bluuebunny/crossref_metadata_2025_split huggingface dataset:
PvDBPII-Matrix M elicits polyfunctional antibodies that limit parasite growth in a challenge trial
Authors: Martinez Francisco J. , White Michael , Guillotte-Blisnick Micheline , Huon Christèle , Boucharlat Alix , Agou Fabrice , England Patrick , Popovici Jean , Hou Mimi M. , Silk Sarah E. , Barrett Jordan R. , Nielsen Carolyn M. , Reimer Jenny M. , Mukherjee Paushali , Chauhan Virander S. , Minassian Angela M. , Draper Simon J. , Chitnis Chetan E. 
Published: August 2023

AbstractThe receptor-binding domain, region II, ofPlasmodium vivaxDuffy binding protein (PvDBPII) binds the Duffy antigen on reticulocytes to mediate invasion. A heterologous vaccine challenge trial recently showed that a delayed dosing regimen with recombinant PvDBPII SalI formulated with adjuvant Matrix-MTMreduced thein vivoparasite multiplication rate (PMR) challenged with theP. vivaxThai isolate PvW1. We describe extensive analysis of the polyfunctional antibody responses elicited by PvDBPII immunization and identify immune correlates for PMR reduction. A classification algorithm identified antibody features that contribute significantly to PMR reduction. These included antibody titre, receptor-binding inhibitory titre, dissociation constant for PvDBPII-antibody interaction, complement C1q and Fc gamma receptor binding and specific IgG subclasses. These data suggest that multiple immune mechanisms elicited by PvDBPII immunization are associated with protection. The identified immune correlates could guide the development of an effective vaccine forP. vivaxmalaria. Importantly, all the polyfunctional antibody features that correlated with protection cross-reacted with both PvDBPII SalI and PvW1 variants, suggesting that immunization with PvDBPII should protect against diverseP. vivaxisolates.
Strong immunogenicity & protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functional polymer
Authors: Sood Subeena , Matar Majed M. , Kim Jessica , Kinsella Meredyth , Rayavara Kempaiah , Signer Olivia , Henderson John , Rogers Joseph , Chawla Bhavna , Narvaez Brandon , Van Ry Alex , Kar Swagata , Arnold Austin , Rice Jennifer S. , Smith Alanna M. , Su Daishui , Sparks Jeff , Goff Corinne Le , Boyer Jean D. , Anwer Khursheed 
Published: August 2023

AbstractDNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90% along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted.
Structure of an open KATPchannel reveals tandem PIP2binding sites mediating the Kir6.2 and SUR1 regulatory interface
Authors: Driggers Camden M. , Kuo Yi-Ying , Zhu Phillip , ElSheikh Assmaa , Shyng Show-Ling 
Published: August 2023

AbstractATP-sensitive potassium (KATP) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. KATPchannel opening is stimulated by PIP2and inhibited by ATP. Mutations that increase channel opening by PIP2reduce ATP inhibition and cause neonatal diabetes. Although considerable evidence has implicated a role for PIP2in KATPchannel function, previously solved open-channel structures have lacked bound PIP2, and mechanisms by which PIP2regulates KATPchannels remain unresolved. Here, we report cryoEM structure of a KATPchannel harboring the neonatal diabetes mutation Kir6.2-Q52R, bound to natural C18:0/C20:4 long-chain PI(4,5)P2in open conformation. The structure reveals two adjacent PIP2molecules between SUR1 and Kir6.2. The first PIP2binding site is conserved among PIP2-gated Kir channels. The second site forms uniquely in KATPat the interface of Kir6.2 and SUR1. Functional studies demonstrate both binding sites determine channel activity. Kir6.2 pore opening is associated with a twist of the Kir6.2 cytoplasmic domain and a rotation of the N-terminal transmembrane domain of SUR1, which widens the inhibitory ATP binding pocket to disfavor ATP binding. The open conformation is particularly stabilized by the Kir6.2-Q52R residue through cation-π bonding with SUR1 - W51. Together, these results uncover the cooperation between SUR1 and Kir6.2 in PIP2binding and gating, explain the antagonistic regulation of KATPchannels by PIP2and ATP, and provide the mechanism by which Kir6.2-Q52R stabilizes an open channel to cause neonatal diabetes.
Wheat bZIPC1 interacts with FT2 and contributes to the regulation of spikelet number per spike
Authors: Glenn Priscilla , Woods Daniel P. , Zhang Junli , Gabay Gilad , Odle Natalie , Dubcovsky Jorge 
Published: August 2023

