bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell analysis reveals distinct immune characteristics of hepatocellular carcinoma in HBV-positive versus HBV-negative cases
Authors: Liu Ke , Chen Erbao , Liang Jiaming , Li Yanyan , Cheng Binghua , Shi Wenli , Zhou Zeyu , Zhou Wenjie , Tian Hui , Yang Dongye , Shao Ximing , Li Hongchang 
Published: December 2024

AbstractInfection with the Hepatitis B virus (HBV) is a key risk factor for Hepatocellular carcinoma (HCC) development and progression. It is widely recognized that immunopathological mechanisms are pivotal in developing HBV-related HCC. Nevertheless, the specific mechanisms by which HBV-induced modifications within the tumor microenvironment (TME) contribute to HCC pathogenesis are still not well understood. Here, we utilized single-cell RNA sequencing to analyze and compare the immune landscapes between HBV-positive and HBV-negative HCC. We discovered that HBV infection significantly modifies the immune cell makeup and state, and leads to the suppression and exhaustion of T cells within the TME. Specifically, an increase in SLC4A10+ CD8+ T cells and IFITM3+ macrophages was observed, along with the upregulation of the gene SLC35F1 in various immune cell subtypes. These findings offer valuable insights into the alteration of the immunological microenvironment in HCC associated with HBV infection, suggesting possible targets for immunotherapeutic intervention.
The Basal Ciliary but not Cytosol PKA Specifically Regulates HH Pathway Downstream of Smoothened
Authors: Zhang Hongyu , Huang Zhuoya , Chen Shujing , Chen Guangxin , Ben Jin , Ingham Philip , Zhao Zhonghua 
Published: December 2024

AbstractEffectors of the vertebrate Hedgehog (HH) signaling pathway are organized through primary cilia (PC) that grow and retract in lockstep with the cell cycle in response to extracellular signals. Protein kinase A (PKA), a kinase with ubiquitous distribution in most cells, functions as a specific negative regulator of the HH pathway. Its functional specificity in the HH pathway has been suggested to be controlled by cAMP in the PC. However, the regulation of PKA and its functions in PC is still poorly elucidated, partially due to the lack of observation of PKA localization in PC and inconsistency in the fluctuation of ciliary cAMP with HH pathway activity. Herein, we have developed an effective biosensor for monitoring real-time PKA activity in the PC of both cultured cells and zebrafish embryos, using a ciliary specific localized FRET-based A-kinase activity probe (Nphp3N-AKAR2-CR). Although the PKA catalytic subunit (PKA-C) was not observed in PC, ciliary PKA basal activity in cells was detected by Nphp3N-AKAR2-CR. Notably, its activity was modestly increased both by inhibition and activation of the HH pathway at the level of Smoothened (Smo). In addition, we have found that only ciliary-targeted PKA and not cytosolic PKA, can specifically modulate the HH pathway, even when the integrity of the PC is disrupted. Our results suggest that a basal level of PKA activity in the PC maintains the HH pathway in the OFF state and that PKA mediated inhibition is countered by changes in GLI concentration in the PC.
CORNICHON HOMOLOG 5-dependent ER export of membrane cargoes in phosphate-starvedArabidopsisroot as revealed by membrane proteomic analysis
Authors: Liu Tzu-Yin , Tsai Ming-Hsuan , Wang Jhih-Yi , Lung Hui-Fang , Chow Hong-Xuan , Chiu Chang-Yi , Lu Chiao-An 
Published: December 2024

