bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel exotic alleles of EARLY FLOWERING 3 determine plant development in barley
Authors: Zahn Tanja , Zhu Zihao , Ritoff Niklas , Krapf Jonathan , Junker Astrid , Altmann Thomas , Schmutzer Thomas , Tüting Christian , Kastritis Panagiotis L. , Babben Steve , Quint Marcel , Pillen Klaus , Maurer Andreas 
Published: July 2022

AbstractEARLY FLOWERING 3(ELF3) is an important regulator of various physiological and developmental processes and hence may serve to improve plant adaptation which will be substantial for future plant breeding. To expand the limited knowledge on barleyELF3in determining agronomic traits, we conducted field studies with heterogeneous inbred families (HIFs) derived from selected lines of the wild barley nested association mapping population HEB-25. During two growing seasons, phenotypes of nearly isogenic HIF sister lines, segregating for exotic and cultivated alleles at theELF3locus, were compared for ten developmental and yield-related traits. We determine novel exoticELF3alleles and show that HIF lines, carrying the exoticELF3allele, accelerated plant development compared to the cultivatedELF3allele, depending on the genetic background. Remarkably, the most extreme phenotypic effects could be attributed to one exoticELF3allele, differing in only one SNP from the cultivated BarkeELF3allele. This SNP causes an amino acid change, which predictively has an impact on the protein structure of ELF3, thereby possibly affecting phase separation behaviour and nano-compartment formation of ELF3 and, potentially, also affecting its local cellular interactions causing significant trait differences between HIF sister lines.
Mapping PTBP splicing in human brain identifies targets for therapeutic splice switching including SYNGAP1
Authors: Dawicki-McKenna Jennine M. , Felix Alex J. , Waxman Elisa A. , Cheng Congsheng , Amado Defne A. , Ranum Paul T. , Bogush Alexey , Dungan Lea V. , Heller Elizabeth A. , French Deborah L. , Davidson Beverly L. , Prosser Benjamin L. 
Published: July 2022

AbstractAlternative splicing of neuronal genes is controlled in part by the coordinated action of the polypyrimidine tract binding proteins (PTBP1 and PTBP2). While PTBP1 is ubiquitously expressed, PTBP2 is predominantly neuronal, controlling the expression of such targets as DLG4, which encodes PSD95, a protein important in synaptic function whose deficiency causes neurodevelopmental disorders. Here, we fully define the PTBP2 footprint in the human transcriptome using both human brain tissue and neurons derived from human induced pluripotent stem cells (iPSC-neurons). We identify direct PTBP2 binding sites and define PTBP2-dependent alternative splicing events, finding novel targets such as STXBP1 and SYNGAP1, which are synaptic genes also associated with neurodevelopmental disorders. The resultant PTBP2 binding and splicing maps were used to test if PTBP2 binding could be manipulated to increase gene expression in PTBP-targeted genes that cause disease when haploinsufficient. We find that PTBP2 binding to SYNGAP1 mRNA promotes alternative splicing and non-sense mediated decay. Antisense oligonucleotides that disrupt PTBP binding sites on SYNGAP1 redirect splicing and increase gene and protein expression. Collectively, our data provide a comprehensive view of PTBP2-dependent alternative splicing in human neurons and human cerebral cortex, guiding the development of novel therapeutic tools that may benefit a range of neurodevelopmental disorders.
Limitations of Busulfan to Create Humanize Mice with an Innate Immune System
Authors: Alhawiti Ohud , Hu Bin , Kobilinski Jennifer , Guo Chunqing , Landry Joseph W. 
Published: July 2022

