X-ray diffraction pattern and fitting to the experimental data relative to a powdered sample of MoS2 exfoliated and restacked via lithiation. From fitting, an average crystallite size of about 50 Å, nearly spherical crystallites and a definite probability of deviation from the fully eclipsed atomic arrangement present in the ordered structure are determined. The increased interlayer distance and correlated intralayer and interlayer atomic displacement are attributed to the presence of lithium intercalated in the vdW gap between triple layers (Li/Mo molar ratio of about 0.06). The model holds for the whole class of trigonal-prismatic coordinated TMDCs, and is suitably flexible to take into account different preparation routes.
Syntheses and crystal structures of three novel oxalate coordination compounds: Rb2Co(C2O4)2·4H2O, Rb2CoCl2(C2O4) and K2Li2Cu(C2O4)3·2H2O
Authors: Clulow Rebecca , Lightfoot Philip
Published: March 2023

Single crystals of three novel transition-metal oxalates, dirubidium diaquadioxalatocobalt(II) dihydrate or dirubidium cobalt(II) bis(oxalate) tetrahydrate, Rb2[Co(C2O4)2(H2O)2]·2H2O, (I), catena-poly[dirubidium [[dichloridocobalt(II)]-μ-oxalato]] or dirubidium cobalt(II) dichloride oxalate, {Rb2[CoCl2(C2O4)]}
n
, (II), and poly[dipotassium [tri-μ-oxalato-copper(II)dilithium] dihydrate] or dipotassium dilithium copper(II) tris(oxalate) dihydrate, {K2[Li2Cu(C2O4)3]·2H2O}
n
, (III), have been grown under hydrothermal conditions and their crystal structures determined using single-crystal X-ray diffraction. The structure of (I) exhibits isolated octahedral [Co(C2O4)2(H2O)2] units, whereas (II) consists of trans chains of Co2+ ions bridged by bidentate oxalato ligands and (III) displays a novel tri-periodic network of Li+ and Cu2+ ions linked by oxalato bridging ligands.
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

Purpose

This 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.

Findings

The 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/implications

This study focuses on the mathematical modeling of a multiperiod production-distribution formulation for a closed-loop supply chain.

Originality/value

The 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

Purpose

Corporate 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/approach

This 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.

Findings

This 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/value

In 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

Purpose

Intelligent 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/approach

Two 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).

Findings

In 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/value

This 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

Emulsions 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.
Environmental DNA phylogeography: Successful reconstruction of phylogeographic patterns of multiple fish species from cups of water
Authors: Tsuji Satsuki , Shibata Naoki , Inui Ryutei , Nakao Ryohei , Akamatsu Yoshihisa , Watanabe Katsutoshi
Published: March 2023

Phylogeography is an integrative field of science linking micro‐ and macro‐evolutionary processes, contributing to the inference of vicariance, dispersal, speciation, and other population‐level processes. Phylogeographic surveys usually require considerable effort and time to obtain numerous samples from many geographical sites covering the distribution range of target species; this associated high cost limits their application. Recently, environmental DNA (eDNA) analysis has been useful not only for detecting species but also for assessing genetic diversity; hence, there has been growing interest in its application to phylogeography. As the first step of eDNA‐based phylogeography, we examined (1) data screening procedures suitable for phylogeography and (2) whether the results obtained from eDNA analysis accurately reflect known phylogeographic patterns. For these purposes, we performed quantitative eDNA metabarcoding using group‐specific primer sets in five freshwater fish species belonging to two taxonomic groups from a total of 94 water samples collected from western Japan. As a result, three‐step data screening based on the DNA copy number of each haplotype detected successfully eliminated suspected false positive haplotypes. Furthermore, eDNA analysis could almost perfectly reconstruct the phylogenetic and phylogeographic patterns obtained for all target species with the conventional method. Despite existing limitations and future challenges, eDNA‐based phylogeography can significantly reduce survey time and effort and is applicable for simultaneous analysis of multiple species in single water samples. eDNA‐based phylogeography has the potential to revolutionize phylogeography.
Rates of adherence to cancer treatment guidelines in Australia and the factors associated with adherence: A systematic review
Authors: Bierbaum Mia , Rapport Frances , Arnolda Gaston , Tran Yvonne , Nic Giolla Easpaig Brona , Ludlow Kristiana , Clay‐Williams Robyn , Austin Elizabeth , Laginha Bela , Lo Chi Yhun , Churruca Kate , van Baar Lieke , Hutchinson Karen , Chittajallu Renuka , Owais Syeda Somyyah , Nullwala Ruqaiya , Hibbert Peter , Fajardo Pulido Diana , Braithwaite Jeffrey
Published: March 2023

Adherence to cancer treatment clinical practice guidelines (CPGs) varies enormously across Australia, despite being associated with improved patient outcomes. This systematic review aims to characterize adherence rates to active‐cancer treatment CPGs in Australia and related factors to inform future implementation strategies. Five databases were systematically searched, abstracts were screened for eligibility, a full‐text review and critical appraisal of eligible studies performed, and data extracted. A narrative synthesis of factors associated with adherence was conducted, and the median adherence rates within cancer streams calculated. A total of 21,031 abstracts were identified. After duplicates were removed, abstracts screened, and full texts reviewed, 20 studies focused on adherence to active‐cancer treatment CPGs were included. Overall adherence rates ranged from 29% to 100%. Receipt of guideline recommended treatments was higher for patients who were younger (diffuse large B‐cell lymphoma [DLBCL], colorectal, lung, and breast cancer); female (breast and lung cancer), and male (DLBCL and colorectal cancer); never smokers (DLBCL and lung cancer); non‐Indigenous Australians (cervical and lung cancer); with less advanced stage disease (colorectal, lung, and cervical cancer), without comorbidities (DLBCL, colorectal, and lung cancer); with good‐excellent Eastern Cooperative Oncology Group performance status (lung cancer); living in moderately accessible places (colon cancer); and; treated in metropolitan facilities (DLBLC, breast and colon cancer). This review characterized active‐cancer treatment CPG adherence rates and associated factors in Australia. Future targeted CPG implementation strategies should account for these factors, to redress unwarranted variation particularly in vulnerable populations, and improve patient outcomes (Prospero number: CRD42020222962).
Effect of disturbance on bird feeding guilds in a West African dry forest
Authors: Yilangai R. M. , Abalaka J. , Nsor C. A. , Babale A. , Karau S. D. , Ivande S.
Published: March 2023

West African birds have been declining due to intensive deforestation, yet how bird communities respond to such habitat modification remains understudied in this region. We used point transects to survey bird species in the undisturbed and disturbed edges of Tula Mountains Woodland (TMW), in order to examine responses of bird feeding guilds to disturbance. We found significantly more species in the disturbed than in the undisturbed sites. Number of insectivores was significantly higher than other feeding guilds, followed by the granivores, while nectarivores were the fewest. The lack of variation in mean species richness of bird feeding guilds per timed count between habitats indicates that members of all feeding guilds were widespread across the two habitats. However, the higher species numbers of the carnivores and granivores in the disturbed habitat, and the insectivores in the undisturbed habitat suggest their potential affinities for these habitat scenarios. On the other hand, one‐third of the frugivores and nectarivores utilised the two habitat types, indicating generalist behaviour. Our results suggest that disturbance was not as intensive as to cause significant changes in composition of bird feeding guilds at TMW, but increase in disturbance can potentially have adverse effects on the insectivores, as evidenced in their decreased number of species in the disturbed edges.