AbstractDeveloping plants with tolerance to low phosphate (Pi) is of interest to reducing the reliance on fertilizers and thus achieving agricultural sustainability. One strategy is to enhance the endoplasmic reticulum (ER) export of cargoes associated with Pi starvation and their trafficking to final destinations. However, the mechanisms underlying this process are underexplored. We recently discovered that theArabidopsis thaliana CORNICHON HOMOLOG 5(AtCNIH5) encodes a Pi deficiency-induced ER cargo receptor regulating Pi homeostasis. To find potential membrane cargoes ofAtCNIH5, we applied the UV-cleavable 4-hexylphenylazosulfonate (Azo)-solubilized microsomal protein extraction for iTRAQ-based proteomic analysis. We identified 4,317 proteins in Pi-limitedArabidopsisroots, with 372 upregulated and 106 downregulated incnih5. Besides PHOSPHATE TRANSPORTER 1 proteins (PHT1s), downregulation of enzymes catalyzing the biosynthesis of very long-chain fatty acids and their derivative extracellular aliphatic compounds and nucleotide sugar for cell walls is over-represented. Using the yeast split-ubiquitin and thein-plantatripartite split-GFP assays, we verified the interaction ofAtCNIH5 with the downregulated transporters incnih5, includingAtPHT1s,AtOCT1,AtURGT6,AtDTX21, andAtDTX35. Furthermore,AtCNIH5 increases in the root of the Pi overaccumulatorpho2, and its C-terminal acidic residue is not required for the interaction withAtPHT1;1, implying thatAtCNIH5 employs a distinct selection mechanism forAtPHT1;1. Importantly, increasingin-situ AtCNIH5 expression/activity boosts plant growth under Pi repletion and limitation. We proposeAtCNIH5 as a low Pi-responsive hub that controls the ER export of specific membrane cargoes, thus providing a potential engineering strategy to improve plant fitness under suboptimal Pi supply.
Transcriptional Dynamics Uncover the Role of BNIP3 in Mitophagy during Muscle Remodeling inDrosophila
Authors: Taoka Hiroki , Murakawa Tadayoshi , Kohei Kawaguchi , Koizumi Michiko , Kaminishi Tatsuya , Sakamaki Yuriko , Tanaka Kaori , Harada Akihito , Inoue Keiichi , Kanki Tomotake , Ohkawa Yasuyuki , Fujita Naonobu 
Published: December 2024

AbstractDifferentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due to the lack of a genetically trackable system. Previously, we reported that a subset of larval muscle cells is remodeled into adult abdominal muscle through an autophagy-dependent mechanism inDrosophila. To unveil the underlying mechanisms of this remodeling, we performed a comparative time-course RNA-seq analysis of isolated muscle cells with or without autophagy. It revealed both transcriptional dynamics independent of autophagy and highlighted the significance of BNIP3-mediated mitophagy in muscle remodeling. Mechanistically, we found that BNIP3 recruits autophagic machinery to mitochondria through its LC3-interacting (LIR) motif and minimal essential region (MER), which interact with Atg8a and Atg18a, respectively. Loss of BNIP3 leads to a substantial accumulation of larval mitochondria, ultimately impairing muscle remodeling. In summary, this study demonstrates that BNIP3-dependent mitophagy is critical for orchestrating the dynamic process of muscle remodeling.
Inhibition of constitutive activity of the atypical chemokine receptor ACKR3 by the small-molecule inverse agonist VUF16840
Authors: Bosma Reggie , Nesheva Desislava , Rijnsburger Merel , Riemens Rick , Adamska Justyna M. , Meyrath Max , Mobach Simon , Buzink C. Maurice , de Esch Iwan J. P. , Szpakowska Martyna , Wijtmans Maikel , Chevigne Andy , Vischer Henry F. , Leurs Rob 
Published: December 2024

AbstractThe atypical chemokine receptor 3 (ACKR3) has emerged as a promising drug target for the treatment of cancer, cardiovascular, and autoimmune diseases. In this study, we present the pharmacological characterization of VUF16840, the first small-molecule inverse agonist of ACKR3. VUF16840 effectively displaces CXCL12 binding to ACKR3 and inhibits chemokine-induced β-arrestin2 recruitment in a concentration-dependent manner. Furthermore, VUF16840 stabilizes the inactive conformation of ACKR3, as demonstrated by its ability to suppress constitutive β-arrestin2 recruitment. This inverse agonism alters ACKR3 constitutive trafficking, leading to receptor enrichment at the plasma membrane and inhibition of intracellular CXCL12 uptake. Importantly, VUF16840 exhibits high selectivity for ACKR3 over a broad panel of human chemokine receptors.These findings establish VUF16840 as a potent and selective ACKR3 inverse agonist capable of modulating constitutive and chemokine-induced signaling and internalization events. As such, VUF16840 represents a valuable pharmacological tool for exploring the molecular and translational roles of ACKR3 in both physiological and pathological contexts.
Investigating the role of sensorimotor spatial dependencies in shaping conscious access to virtual 3D objects
Authors: Motyka Paweł , Schwartzman David J. , Seth Anil K. , Suzuki Keisuke 
Published: December 2024