AbstractLoss-of-function mutations and natural variation in the geneFLOWERING LOCUS T2(FT2) in wheat have previously been shown to affect spikelet number per spike (SNS). However, while other FT-like wheat proteins interact with bZIP-containing transcription factors from the A-group, FT2 does not interact with any of them. In this study, we used a yeast-two-hybrid screen with FT2 as bait and identified a grass-specific bZIP-containing transcription factor from the C-group, designated here as bZIPC1. Within the C-group, we identified four clades including wheat proteins that show Y2H interactions with different sets of FT-like and CEN-like encoded proteins.bZIPC1andFT2expression partially overlap in the developing spike, including the inflorescence meristem. Combined loss-of-function mutations inbZIPC-A1andbZIPC-B1(bzipc1) in tetraploid wheat resulted in a drastic reduction in SNS with a limited effect on heading date. Analysis of natural variation in thebZIPC-B1(TraesCS5B02G444100) region revealed three major haplotypes (H1-H3), with the H1 haplotype showing significantly higher SNS, grain number per spike and grain weight per spike than both the H2 and H3 haplotypes. The favorable effect of the H1 haplotype was also supported by its increased frequency from the ancestral cultivated tetraploids to the modern durum and common wheat varieties. We developed markers for the two non-synonymous SNPs that differentiate thebZIPC-B1ballele in the H1 haplotype from the ancestralbZIPC-B1aallele present in all other haplotypes. These diagnostic markers are useful tools to accelerate the deployment of the favorablebZIPC-B1ballele in pasta and bread wheat breeding programs.Key MessageThe wheat transcription factor bZIPC1 interacts with FT2 and affects spikelet and grain number per spike. We identified a natural allele with positive effects on these two economically important traits.
Regulatory features aid interpretation of 3’UTR Variants
Authors: Romo Lindsay , Findlay Scott D. , Burge Christopher B. 
Published: August 2023

ABSTRACTOur ability to determine the clinical impact of variants in 3’ untranslated regions (UTRs) of genes remains poor. We provide a thorough analysis of 3’UTR variants from several datasets. Variants in putative regulatory elements including RNA-binding protein motifs, eCLIP peaks, and microRNA sites are up to 16 times more likely than other variants to have gene expression and phenotype associations. Heterozygous variants in regulatory motifs result in allele-specific protein binding in cell lines and allele-specific gene expression differences in population studies. In addition, variants in shared regions of alternatively polyadenylated isoforms and those proximal to polyA sites are more likely to affect gene expression and phenotype. Finally, pathogenic 3’UTR variants in ClinVar are 20 times more likely than benign variants to fall in a regulatory site. We incorporated these findings into RegVar, a software tool that interprets regulatory elements and annotations for any 3’UTR variant, and predicts whether the variant is likely to affect gene expression or phenotype. This tool will help prioritize variants for experimental studies and identify pathogenic variants in patients.
Patient iPSC models reveal glia-intrinsic phenotypes in multiple sclerosis
Authors: Clayton Benjamin L.L. , Barbar Lilianne , Sapar Maria , Rusielewicz Tomasz , Kalpana Kriti , Migliori Bianca ,   The NYSCF Global Stem Cell Array® Team, Paull Daniel , Brenner Katie , Moroziewicz Dorota , Sand Ilana Katz , Casaccia Patrizia , Tesar Paul J. , Fossati Valentina 
Published: August 2023

