bluuebunny/crossref_metadata_2025_split huggingface dataset:
GluN2B-mediated regulation of silent synapses for receptor specification and addiction memory
Authors: Kim Hyun Jin , Lee Sangjun , Kim Gyu Hyun , Sung Kibong , Yoo Taesik , Pyo Jung Hyun , Jo Hee-Jung , Lee Sanghyeon , Lee Hyun-Young , Jung Jung Hoon , Lee Kea Joo , Kim Joung-Hun 
Published: May 2024

AbstractPsycho-stimulants including cocaine elicit stereotyped, addictive behaviors. Re-emergence of silent synapses containing only NMDA-type glutamate receptors (NMDARs) is a critical mediator of addiction memory and seeking behaviors. Despite the predominant abundance of GluN2B-containing NMDARs in silent synapses, their operational mechanisms are not fully understood. Using conditional depletion/deletion of GluN2B at D1-expressing accumbal medium spiny neurons, we examine the synaptic and behavioral actions that silent synapses incur after repeated exposure to cocaine. GluN2B ablation reduces the proportion of silent synapses, but some of them can persist by substitution to GluN2C, which drives the aberrantly-facilitated synaptic incorporation of calcium-impermeable AMPA-type glutamate receptors (AMPARs). The resultant precocious maturation of silent synapses impairs addiction memory but elevates locomotor activity, which can be normalized by blockade of calcium-impermeable AMPAR trafficking. Collectively, GluN2B supports the competence of cocaine-induced silent synapses for specifying subunit composition of AMPARs, and thereby expression of addition memory and the related behaviors.
Rapid screening and identification of genes involved in bacterial extracellular membrane vesicle production using a curvature-sensing peptide
Authors: Inoue Hiromu , Kawano Kenichi , Kawamoto Jun , Ogawa Takuya , Kurihara Tatsuo 
Published: May 2024

ABSTRACTBacteria secrete extracellular membrane vesicles (EMVs). Physiology and biotechnological applications of these lipid nanoparticles have been attracting significant attention. However, the molecular basis of EMV biogenesis has not yet been fully elucidated. In the previous research, an N-terminus-substituted FAAV peptide labeled with NBD (nFAAV5-NBD) was developed, which can sense a curvature of a lipid bilayer and selectively bind to EMVs in the presence of the cells. Herein, we applied nFAAV5-NBD to a screening of hyper- and hypo-vesiculation transposon mutants of a Gram-negative bacterium,Shewanella vesiculosaHM13, to identify the genes involved in EMV production. As a result, for 16 and six genes, we found that transposon insertion within or near the gene caused hyper- and hypo-vesiculation, respectively. Targeted gene-disrupted mutants of the identified genes demonstrated that the lack of putative dipeptidyl carboxypeptidase, glutamate synthase β-subunit, LapG protease, metallohydrolase, RNA polymerase sigma-54 factor, inactive transglutaminase, PepSY domain-containing protein, and Rhs-family protein caused EMV overproduction. On the other hand, disruption of the genes encoding putative phosphoenolpyruvate synthase, D-hexose-6-phosphate epimerase, NAD-specific glutamate dehydrogenase, and sensory box histidine kinase/response regulator decreased EMV production. This study shows the utility of a novel screening method using a curvature-sensing peptide and fundamental information on the genes related to EMV production.IMPORTANCEConventional methods for isolation and quantification of EMVs are generally time-consuming. nFAAV5-NBD can detect EMVs in the culture without separating EMVs from cells.In situdetection of EMVs using this peptide facilitated screening of the genes related to EMV production. We succeeded in identifying a number of genes involved in the EMV production ofS. vesiculosaHM13, and the strains obtained in this study would contribute to the elucidation of bacterial EMV formation mechanisms. Additionally, the hyper-vesiculating mutants obtained in this study would be useful in the application of this bacterium, such as in the production of useful substances as cargoes of EMVs and in the production of surface-engineered vesicles.
MECOM promotes leukemia progression and inhibits mast cell differentiation through functional competition with GATA2
Authors: Iida Kohei , Nakanishi Mayuko , Nakahara Jakushin , Asada Shuhei , Isobe Tomoya , Yabushita Tomohiro , Ozawa Manabu , Yamada Yasuhiro , Kitamura Toshio , Yamamoto Keita , Goyama Susumu 
Published: May 2024