AbstractHumanized mouse models have improved biomedical research by providing a tractable system with which to perform in vivo experiments on human tissues. Use of irritators is the standard method for establishing high levels of stem cell engraftment, however not all institutes have access to this instrumentation in the animal facility. The use of busulfan has been successfully used to precondition for stem cell engraftment on a limited number of mouse backgrounds. In this report we further test the utility of busulfan as a means to successfully engraft hIL15-Tg-NSG and SGM3-NSG mouse stains which are capable of establishing the innate NK cell and myeloid immune compartments. Results from our studies show that busulfan can successfully precondition hIL15-Tg-NSG mice but not SGM3-NSG mice for high levels of human immune cell engraftment. SGM3-NSG mice preconditioned with busulfan exhibited only 10-20% human CD45 cells in the bone marrow or spleen, where as NSG and hIL15-Tg-NSG mice routinely achieved ∼80%. Busulfan preconditioned SGM3-NSG mice showed elevated levels of granulocytic MDSC, and cDC1 and cDC2 myeloid populations. This is in contrast with hIL15-TG-NSG which showed robust reconstitution of mature CD16 expressing NK cells. We conclude from our studies that busulfan is an effective means to precondition mice for CD34+ stem cell engraftment, but it may have limitations when use to precondition the SGM3-NSG model.
A Toxin-Antidote Selfish Element Increases Fitness of its Host
Authors: Long Lijiang , Xu Wen , Paaby Annalise B. , McGrath Patrick T. 
Published: July 2022

ABSTRACTSelfish genetic elements can promote their transmission at the expense of individual survival, creating conflict between the element and the rest of the genome. Recently, a large number of toxin-antidote (TA) post-segregation distorters have been identified in non-obligate outcrossing nematodes. Their origin and the evolutionary forces that keep them at intermediate population frequencies are poorly understood. Here, we study a TA element in C. elegans called peel-1/zeel-1. Two major haplotypes of this locus, with and without the selfish element, segregate in C. elegans. Here we study the fitness consequences of the peel-1/zeel-1 element outside of its role in gene drive in non-outcrossing animals. We demonstrate that loss of the toxin peel-1 decreased fitness of hermaphrodites and resulted in reductions in fecundity and body size. This fitness advantage is independent of the antidote zeel-1, suggesting that a distinct peel-1 pathway plays a biological role. This work demonstrates that a TA element can provide a fitness benefit to its hosts, either during their initial evolution or by being co-opted by the animals following their selfish spread. These findings guide our understanding on how TA elements can remain in a population where gene drive is minimized, helping resolve the mystery of prevalent TA elements in selfing animals.
Melanoma cells appropriate pericyte:endothelial cell crosstalk during perivascular invasion in the brain
Authors: Zhang Yu , Riedstra Caroline P. , Wang Sarah , Patel Sonia , Bald Tobias , Kumar Pankaj , Rohani Ali , Kashatus David F. , Moschos Stergios J. , Dudley Andrew C. 
Published: July 2022

AbstractPost brain colonization, cancer cells may adhere to and spread along the abluminal surface of the vasculature providing advantageous access to oxygen, nutrients, and vessel-derived paracrine factors. For example, brain-tropic melanoma cells are well-known to invade along or within blood vessels at the invasive front, but the molecular mechanisms that guide this process are not well-characterized. We have used melanoma cells of different phenotypic states (melanocytic versus mesenchymal) to characterize different modes of perivascular invasion in the brain. We find that Sox9hi mesenchymal state melanoma cells undergo pericyte-like spreading along brain blood vessels via a Snail1-dependent process; in contrast, Sox10hi melanocytic state melanoma form proliferative, perivascular clusters. Snai1 deletion in mesenchymal-state melanoma cells diminishes Tgfβ-induced expression of Pdgfrβ which impairs Tgfβ/Pdgf ligand-driven motility along the brain microvasculature and dramatically reduces perivascular dispersal of melanoma cells throughout the brain post-colonization. These data suggest that, depending on their transcriptional/phenotypic state, some melanoma cells may appropriate signals that typically mediate endothelial cell:pericyte cross talk as an adaptive mechanism for maintaining vessel proximity and motility within the brain microenvironment.
Cortical polarity ensures its own asymmetric inheritance in the stomatal lineage to pattern the leaf surface
Authors: Muroyama Andrew , Gong Yan , Hartman Kensington S. , Bergmann Dominique 
Published: July 2022