AbstractAccording to sensorimotor accounts of perceptual experience, the subjective veridicality of an object (the sense of its ‘presence’) builds up gradually as one learns how changes in sensory inputs depend on bodily movements. To investigate how sensorimotor interactions shape visual experience, we designed a virtual-reality-based study that allowed us to manipulate the complexity of spatial dependencies governing interactions with unfamiliar 3D objects. Participants had to learn to manually control fully visible objects that could move in congruent, opposite, novel (orthogonal), or random directions in response to their movements. The sensorimotor control tasks occurred alternately with a continuous flash suppression (CFS) task evaluating the access of stationary objects to visual awareness, operationalised as the time taken for a 3D object to break the interocular suppression. We hypothesised that objects whose motion was experienced as depending on actions in a lawful, and thus encodable, manner (i.e., according to a congruent, opposite, or novel – but not random – dependency) would overcome suppression faster than objects moving randomly in response to actions (for which there is no world-related statistical structure to learn). However, while performance in the sensorimotor tasks consistently decreased along with the difficulty of the conditions (i.e., congruent > opposite > novel > random), the pre-registered analysis yielded no significant differences in breakthrough times of objects manipulated under different coupling rules. An exploratory analysis assessing whether the acquisition of ‘sensorimotor mastery’ was associated with reduced breakthrough times also revealed no significant effects. Thus, our results suggest that one’s knowledge of how an object responds to action does not play a salient role in determining conscious access to visual stimuli. This extends previous evidence for a general ineffectiveness of sensorimotor spatial manipulations in interocular suppression paradigms. Notably, in all conditions, object movement remained tightly coupled (i.e., contingent) to the participant’s actions – and given such stimuli have already been shown to break suppression faster than uncoupled/pre-recorded visual inputs – it is possible that sensorimotor contingency was a sufficiently salient factor to override any influences related to how identifiable specific spatial dependencies were.HighlightsLearning sensorimotor control over objects was examined in novel VR tasks.We varied the complexity of spatial dependencies between manual and visual rotations.Controllable objects were expected to enter visual awareness faster in b-CFS.No differences in breakthrough times for differently complex spatial coupling rules.Sensorimotor contingency outweighs spatial congruence in affecting visual awareness.
The Novel Chaperone Activity of p47 Modulates Force-Mediated Retrotranslocation from the Endoplasmic Reticulum to the Cytosol
Authors: Chaudhuri Deep , Haldar Shubhasis 
Published: December 2024

AbstractProtein quality control in the endoplasmic reticulum (ER) maintains cellular proteostasis by regulating protein folding, assembly, and degradation. While protein translocation from the cytosol into the ER is well-studied, the reverse process, known as retrotranslocation, which exports proteins from the ER lumen or membrane into the cytosol, is less understood.In this study, we investigate the role of p47, a cofactor of the ATPase p97, in retrotranslocation and its chaperone-like activity on the model substrate talin using single-molecule magnetic tweezers. We find that p47 enhances the mechanical stability of talin, by increasing its folding probabilities by 8 pN, which generate a maximum work output of up to ∼199.5 zJ to facilitate the extraction of the protein from the ER lumen. These findings suggest that p47 interacts with substrates emerging from the ER, generating pulling forces that aid retrotranslocation, which uncovers a novel mechanistic role for p47 in ER-associated degradation, advancing the understanding of retrotranslocation.
A quantitative spatial atlas of transcriptomic, morphological, and electrophysiological cell type densities in the mouse brain
Authors: Verasztó Csaba , Roussel Yann , Kanari Lida , Markram Henry , Keller Daniel 
Published: December 2024

AbstractBrain cells can be classified into transcriptomic, morphological, and electrophysiological types. We derived a quantitative spatial atlas of the distributions of these classes within the mouse brain. To do so, we first generated a 3D atlas of transcriptomic cell type densities, by scaling regional estimates of densities from brain slices using cell counts and slice dimensions. Adjustments for regions with high cell density, such as the cerebellum, were made using the average Nissl intensities as a density modifier on a voxel-by-voxel basis. To connect the transcriptomic-type signatures to cellular function (morphological-electrophysiological types), we leveraged patch-sequencing datasets, which integrate mRNA counts, morphology reconstructions, and electrophysiological recordings from single cortical neurons. We aligned mRNA counts with the established classifications of transcriptomic types, classified neuron morphologies according to morphological types, and derived electrophysiological types using K-means clustering. The resulting 3D atlas and computational framework can be used to probe neuronal cell-type diversity and its functional implications, setting the stage for further explorations into the cellular basis of brain function.
Layilin Regulates Treg Motility and Suppressive Capacity in Skin
Authors: Gouirand Victoire , Clancy Sean , Macon Courtney , Valle Jose , Pauli Mariela , Troung Hong-An , Cohen Jarish , Kinet Maxime , Lowe Margaret M. , Lord Samuel J. , Skruber Kristen , Harris Hobart , Kim Esther , Neuhaus Isaac , Reif Karin , Zarrin Ali A. , Mullins Dyche R. , Rosenblum Michael D. 
Published: December 2024