ABSTRACTMECOM is a nuclear transcription factor essential for the proliferation of hematopoietic stem cells (HSCs) and myeloid leukemia cells. MECOM contains N- and C-terminal zinc finger domains (ZFDs) and binding motifs for the corepressor CtBP to regulate gene expression. Recent studies have shown that germlineMECOMvariants are associated with thrombocytopenia, radioulnar synostosis, and bone marrow failure, collectively termed MECOM-associated syndromes. Although the mutations are clustered in the C-terminal ZFD, how these mutations affect MECOM function has remained unclear. In addition, the individual genes and pathways regulated by MECOM are less well understood. In this study, we showed that the C-terminal ZFD is a major DNA-binding domain of MECOM and that the disease-associated mutations abolish the DNA-binding ability. We also found that MECOM functionally antagonizes GATA2 through the C-terminal ZFD-mediated DNA binding and CtBP interaction, thereby promoting myeloid leukemogenesis while inhibiting mast cell differentiation. Furthermore, we generated mutant MECOM knockin mice harboring a C-terminal ZFD mutation that recapitulate several features of MECOM-associated syndromes, including HSC and B-cell reduction. Our study demonstrates that C-terminal ZFD mutations are loss-of-function mutations with reduced DNA-binding ability, reveals the critical role of MECOM in inhibiting GATA2, and provides a novel mouse model for MECOM-associated syndromes.
Targeted anticancer pre-vinylsulfone covalent inhibitors of carbonic anhydrase IX
Authors: Vaškevičius Aivaras , Baronas Denis , Leitans Janis , Kvietkauskaitė Agnė , Rukšėnaitė Audronė , Manakova Elena , Toleikis Zigmantas , Kaupinis Algirdas , Kazaks Andris , Gedgaudas Marius , Mickevičiūtė Aurelija , Juozapaitienė Vaida , Schiöth Helgi B , Jaudzems Kristaps , Valius Mindaugas , Tars Kaspars , Gražulis Saulius , Meyer-Almes Franz-Josef , Matulienė Jurgita , Zubrienė Asta , Dudutienė Virginija , Matulis Daumantas 
Published: May 2024

ABSTRACTWe designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: 1) primary sulfonamide group recognizing carbonic anhydrases (CA), 2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and 3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification. Our designed prodrug candidates bearing moderately active pre-vinyl sulfone esters or weakly active carbamates optimized for mild covalent modification activity to avoid toxic non-specific modifications and selectively target CAIX. The lead inhibitors reached 2 pM affinity, highest among known CAIX inhibitors. The strategy could be used for any disease drug target protein bearing a His residue in the vicinity of the active site.
The buoyancy of cryptococcal cells and its implications for transport and persistence ofCryptococcusin aqueous environments
Authors: Jimenez Isabel A. , Stempinski Piotr R. , Dragotakes Quigly , Greengo Seth D. , Sanchez Ramirez Lia , Casadevall Arturo 
Published: May 2024