AbstractAsymmetric cell divisions (ACDs) specify differential cell fates across kingdoms. In metazoans, preferential inheritance of fate determinants into one daughter cell frequently depends on polarity-cytoskeleton interactions (1, 2). Despite the prevalence of ACDs during plant development, evidence for analogous mechanisms that segregate fate determinants during ACD remain elusive. Here, we describe a mechanism in the Arabidopsis thaliana leaf epidermis that ensures unequal inheritance of a fate-enforcing polarity domain during the creation of stomata, essential two-celled valves that mediate gas exchange between the plant and environment. Formation of a plasma membrane-associated polarity domain, defined by BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL), overrides default division patterns in stomatal precursors. The polarity domain exerts this control by constraining formation of the preprophase band of microtubules that mark the cortical division site and are a hallmark of plant mitosis. Experimentally uncoupling preprophase band establishment from the polarity domain results in aberrant polarity inheritance and subsequent fate errors. Mechanistically, our analyses of the interactions between microtubules and BASL in native and heterologous contexts revealed that the stomatal lineage polarity domain locally depletes cortical microtubules by altering microtubule stability. As the inherited cortical BASL crescent scaffolds a MAPK cascade to suppress progenitor identity in one daughter post-division, we propose that BASL-microtubule interactions represent a novel strategy to link cell identity to division orientation. Together, our data highlight how a common biological module, coupling the cytoskeleton to fate segregation via cell polarity, has been configured to accommodate the unique features of plant development.
Different inhibition of Nrf2 by two Keap1 isoforms α and β to shape malignant behaviour of human hepatocellular carcinoma
Authors: Chen Feilong , Xiao Mei , Feng Jing , Wufur Reziyamu , Liu Keli , Hu Shaofan , Zhang Yiguo 
Published: July 2022

AbstractNrf2 (nuclear factor E2-related factor 2, encoded by Nfe2l2) acts as a master transcriptional regulator in mediating antioxidant, detoxification and cytoprotective responses against oxidative, electrophilic and metabolic stress, but also plays a crucial role in cancer metabolism and multiple oncogenic pathways, whereas the redox sensor Keap1 functions as a predominant inhibitor of Nrf2 and hence changes in its expression abundance directly affect the Nrf2 stability and transcriptional activity. However, nuanced functional isoforms of Keap1α and β have rarely been identified to date. Herein, we have established four distinct cell models stably expressing Keap1-/-, Keap1β (Keap1Δ1-31), Keap1-Restored and Keap1α-Restored, aiming to gain a better understanding of similarities and differences of two Keap1 isoforms between their distinct regulatory profiles. Our experimental evidence revealed that although Keap1 and its isoforms are still localized in the cytoplasmic compartments, they elicited differential inhibitory effects on Nrf2 and its target HO-1. Furtherly, transcriptome sequencing unraveled that they possess similar but different functions. Such functions were further determined by multiple experiments in vivo (i.e. subcutaneous tumour formation in nude mice) and in vitro (e.g., cell cloning, infection, migration, wound healing, cell cycle, apoptosis, CAT enzymatic activity and intracellular GSH levels). Of note, the results obtained from tumorigenesis experiments in xenograft model mice were verified based on the prominent changes in the PTEN signaling to the PI3K-AKT-mTOR pathways, in addition to substantially aberrant expression patterns of those typical genes involved in the EMT (epithelial-mesenchymal transition), cell cycle and apoptosis.
Intralumenal docking of Cx36 channels in the ER isolates mis-trafficked protein
Authors: Tetenborg Stephan , Liss Viktoria , Breitsprecher Leonhard , Timonina Ksenia , Kotova Anna , Acevedo Harnecker Alejandra Jesús , Yuan Chunxu , Shihabeddin Eyad , Dedek Karin , Zoidl Georg , Hensel Michael , O’Brien John 
Published: July 2022

AbstractThe intracellular domains of connexins are essential for the assembly of gap junctions. For connexin 36 (Cx36), the major neuronal connexin, it has been shown that a dysfunctional PDZ binding motif interferes with electrical synapse formation. However, it is still unknown how this motif coordinates the transport of Cx36. In the present study, we characterize a phenotype of Cx36 mutants that lack a functional PDZ binding motif using HEK293T cells as an expression system. We provide evidence that an intact PDZ binding motif is critical for proper ER export of Cx36. Removing the PDZ binding motif of Cx36 results in ER retention and the formation of multi-membrane vesicles containing gap junction-like connexin aggregates. Using a combination of site directed mutagenesis and electron micrographs we reveal that these vesicles consist of Cx36 channels that docked prematurely in the ER. Our data suggest a model in which ER-retained Cx36 channels reshape the ER membrane into concentric whorls that are released into the cytoplasm.
Structural basis for RNA slicing by a plant Argonaute
Authors: Xiao Yao , Maeda Shintaro , Otomo Takanori , MacRae Ian J. 
Published: July 2022

