bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signals from the bone marrow B cell niches shape pre-leukemic fate in murine B cell acute lymphoblastic leukemia
Authors: Delahaye Marjorie C , Léonard Simon , Pelletier Jeoffrey , Destin Jérôme , Bardin Florence , Ounis Mourad , Monvoisin Céline , Prade Naïs , Gil Laurine , Dauba Audrey , Milpied Pierre , Khamlichi Ahmed Amine , Delabesse Eric , Marchand Tony , Broccardo Cyril , Aurrand-Lions Michel , Gerby Bastien , Mancini Stéphane JC 
Published: February 2025

AbstractThe bone marrow (BM) microenvironment plays a key role in supporting B cell development. In acute lymphoblastic leukemia (B-ALL), the acquisition of oncogenic driver mutations blocks B cell differentiation at specific stages. When these pre-leukemic cells acquire secondary mutations, B-ALL develops. However, the role of the BM microenvironment in pre-leukemic cell fate remains unknown. Here, using a murine model of spontaneous B-ALL development, we show that disrupted pre-BCR signaling in pre-leukemic cells modifies their fate. Blocking expression of the pre-BCR ligand Galectin-1 by the microenvironment impaired pre-leukemic cell proliferation and leukemia-initiating capacity. Consequently, B-ALL development was delayed, and B-ALL had a more mature phenotype, with cells expressing a BCR. Secondary mutations were also altered by changes to Galectin-1 expression, in its absence mutations almost exclusively affected IL-7R signaling rather than both pre-BCR and IL-7R signaling. These results show that signals from BM niches can directly influence pre-leukemic B cell fate.
Genomic epidemiology of enteropathogenicEscherichia coli(EPEC) in southwestern Nigeria
Authors: Akinlabi Olabisi C. , Dada Rotimi A. , Olayinka Ademola A. , Oginni-Falajiki Ibukunoluwa O. , Bejide Oyeniyi S. , Adewole Pelumi D. , Thomson Nicholas R. , Aboderin Aaron O. , Okeke Iruka N. 
Published: February 2025

AbstractBackgroundEnteropathogenicEscherichia coli(EPEC) are etiological agents of diarrhea. We studied the genetic diversity and virulence factors of EPEC in southwestern Nigeria, where this pathotype is rarely characterized.Methodology/ Principal findingsEPEC isolates (n=96) recovered from recent southwestern Nigeria diarrhea case-control studies were whole genome-sequenced using Illumina technology. Genomes were assembled using SPAdes and quality was evaluated using QUAST. Virulencefinder, SeroTypefinder, and Resfinder were used to identify virulence genes, serotypes, and resistance genes, while multilocus sequence typing was done by STtyping. Single nucleotide polymorphisms (SNPs) were called out of whole genome alignment using SNP-sites and a phylogenetic tree was constructed using IQtree. Thirty-nine of the 96 (40.6%) EPEC isolates were from cases of diarrhea. Nine isolates from diarrhea patients and four from healthy controls were typical EPEC, harboring bundle-forming pilus (bfp) genes whilst the rest were atypical EPEC. Fifteen isolates were EPEC-EAEC hybrids. Atypical serotypes O71:H19 (16, 16.6%), O108:H21 (6, 6.3%), O157:H39 (5, 5.2%), and O165:H9 (4, 4.2%) were most prevalent; only 8(8.3%) isolates belonged to classical EPEC serovars. The largest clade comprised ST517 isolates, of O71:H19 and O165:H9 serovars harboring multiple siderophore and serine protease autotransporter genes. An O71:H19 subclade comprised isolates <10 SNPs apart, representing a likely outbreak involving 15 children, four presenting with diarrhea.Conclusion/ SignificanceLikely outbreaks, of typical O119:H6(ST28) and atypical O127:H29(ST7798) were additionally identified. EPEC circulating in southwestern Nigeria are diverse and differ substantially from well-characterized lineages seen previously elsewhere. EPEC carriage and outbreaks could be commonplace but are largely undetected, hence, unreported, and require genomic surveillance for identification.
Discovery of first-in-class inhibitors of the TRF1-TIN2 protein-protein interaction by fragment screening
Authors: Casale Giacomo , Liu Manjuan , Le Bihan Yann-Vaï , Inian Oviya , Stammers Ellie , Caldwell John , van Montfort Rob L. M. , Collins Ian , Guettler Sebastian 
Published: February 2025

AbstractTRF1 is a subunit of the shelterin complex that binds to and protects the linear ends of chromosomes known as telomeres. Both genetic deletion and chemical inhibition of TRF1 have been shown to block the growth of lung carcinoma, glioblastoma, and renal cell carcinoma in mice without affecting mouse survival or tissue function, making TRF1 a potential therapeutic target in cancer1–3. Here, we report the discovery of a series of fragment hits that bind at the interface between the TRFH domain of TRF1 (TRF1TRFH) and a peptide of TIN2 (TIN2TBM), an interaction essential for the recruitment of TRF1 to shelterin, using X-ray crystallography (XChem) and ligand-observed NMR (LO-NMR) fragment screening. We discovered a first-in-class inhibitor of the TRF1-TIN2 interaction (compound40) that binds to TRF1TRFHwith a KDof 29 μM (95% CI: 20 – 41 μM), displaces a TIN2 probe with an IC50of 67 ± 28 μM, and expels TRF1 from purified shelterin. Aided by a novel crystal system of TRF1TRFH, we characterised fragments binding in a hotspot at the TRF1-TIN2 interface which will serve as a starting point for the structure-guided development of potent inhibitors of TRF1 protein-protein interactions to disrupt shelterin complex assembly.
Ligand Discrimination in Immune Cells: Signal Processing Insights into Immune Dysfunction in ER+ Breast Cancer
Authors: Matache Adina , Lima Joao Rodrigues , Kuznetsov Maxim , Urbaniak Konstancja , Branciamore Sergio , Rodin Andrei S. , Lee Peter P. , Rockne Russell C. 
Published: February 2025