AbstractCryptococcusis a genus of saprophytic fungi with global distribution. Two species complexes,C. neoformansandC. gattii, pose health risks to humans and animals. Cryptococcal infections result from inhalation of aerosolized spores and/or desiccated yeasts from terrestrial reservoirs such as soil, trees, and avian guano. More recently,C. gattiihas been implicated in infections in marine mammals, suggesting that inhalation of liquid droplets or aerosols from the air-water interface is also an important, yet understudied, mode of respiratory exposure. Water transport has also been suggested to play a role in the spread ofC. gattiifrom tropical to temperate environments. However, the dynamics of fungal survival, persistence, and transport via water have not been fully studied. The size of the cryptococcal capsule was previously shown to reduce cell density and increase buoyancy. Here, we demonstrate that cell buoyancy is also impacted by the salinity of the media in which cells are suspended, with formation of a halocline interface significantly slowing the rate of settling of cryptococcal cells through water, resulting in persistence ofC. neoformanswithin 1 cm of the air-water interface for over 60 min andC. gattiifor 4-6 h. Our data also showed that during culture in yeast peptone dextrose media (YPD), polysaccharide accumulating in the supernatant formed a raft that augmented buoyancy and further slowed settling of cryptococcal cells. These findings illustrate new mechanisms by which cryptococcal cells may persist in aquatic environments, with important implications for aqueous transport and pathogen exposure.ImportanceCryptococcosis is a major fungal disease leading to morbidity and mortality worldwide.C. neoformansis a major fungal species of public health concern, causing opportunistic systemic infections in immunocompromised patients.C. gattiiwas traditionally a tropical pathogen, but in the 1990s emerged in the temperate climates of British Columbia and the Pacific Northwest United States. Outbreaks in these areas also led to the first host record of cryptococcosis in free-ranging cetaceans.C. gattiiis particularly concerning as an emerging fungal pathogen due to its capacity to cause clinical disease in immunocompetent patients, its recent spread to a new ecological niche, and its higher resistance to antifungal therapies. Our research defines characteristics that influence transport of cryptococci through water and its persistence at the air-water interface, which improve our understanding of mechanisms for cryptococcal aqueous transport and persistence.
Landscape of Evolutionary Arms Races between Transposable Elements and KRAB-ZFP Family
Authors: Kosuge Masato , Ito Jumpei , Hamada Michiaki 
Published: May 2024

AbstractTransposable elements (TEs) are mobile parasitic sequences that have expanded within the host genome. It has been hypothesized that host organisms have expanded the Krüppel-associated box-containing zinc finger proteins (KRAB-ZFPs), which epigenetically suppress TEs, to counteract disorderly TE transpositions. This process is referred to as the evolutionary arms race. However, the extent to which this evolutionary arms race occurred across various TE families remains unclear. In the present study, we systematically explored the evolutionary arms race between TE families and KRAB-ZFPs using public ChIP-seq data. We discovered and characterized new instances of evolutionary arms races with KRAB-ZFPs in endogenous retroviruses. Furthermore, we found that the regulatory landscape shaped by this arms race contributed to the gene regulatory network. In summary, our results provide insight into the impact of the evolutionary arms race on TE families, the KRAB-ZFP family, and host gene regulatory networks.
Genomic analyses inDrosophilado not support the classic allopatric model of speciation
Authors: Yusuf Leeban H. , Laetsch Dominik R. , Lohse Konrad , Ritchie Michael G. 
Published: May 2024

AbstractThe allopatric model of speciation has dominated our understanding of speciation biology and biogeography since the Modern Synthesis. It is uncontroversial because the cessation of gene flow during allopatry will allow reproductive isolation to readily emerge as a by-product of evolutionary divergence. However, whether allopatric speciation is common has rarely been systematically tested across a continuum of closely-related species. Here, we fit a range of demographic models of evolutionary divergence to whole-genome sequence data from 93 pairs ofDrosophilaspecies to infer speciation histories and levels of post-divergence gene flow. We find that speciation with gene flow is common, even between currently allopatric pairs of species. Estimates of historical gene flow are not predicted by current range overlap, nor is there convincing support that secondary contact commonly leads to the cessation of gene flow as predicted by models of reinforcement. Instead, our analyses suggest that most speciation processes involve some long-term gene flow perhaps due to repeated cycles of allopatry and contact, without requiring an extensive allopatric phase.
Single cell RNA-sequencing of feline peripheral immune cells with V(D)J repertoire and cross species analysis of T lymphocytes
Authors: Ramarapu Raneesh , Wulcan Judit M. , Chang Haiyang , Moore Peter F. , Vernau William , Keller Stefan M. 
Published: May 2024