AbstractArgonaute (AGO) proteins use small RNAs to recognize transcripts targeted for silencing in plants and animals. Many AGOs possess an endoribonuclease activity termed RNA slicing, which catalyzes rapid turnover of target RNAs. The nuclease activity of Thermus thermophilus AGO (TtAgo)1,2 is often used as a model for RNA slicing, but how well DNA-guided slicing by this bacterial thermophile resembles RNA-guided slicing by eukaryotic AGOs is not known. We present cryo-EM structures of the Arabidopsis thaliana Argonaute10 (AtAgo10)-guide RNA complex with and without a target RNA representing a slicing substrate. Like TtAgo, AtAgo10 conformation expands in response to target binding. However, the AtAgo10-guide-target complex adopts slicing-competent and -incompetent conformations that are distinct from structures of TtAgo. AtAgo10 slicing activity is licensed by docking target (t) nucleotides t9-t13 into a surface channel containing the AGO endoribonuclease active site. A ß-hairpin, conserved in the L1 domain of eukaryotic AGOs, secures the t9-t13 segment and coordinates t9-t13 docking with extended guide-target pairing, preventing the complex from becoming trapped in slicing-incompetent conformations. Results show the mechanism for achieving RNA slicing in eukaryotes is distinct from that of bacteria and provide insights for controlling small interfering RNA (siRNA) potency.
smalldisco, a pipeline for siRNA discovery and 3’ tail identification
Authors: Caldas Ian V. , Kelley Leanne H. , Ahmed-Braimah Yasir H. , Maine Eleanor M. 
Published: July 2022

AbstractCapturing and sequencing small RNAs is standard practice, however identification of a group of these small RNAs—small interfering RNAs (siRNAs)—has been more difficult. We present smalldisco, a command-line tool forsmallinterfering RNAdiscovery and annotation from small RNA-seq datasets. smalldisco can distinguish short reads that map antisense to an annotated genomic feature (e.g., exons or mRNAs), annotate these siRNAs, and quantify their abundance. smalldisco also uses the program Tailor to quantify 3’ non-templated nucleotides of siRNAs or any small RNA species. smalldisco and supporting documentation are available for download from GitHub (https://github.com/ianvcaldas/smalldisco).
Structure and dynamic association of an assembly platform subcomplex of the bacterial type II secretion system
Authors: Dazzoni Régine , Li Yuanyuan , López-Castilla Aracelys , Brier Sébastien , Mechaly Ariel , Cordier Florence , Haouz Ahmed , Nilges Michael , Francetic Olivera , Bardiaux Benjamin , Izadi-Pruneyre Nadia 
Published: July 2022

AbstractType II secretion systems (T2SS) allow diderm bacteria to secrete hydrolytic enzymes, adhesins or toxins important for growth and virulence. In T2SS, secretion of folded proteins from the periplasm to the cell surface requires assembly of periplasmic filaments called pseudopili. Like the related type IV pili, pseudopili are polymerized in the inner membrane through addition of subunits at the filament base, mediated by the essential assembly platform (AP). To understand the structure and molecular role of the AP, we focused on its components PulL and PulM from the Klebsiella oxytoca T2SS. By combining biophysical methods, NMR and X-ray crystallography we studied the structure and associations of their periplasmic domains. We describe the first structure of the heterodimer complex formed by the PulL and PulM ferredoxin-like domains and show how their structural complementarity and plasticity favor their association during the secretion process. Cysteine scanning and cross-linking of transmembrane segments provided additional constraints to build a structural model of the PulL–PulM complex and assembly in the cellular context. Together with the relative abundance of PulL, PulM and their partners our findings suggest a model of the AP as a dynamic hub that orchestrates pseudopilus polymerization.
Managing strategies for mitigating interacting barriers to sustainable online e-waste collection platforms in India
Authors: Chandra Pratistha , Yeh Chung-Hsing , Dutta Pankaj 
Published: July 2022