SummaryMultiple sclerosis (MS) is considered an inflammatory and neurodegenerative disease of the central nervous system, typically resulting in significant neurological disability that worsens over time. While considerable progress has been made in defining the immune system’s role in MS pathophysiology, the contribution of intrinsic CNS-cell dysfunction remains unclear. Here, we generated the largest reported collection of iPSC lines from people with MS spanning diverse clinical subtypes and differentiated them into glia-enriched cultures. Using single-cell transcriptomic profiling, we observed several distinguishing characteristics of MS cultures pointing to glia-intrinsic disease mechanisms. We found that iPSC-derived cultures from people with primary progressive MS contained fewer oligodendrocytes. Moreover, iPSC-oligodendrocyte lineage cells and astrocytes from people with MS showed increased expression of immune and inflammatory genes that match those of glial cells from MS postmortem brains. Thus, iPSC-derived MS models provide a unique platform for dissecting glial contributions to disease phenotypes independent of the peripheral immune system and identify potential glia-specific targets for therapeutic intervention.
BrrRCO, encoding a homeobox protein, is involved in leaf lobe development inBrassica rapa
Authors: Li Pan , Su Tongbing , Wu Yudi , Li Hui , Wang Limin , Zhang Fenglan , Yu Shuancang , Wang Zheng 
Published: August 2023

SummaryLeaf shape is a vital economic and developmental trait in leafy vegetable Chinese cabbage (Brassica rapaL.subsp. pekinensis), which varies from smooth to deeply lobed, whereas the molecular basis remains unclear. Here, we detected an incompletely dominant major quantitative trait locus (QTL)qBrrLLA10for the lobed-leaf trait inB. rapa, and identifiedBrrRCO, encoding a HD-Zip transcription factor, as the casual gene underlying lobed leaf formation inB. rapa.Genotyping analysis showed that abundant variations in promoter ofBrrRCOis responsible for leaf lobe variation, and the expression levels and promoter activity were significantly affected by the promoter variations between two parents. BrrRCO was a nucleus-specific protein and possess highest expression level at the bases of each lobe. Ectopic overexpression ofBrrRCOinArabidopsisled to deeply lobed leaves have never been seen in wild type, and leaf lobe development was blocked whenBrrRCOexpression was down-regulated through virus-induced gene silencing assays. Taken together, our findings revealed thatBrrRCOpositively regulate leaf lobe formation in Chinese cabbage, and the cis-regulatory element modifications result in functional variation ofBrrRCO, providing a novel insight into the leaf shape improvement in Chinese cabbage and otherBrassicaspecies.HighlightBrrRCOis essential for leaf lobe formation by repressing local growth of leaf margin cells inB. rapa, and cis-regulatory modifications cause the different allele effects.
Retrotransposon addiction promotes centromere function via epigenetically activated small RNAs
Authors: Shimada Atsushi , Cahn Jonathan , Ernst Evan , Lynn Jason , Grimanelli Daniel , Henderson Ian , Kakutani Tetsuji , Martienssen Robert A. 
Published: August 2023

AbstractRetrotransposons have invaded eukaryotic centromeres in cycles of repeat expansion and purging, but the function of centromeric retrotransposons, if any, has remained unclear. InArabidopsis, centromericATHILAretrotransposons give rise to epigenetically activated short interfering RNAs (easiRNAs) in mutants inDECREASE IN DNA METHYLATION1 (DDM1), which promote histone H3 lysine-9 di-methylation (H3K9me2). Here, we show that mutants which lose both DDM1 and RNA dependent RNA polymerase (RdRP) have pleiotropic developmental defects and mis-segregation of chromosome 5 during mitosis. Fertility defects are epigenetically inherited with the centromeric region of chromosome 5, and can be rescued by directing artificial small RNAs to a single family ofATHILA5retrotransposons specifically embedded within this centromeric region. easiRNAs and H3K9me2 promote pericentromeric condensation, chromosome cohesion and proper chromosome segregation in mitosis. Insertion ofATHILAsilences transcription, while simultaneously making centromere function dependent on retrotransposon small RNAs, promoting the selfish survival and spread of centromeric retrotransposons. Parallels are made with the fission yeastS. pombe, where chromosome segregation depends on RNAi, and with humans, where chromosome segregation depends on both RNAi and HELLSDDM1.
MIR319Cand its targetJAW-TCPs repress each other and establish cell proliferation pattern in incipient leaf primordia inArabidopsis thaliana
Authors: Shankar Naveen , Sunkara Preethi , Nath Utpal 
Published: August 2023