AbstractIntroductionThe domestic cat (Felis catus) is a valued companion animal and a model for virally induced cancers and immunodeficiencies. However, species-specific limitations such as a scarcity of immune cell markers constrain our ability to resolve immune cell subsets at sufficient detail. The goal of this study was to characterize circulating feline T cells and other leukocytes based on their transcriptomic landscape and T-cell receptor repertoire using single cell RNA-sequencing.MethodsPeripheral blood from 4 healthy cats was enriched for T cells by flow cytometry cell sorting using a mouse anti-feline CD5 monoclonal antibody. Libraries for whole transcriptome, alpha/beta T cell receptor transcripts and gamma/delta T cell receptor transcripts were constructed using the 10x Genomics Chromium Next GEM Single Cell 5’ reagent kit and the Chromium Single Cell V(D)J Enrichment Kit with custom reverse primers for the feline orthologs.ResultsUnsupervised clustering of whole transcriptome data revealed 7 major cell populations - T cells, neutrophils, monocytic cells, B cells, plasmacytoid dendritic cells, mast cells and platelets. Sub cluster analysis of T cells resolved naive (CD4+ and CD8+), CD4+ effector T cells, CD8+ cytotoxic T cells and gamma/delta T cells. Cross species analysis revealed a high conservation of T cell subsets along an effector gradient with equitable representation of veterinary species (horse, dog, pig) and humans with the cat. Our V(D)J repertoire analysis demonstrated a skewed T-cell receptor alpha gene usage and a restricted T-cell receptor gamma junctional length in CD8+ cytotoxic T cells compared to other alpha/beta T cell subsets. Among myeloid cells, we resolved three clusters of classical monocytes with polarization into pro- and anti-inflammatory phenotypes in addition to a cluster of conventional dendritic cells. Lastly, our neutrophil sub clustering revealed a larger mature neutrophil cluster and a smaller exhausted/activated cluster.DiscussionOur study is the first to characterize subsets of circulating T cells utilizing an integrative approach of single cell RNA-sequencing, V(D)J repertoire analysis and cross species analysis. In addition, we characterize the transcriptome of several myeloid cell subsets and demonstrate immune cell relatedness across different species.
SCIITensor: A tensor decomposition based algorithm to construct actionable TME modules with spatially resolved intercellular communications
Authors: Huang Huaqiang , Liu Chuandong , Liu Xin , Tian Jingyi , Xi Feng , Li Mei , Li Guibo , Chen Ao , Xu Xun , Liao Sha , Zhang Jiajun , Liu Xing 
Published: May 2024

AbstractAdvanced spatial transcriptomics (ST) technology has paved the way for elucidating the spatial architecture of the tumor microenvironment (TME) from multiple perspectives. However, available tools only focus on the static molecular and cellular composition of the TME when analyzing the high-throughput ST data, neglecting to uncover the in-depth spatial co-variation of intercellular communications arising from heterogeneous spatial TMEs. Here, we introduce SCIITensor, which decomposes TME modules from the perspective of spatially resolved intercellular communication by spatially quantifying the cellular and molecular interaction intensities between proximal cells within each domain. It then constructs a three-dimensional matrix, formulating the task as a matrix decomposition problem, and identifies biologically relevant spatial interactions and TME patterns using Non-Negative Tucker Decomposition (NTD). We evaluated the performance of SCIITensor on liver cancer datasets obtained from multiple ST platforms. At the research setting of a single-sample investigation, SCIITensor precisely identified a functional TME module indicating a tumor boundary structure specific domain with co-variant interaction contexts, which were involved in construction of immunosuppressive TME. Moreover, we also proved that SCIITensor was able to construct TME meta-modules across multiple samples and to further identify an immune-infiltration associated and sample-common meta-module. We demonstrate that SCIITensor is applicable for dissecting TME modules from a new perspective by constructing spatial interaction contexts using ST datasets of individual and multiple samples, providing new insights into tumor research and potential therapeutic targets.
Revealing the organic food consumption intention in Afyonkarahisar: a study on the impact of health, safety, value and attributes
Authors: Baydeni̇z Erdem , Ergün Bircan , Türkoğlu Turgut , Aytekin Engin 
Published: May 2024