PurposeThis study identifies barriers faced by online e-waste collection platforms in India and proposes a novel approach to manage strategies that contribute towards making such online platforms economically, socially, and environmentally sustainable by mitigating their interacting barriers.Design/methodology/approachThe approach consists of a barrier assessment process and a strategy evaluation and planning process. The barrier assessment process uses multiple criteria decision making (MCDM) based method to evaluate the interactive effects of the barriers to derive their direct and indirect impacts on sustainability. The strategy evaluation and planning process evaluates the overall contribution value of strategies for mitigating interacting barriers and then categorizes them into planning zones based on their contribution and feasibility.FindingsThe interaction among the barriers is a significant component of the overall impact of the barriers on sustainability. The most impactful barriers are the lack of dissemination of information, lack of government support, insufficient infrastructure, and awareness and attitude of consumers. Lack of government support is the most influential causal barrier. Lack of information dissemination is a significant causal barrier with the highest overall impact on sustainability. Priority strategies that must be implemented to ensure sustainability include government support, offering higher prices or discounts for giving up e-waste, and increasing information dissemination.Originality/valueDifferent from existing approaches for evaluating sustainability strategies, the strategies in this study are identified and evaluated based on their overall contribution towards mitigating interacting barriers to sustainability. The approach is applied in the Indian context to reveal the most influential barriers to the sustainability of online e-waste collection platforms and the most effective strategies for mitigating these barriers. The outcomes of this study contribute to strategy planning for sustainable online e-waste collection platforms in India.
The framing of plastic pollution responsibility: comparing corporate versus environmental movement discursive evaluations
Authors: Ravazzani Silvia , Maier Carmen Daniela 
Published: July 2022

PurposeThis article aims to investigate evaluative framing of global plastic pollution as discursively performed by two opposed categories of social actors, namely corporations versus environmental movements.Design/methodology/approachThe article builds on the literature related to framing, issue arenas and moral evaluations to unravel how evaluative framing and counterframing are implemented in multimodal digital spaces and how social practices get legitimized or delegitimized according to different communicative purposes. It presents a longitudinal critical discourse analysis of the issue-related webpages and press releases of PepsiCo, one of the worst global plastic polluters, and of the global environmental movement #breakfreefromplastic.FindingsFindings suggest that the systematic recurrence of specific evaluative strategies has a double macro-function: (a) organizing discourses strategically through its presence or absence; (b) signalling the moral significance of recontextualized social practices by conferring legitimacy to remedial actions and/or illegitimacy to deviant actions.Social implicationsThis study contributes to increasing accountable environmental action and trustful communication for overcoming global sustainability issues.Originality/valueThe article offers a nuanced understanding of the role of evaluative framing in communicating global sustainability issues. Methodologically, it extends existing categories of moral evaluations and articulates a framework for future studies.
Boundary-spanning search and business model innovation: the joint moderating effects of innovative cognitive imprinting and environmental dynamics
Authors: Zhu Peiyu , Miao Xiaoming , Jin Shumo 
Published: July 2022

PurposeBusiness model innovation (BMI) is an important channel of enterprise innovation, and BMI's antecedents have attracted extensive attention. The purpose of this paper is to address a substantial gap in the extant literature by developing a moderate model to explain the effects of boundary-spanning search on BMI as well as whether and how innovative cognitive imprinting (ICI) and environmental dynamics (ED) affect the above relationship.Design/methodology/approachA total of 239 usable questionnaires from different enterprises in China were collected to obtain firm-level data. Then multiple regression analyses were used by SPSS software to test hypotheses.FindingsBoundary-spanning search extensity (BSE) and focus have inverted U-shaped impacts on BMI; ICI moderates the relationship between boundary-spanning search and BMI and steepens the curves; ED weakens the moderating role of ICI.Originality/valueBy identifying two antecedents of BMI, this paper contributes to the literature on the antecedents of BMI. Meanwhile, the joint moderating effect of ICI and ED is introduced into the emergent analysis framework of the relationship between boundary-spanning search and BMI and examined through empirical analysis for the first time.