AbstractRegulatory T cells (Tregs) are essential for maintaining immune tolerance in both lymphoid and non-lymphoid tissues. We discovered that layilin, a C-type lectin receptor, is predominantly expressed on Tregs in skin. Layilin was highly expressed on a subset of clonally expanded ‘effector’ Tregs in both healthy and psoriatic skin. Layilin expressing Tregs exhibited a transcriptional profile indicative of enhanced adhesion. Deletion of layilin in Tregsin vivoresulted in significantly attenuated skin inflammation. Mechanistically, layilin enhanced Treg adhesionviamodulation of LFA-1, resulting in distinct cytoskeletal alterations consistent with enhanced focal adhesion and lamellipodia formation. Taken together, we define layilin as a critical regulator of Treg suppressive capacity through modulating motility and adhesion in a non-lymphoid tissue.
Breast Cancer Remodels Lymphatics in Sentinel Lymph Nodes
Authors: Eichin Dominik , Takeda Akira , Lehotina Diana , Kauko Anni , Uenaka Maki , Leppänen Meri , Elima Kati , Lönnberg Tapio , Boström Pia , Koskivuo Ilkka , Aittokallio Tero , Hollmén Maija , Jalkanen Sirpa 
Published: December 2024

ABSTRACTCancer metastasis to sentinel lymph nodes (LNs) is often the first marker of potential disease progression. Although it is recognized that tumor-induced lymphangiogenesis facilitates metastasis into LNs in murine models, tumor-induced alterations in human lymphatic vessels remain obscure. We used single-cell RNA sequencing to profile lymphatic endothelial cell (LEC) subsets in paired metastatic and non-metastatic LNs obtained from patients with treatment-naïve breast cancer. Tumor metastasis decreases immunoregulatory LEC subsets, such as PD-L1+subcapsular sinus LECs, while inducing an increase in capillary-like CD200+HEY1+LECs. Matrix Gla protein (MGP) was the most upregulated gene in metastatic LN LECs, and its expression on LECs was TGF-β and VEGF dependent. Upregulated MGP promotes cancer cell adhesion to LN lymphatics. Thus, breast cancer cell metastasis to LNs remodels LEC subsets in human LNs and escalates MGP expression, potentially facilitating cancer cell dissemination through the lymphatic system.
Cytosolic Carboxypeptidase 5 maintains mammalian ependymal multicilia to ensure proper homeostasis and functions of the brain
Authors: Dad Rubina , Wang Yujuan , Fang Chuyu , Chen Yuncan , Zhang Yuan , Pan Xinwen , Zhang Xinyue , Swanekamp Emily , Patel Krish , Wolf Matthias T. F. , Yuchi Zhiguang , Zhu Xueliang , Wu Hui-Yuan 
Published: December 2024

AbstractEpendymal multicilia position at one-side on the cell surface and beat synchronously across tissue to propel the flow of cerebrospinal fluid. Loss of ependymal cilia often causes hydrocephalus. However, molecules contributing to their maintenance remain yet fully revealed. Cytosolic carboxypeptidase (CCP) family are erasers of polyglutamylation, a conserved posttranslational modification of ciliary-axoneme microtubules. CCPs possess a unique domain (N-domain) N-terminal to their carboxypeptidase (CP) domain with unclear function. Here, we show that a novel mutant mouse ofAgbl5, the gene encoding CCP5, with deletion of its N-terminus and partial CP domain (designatedAgbl5M1/M1), developed lethal hydrocephalus due to degeneration of ependymal multicilia. Interestingly, multiciliogenesis was not impaired inAgbl5M1/M1ependyma. The initially formed multicilia beat at a normal frequency, but in intercellularly diverse directions, indicative of aberrant tissue-level coordination. Moreover, actin networks are severely disrupted and basal body patches are improperly displaced in mutant cells, suggesting impaired cell polarity. In contrast,Agbl5mutants with disruption solely in the CP domain of CCP5 (Agbl5M2/M2) do not develop hydrocephalus despite increased glutamylation levels in ependymal cilia as similarly seen inAgbl5M1/M1. This study revealed an unappreciated role of CCP5, particularly its N-domain, in ependymal multicilia stability associated with their polarization and coordination.
Demystifying resistance: factors influencing users’ reluctance to share images on social media
Authors: Mir Umar Bashir , Shardeo Vipulesh 
Published: December 2024