AbstractThe microRNA miR319 and its target JAW-TCP transcription factors regulate leaf morphogenesis in diverse plant species. In young Arabidopsis leaf primordia,JAW-TCPs are detected towards the distal region whereasMIR319Cis expressed at the base. Little is known about how this complementary expression pattern ofMIR319CandJAW-TCPsis generated. Here, we show thatMIR319Cis initially expressed uniformly throughout the incipient primordia and is later abruptly down-regulated at the distal region, with concomitant distal appearance ofJAW-TCPs, when leaves grow to ∼100 µm long. Loss ofJAW-TCPscauses distal extension ofMIR319Cexpression domain, whereas ectopic TCP activity restrictsMIR319Cmore proximally. JAW-TCPs are recruited to and are capable of depositing histone H3K27me3 repressive marks on theMIR319Cchromatin.JAW-TCPs fail to repressMIR319Cin transgenic seedlings where the TCP-bindingcis-elements onMIR319Care mutated, causing miR319 gain-of-function-like phenotype. Based on these results, we propose a model for growth patterning in leaf primordia whereinMIR319Cand JAW-TCPs repress each other and divide the uniformly growing primordia into distal differentiation zone and proximal proliferation domain.Summary statementJAW-TCPstranscriptionally repress the microRNA319 encoding geneMIR319Cto generate their mutually exclusive expression pattern and establish growth polarity during early stages of Arabidopsis leaf primordia.
Sex-specific adaptations to VTA circuits following subchronic stress
Authors: Bouarab Chloé , Wynalda Megan , Thompson Brittney V. , Khurana Ambika , Cody Caitlyn R. , Kisner Alexandre , Polter Abigail M. 
Published: August 2023

AbstractDysregulation of the mesolimbic reward circuitry is implicated in the pathophysiology of stress-related illnesses such as depression and anxiety. These disorders are more frequently diagnosed in females, and sex differences in the response to stress are likely to be one factor that leads to enhanced vulnerability of females. In this study, we use subchronic variable stress (SCVS), a model in which females are uniquely vulnerable to behavioral disturbances, to investigate sexually divergent mechanisms of regulation of the ventral tegmental area by stress. Using slice electrophysiology, we find that female, but not male mice have a reduction in theex vivofiring rate of VTA dopaminergic neurons following SCVS. Surprisingly, both male and female animals show an increase in inhibitory tone onto VTA dopaminergic neurons and an increase in the firing rate of VTA GABAergic neurons. In males, however, this is accompanied by a robust increase in excitatory synaptic tone onto VTA dopamine neurons. This supports a model by which SCVS recruits VTA GABA neurons to inhibit dopaminergic neurons in both male and female mice, but males are protected from diminished functioning of the dopaminergic system by a compensatory upregulation of excitatory synapses.
Scholar's policy recommendations for open innovation in SMEs: a systematic literature review
Authors: Idrissi Fakhreddine Moulay Othman , Castonguay Yan 
Published: August 2023