PurposeThis study examines the relationship between the emphasis on organic food in Afyonkarahisar's cuisine and the growing demand for healthier and sustainable options. This study aimed to understand the factors influencing the intention to consume organic foods.Design/methodology/approachThis study uses a quantitative research method. It uses scales adapted from previous research to assess the health and safety of organic food's functional, hedonic, and social values. Data were collected using the purposive sampling method, and a sample size of 410 individuals was analyzed using the PLS-SEM method. Measurement and structural models were evaluated to assess validity, reliability, and model fit.FindingsThe results indicate that implementing health and safety practices significantly and positively affects perceptions of organic food's functional, hedonic, altruistic, and social values. Additionally, consumers' attitudes toward organic food are greatly influenced by their perceptions of functional and social value, whereas hedonic and altruistic values do not have a significant positive effect.Practical implicationsThe results of this study have a beneficial impact on food industry practitioners and policymakers. Emphasizing health and safety practices in producing and promoting organic foods can improve consumer perceptions and attitudes toward organic products. Understanding the importance of practical benefits and social issues can help companies respond effectively to consumer preferences and market organic foods.Originality/valueThis study contributes significantly to the existing literature by investigating the relationship between organic food emphasis and consumer perceptions in the unique context of Afyonkarahisar, a city renowned for its gastronomy. While focusing on Afyonkarahisar provides valuable insights into the specific values that influence consumers' attitudes toward organic food, it is essential to highlight that this research extends beyond the local context to offer broader implications and significance.
Enterprise digital development and capacity utilization
Authors: Ma Hui , Chen Shenglan , Liu Xiaoling , Wang Pengcheng 
Published: May 2024

PurposeTo enrich the research on the economic consequences of enterprise digital development from the perspective of capacity utilization.Design/methodology/approachUsing a sample of listed firms from 2010 to 2020, this paper exploits text analysis of annual reports to construct a proxy for enterprise digital development.FindingsResults show that enterprise digital development not only improves their own capacity utilization but also generates a positive spillover effect on the capacity utilization of peer firms and firms in the supply chain. Next, based on the incomplete information about market demand and potential competitors when making capacity-building decisions, the mechanism tests show that improving the accuracy of market forecasts and reducing investment surges are potential channels behind the baseline results. Cross-sectional tests show the baseline result is more pronounced when industries are highly homogeneous and when firms have access to less information.Originality/valueThis paper contributes to the research related to the economic consequences of digital development. With the development of the digital economy, the real effects of enterprise digital development have also triggered extensive interest and exploration. Existing studies mainly examine the impact on physical operations, such as specialization division of labor, innovation activities, business performance or total factor productivity (Huang, Yu, & Zhang, 2019; Yuan, Xiao, Geng, & Sheng, 2021; Wang, Kuang, & Shao, 2017; Li, Liu, & Shao, 2021; Zhao, Wang, & Li, 2021). These studies measure the economic benefits from the perspective of the supply (output) side but neglect the importance of the supply system to adapt to the actual market demand. In contrast, this paper focuses on capacity utilization, aimed at estimating the net economic effect of digital development by considering the supply-demand fit scenario. Thus, our findings enrich the relevant studies on the potential consequences of digital development.
Analysis of national strategic innovation objectives using adapted Porter’s diamond model: a comparison of Romania and Türkiye
Authors: Militaru Andreea Maria Gabriela , Kurt Atil , Gumus Mehmet 
Published: May 2024

Purpose
Nowadays, nations are rapidly changing and evolving, both because of global competitiveness and technological development. The fast change of the economies and the interconnected world has brought a more globalized world than ever. The purpose of this paper is to assess Romania (RO) and Türkiye (TR) by using a customized version of Porter’s diamond model (PDM), with an emphasis on identifying the key components of their innovation systems.

Design/methodology/approach
The paper uses a recognized model to unfold its structure. Based on the PDM, this paper tackles the topic of innovation systems both of RO and TR. Applying the model, a mapping of indicators representing components of the national innovation system is made possible. Besides the traditional four determinants (dimensions) of the model, the authors adapted it and added the technology conditions. Using the five dimensions, a comparison of strategical objectives is made between RO and TR.

Findings
The results show the potential for both countries to develop and embrace the innovation capacity, while there is still room for improvement in this regard. Another point is the map of innovation system components that were used for the comparison. The implications of innovation are analyzed at a strategical level, comparing the mapping with the national strategical objectives.

Originality/value
There are many studies using this model, however a few bring into the light the impact of innovation systems at national level. Hence, a new framework is provided to evaluate innovative systems using a selection of modern indicators. This study uses an existing model in literature, Porter’s model mapping indicators, which highlight the innovation capacity.