PurposeThe study aims to explore the factors that motivate social media (SM) users to abstain from sharing pictures on SM platforms through the lens of user resistance theory (URT).Design/methodology/approachThe study adopts a mixed-method approach and utilizes the URT as a lens to explore user attitudes towards SM engagement. Insights were derived from consultations with ten domain experts possessing diverse professional backgrounds. To prioritize the identified resistance factors, the Fuzzy-OPA multi-criteria decision-making (MCDM) technique was employed.FindingsThe study identifies 13 factors influencing users' choices to abstain from sharing images on SM platforms, categorized into 2 primary groups: personal and platform-related factors. Personal factors include privacy concerns, fear of negative judgment and anxiety over self-presentation. In contrast, platform factors include perceived risks of sharing images without consent, lack of control over the privacy settings and the lack of trust in SM platforms, contributing to users' reluctance to share pictures on SM.Research limitations/implicationsThe study utilized ten experts' opinions to classify and prioritize factors, but results may vary with more experts from diverse backgrounds. Additionally, resistance factors may differ across SM platforms like Instagram, Snapchat, Facebook, etc. The study contributes to theory by identifying and classifying personal and platform barriers to SM non-use, filling a gap in existing literature. It offers a framework for future research on technology adoption and non-use, emphasizing the role of privacy, self-presentation and identity factors in user decision-making. This classification aids in designing measurement tools for further research.Practical implicationsThe study contributes to theory by identifying and classifying personal and platform barriers to SM non-use, filling a gap in existing literature. It offers a framework for future research on technology adoption and non-use, emphasizing the role of privacy, self-presentation and identity factors in user decision-making. This classification aids in designing measurement tools for further research.Originality/valueWhile most of the research on SM platforms has examined the drivers behind their adoption, reasons for non-adoption, remain relatively underexplored. The study fills this gap by investigating why users limit sharing content on SM platforms.
Perceptions of government performance and willingness to pay tax in Africa
Authors: Koomson Theodora Aba Abekah , Bekoe Rita Amoah , Owusu Godfred Matthew Yaw 
Published: December 2024

Purpose
The purpose of this study is to examine citizens’ perceptions of government performance and its impact on their willingness to pay taxes.

Design/methodology/approach
Data from the Afrobarometer round eight surveys, with a substantial 39,624 observations across 34 African countries, was analysed using ordinary least squares.

Findings
The authors uncover compelling evidence that although Africans generally have a positive attitude towards paying taxes, their decision to pay taxes is influenced by their perceptions of the government’s performance. Specifically, they find that perceptions of how the government handles economic management, provides basic health needs and protects the rights of people with disabilities significantly influence individuals’ willingness to pay taxes. Surprisingly, the authors find that although Africans rate their governments as high performers in resolving conflicts, that demotivates them from paying taxes.

Practical implications
These findings emphasise that citizens’ tax compliance goes beyond simple willingness; they also expect governments’ performance to meet their expectations.

Originality/value
To the best of the authors’ knowledge, this study is among the first to examine individual taxpayers’ perceptions of their government’s performance and its role in enhancing tax compliance across Africa.
Integrated marketing communication as a strategic tool for geographical indication
Authors: da Silva Renata Kelly , Giraldi Janaina de Moura Engracia 
Published: December 2024

PurposeIntegrated marketing communication (IMC) is a management tool that accompanies market dynamics, business environment and technological transformations and can become a competitive differential for organizations that use it. This study’s aim is to propose that IMC can be a strategic tool in the context of geographical indication (GI).Design/methodology/approachExploratory research was conducted with a qualitative approach through an integrated unique case study, including bibliographic, documentary research, direct observation and in-depth semi-structured interviews. The case chosen was the GI of Matas de Rondônia coffee, located in the Amazonia biome, which is the first denomination in the world of the sustainable Coffea canephora species and, to date, Brazil’s only GI to include indigenous lands.FindingsIt was possible to confirm all propositions, and obtain theoretical, practical and public management contributions.Originality/valueThis research brings unpublished theoretical contributions, when presenting IMC as a strategic tool for GI, fills gaps and increases the literature in the areas of marketing, communication, food marketing and GI.