PurposeSmall and medium-sized enterprises (SMEs) are currently showing an increasingly open innovation (OI) approach. Public policies supporting the adoption of OI by SMEs are becoming a priority for policymakers. Therefore, the aim of this article is to contribute to the literature by mapping scholars' policy recommendations for implementing OI among SMEs.Design/methodology/approachThe authors conducted a systematic review of the literature (SRL) on the topic to achieve this purpose. A total of 99 academic articles were selected from the Web of Science and Scopus databases to suggest the main scholars' policy recommendations to implement OI among SMEs.FindingsResults indicated that scholars' policy recommendations for OI adoption in SMEs can be organized into: research and development (R&D), networking, collaboration, knowledge and intellectual property rights (IPR), ecosystem, managerial capabilities, funding and incentives and sustainability policies.Research limitations/implicationsOnly relevant articles about this topic have been included due to the reliance on the interpretations of the authors. The analysis of the literature revealed that the authors did not always distinguish policies dedicated to SMEs and those dedicated to large companies. Moreover, policies are not matched according to each OI dimensions (e.g. inbound, outbound and coupled OI).Originality/valueThe article uses a systematic literature review method that combines qualitative and quantitative analyses. This method contributes to theoretical development of OI policies dedicated, in particular to SMEs. This paper also provides policymakers and researchers with insights on the scope of OI policies that could support economic growth.
Historical effect of verified purchases and ordinary users’ testimonials on the sales rank of experience and search goods
Authors: Sajedikhah Ali , Rezaei Dolatabadi Hossein , Shahin Arash 
Published: August 2023

Purpose
This study aims to investigate the extent and pattern of the influence of one of the most important decision-making tools in the context of social commerce. This study demonstrates how much customer testimonials (including verified purchases and ordinary users) can influence the sales rank of experience and search goods.

Design/methodology/approach
The data were collected by text mining and performing a content analysis on the XML documents of Web pages and processing them. For search goods, 22,311 opinions were recorded regarding 95 mobile phones. Additionally, for experience goods, 67,817 opinions were recorded regarding 162 books in the Amazon online store. The data were analyzed by functional regression method in longitudinal data analysis.

Findings
In terms of importance, the opinions and recommendations of verified purchases had a 60% greater impact on the sales rank of experience goods than the opinions and recommendations of ordinary users. In search goods, the opinions of ordinary users had a greater impact than the opinions of verified purchases. The historical effect of the opinions of ordinary users at the end of the review period on sales rank was evident, while the historical effect of the verified purchase viewpoints during the review period had a nonlinear curve. The results showed that it was necessary to increase the volume of comments to increase their reliability in experience goods.

Practical implications
Measuring the effect of customer testimonials helps the managers of retail websites design algorithms and online suggestion systems, thereby improving the sales of their products by providing information desired by customers.

Social implications
Individuals can be a source of information and influence the buying decision process of others by sharing their experiences. This issue helps reduce the purchase risk and explains the importance of interaction and sharing the customer’s experience.

Originality/value
Analyzing the impact of customer testimonials by separating verified purchases and ordinary users is one of the advantages of this study. The quantitative estimation of the impact of recommendations and the provision of a model of their historical effect is one of the approaches not addressed in similar studies.
Organizational structure and dynamic capabilities on business model innovation in project-driven enterprises: evidence from the construction industry
Authors: Wang Dan , Huang Ruopeng , Li Kaijian , Shrestha Asheem 
Published: August 2023

PurposeFlexibility and efficiency are dual attributes of the organizational structure that are crucial for project-driven enterprises to achieve sustainable development in a dynamic environment. However, there is a lack of research on the patterns by which the dual attributes of a project-driven enterprise’s organizational structure affect business model innovation. Employing organizational theory, this study aims to assess the mediating mechanisms and dynamic capabilities through which the dual attributes of the organizational structure influence business model innovation in project-driven enterprises.Design/methodology/approachData were collected from 242 employees from four project-driven companies across 26 cities (e.g. Beijing, Tianjin, Guangzhou and Shenzhen) in China. Structural equation modeling revealed the relationship between organizational structure’s dual attributes and business model innovation.FindingsThe findings show that the dual attributes (flexibility and efficiency) of the organizational structure have positive impacts on business model innovation. Moreover, dynamic capabilities mediate the relationship between the dual attributes and business model innovation in project-driven enterprises.Originality/valueThis study provides contributions to innovation research in the context of project-driven enterprises by revealing the influence of organizational structure on business model innovation through the firms’ dynamic capabilities. Such knowledge can enable managers of project-driven enterprises to develop effective interventions to promote business model innovation.