AbstractPrior studies have shown that approximately 40% of estrogen receptor positive (ER+) breast cancer (BC) patients harbor immune signaling defects in their blood at diagnosis, and the presence of these defects predicts overall survival. Therefore, it is of interest to quantitatively characterize and measure signaling errors in immune signaling systems in these patients. Here we propose a novel approach combining communication theory and signal processing concepts to model ligand discrimination in immune cells in the peripheral blood. We use the model to measure the specificity of ligand discrimination in the presence of molecular noise by estimating the probability of error, which is the probability of making a wrong ligand identification. We apply our model to the JAK/STAT signaling pathway using high dimensional spectral flow cytometry measurements of transcription factors, including phosphorylated STATs and SMADs, in immune cells stimulated with several cytokines (IFNγ, IL-2, IL-6, IL-4, and IL-10) from 19 ER+ breast cancer patients and 32 healthy controls. In addition, we apply our model to 10 healthy donor samples treated with a clinically approved JAK1/2 inhibitor. Our results show reduced ligand identification accuracy and higher levels of molecular noise in BC patients as compared to healthy controls, which may indicate altered immune signaling and the potential for immune cell dysfunction in these patients. Moreover, the inhibition of JAK1/2 produces ligand misidentification and molecular noise rates similar to, or even greater than, those observed in breast cancer. These results suggest a means to improve the use of signaling kinase inhibitor therapies by identifying patients with favorable ligand discrimination specificity profiles in their immune cells.One Sentence SummaryWe use a communication model to measure ligand discrimination errors in immune cells and molecular noise in cytokine signaling in ER+ breast cancer patients as compared to healthy controls.
AMPK- and cGAS-Mediated Dual Sensing of Glucose and dsDNA Synergizes to Enhance Antitumor Immunity
Authors: Zhou Ruyuan , Pei Jingyan , Chen Shasha , Shen Qin , Wu Qirou , Liu Shengduo , Chen Chen , Feng Xin-Hua , Zou Jian , Liang Tingbo , Zhang Y. Jessie , Lin Sheng-Cai , Song Penghong , Zhang Chen-Song , Zhang Qian , Xu Pinglong 
Published: February 2025

ABSTRACTIntratumoral glucose availability is linked considerably to tumor growth, immune evasion, and metastasis. However, the precise molecular mechanisms by which glucose levels govern cellular and immune responses against tumors remain incompletely understood. Here, we explored the context of tumors of intersections between AMP-activated protein kinase (AMPK) and cGAS-STING signaling, a key pathway initiating antitumor immunity. We unexpectedly found that AMPK activation robustly enhances cGAS-STING signaling within cancer and immune cells, which potently impacts melanoma and colorectal cell senescence, organoid apoptosis, and the infiltration of CD4+and CD8+T lymphocytes. Using classic or newly developed AMPK agonist Aldometanib, TBK1S511E/S511Eknock-in (KI) mice, glucose metabolic modulator, as well as AMPKα1/α2 dKO melanoma, we demonstrated that dual sensing of intratumoral glucose and dsDNA integrated by the AMPK-TBK1 cascade is essential for initiating antitumor immunity and suppressing cancer progressions. Notably, novel AMPK agonists or intervening in glucose glycolysis by Lonidamine synergized effectively with STING agonists, substantially inhibiting melanoma growth. Therefore, these findings unravel a concise mechanism integrating glucose metabolism and innate DNA sensing into cancer cell fate and propose an effective therapeutic strategy to enhance antitumor immunity.HIGHLIGHTSDual and synergistic sensing of glucose and dsDNA facilitates antitumor immunity in melanoma and colorectal cancer;AMPK substitutes intratumoral cGAS-STING-IRF3 signaling through TBK1 phosphorylation at S511;Glucose deficiency induces cancer cell senescence, apoptosis, and T lymphocyte infiltration via the AMPK-TBK1 cascade;Newly developed AMPK agonists synergize with STING agonists to retrieve striking tumor suppression.
Parietal alpha frequency shapes own-body perception by modulating the temporal integration of bodily signals
Authors: D’Angelo Mariano , Lanfranco Renzo C. , Chancel Marie , Ehrsson H. Henrik 
Published: February 2025

AbstractAn influential proposal in the field of cognitive neuroscience suggests that alpha-frequency brain oscillations constrain the temporal sampling of external sensory signals, shaping the temporal binding window (TBW)—the interval during which sensory signals are integrated. However, whether alpha frequency modulates the integration of self-related sensory signals and the perception of the body as one’s own (body ownership) remains unknown. Here, we demonstrate that individual alpha frequency (IAF) from the parietal cortex predicted TBWs and perceptual sensitivities in body ownership and visuotactile simultaneity judgment tasks, with faster frequencies narrowing TBWs and increasing sensitivities, and vice versa. Modulating IAF through brain stimulation altered TBWs and sensitivities, establishing a causal relationship. Computational modeling linked IAF to uncertainty in asynchrony information within the causal inference process, providing a mechanism. These findings demonstrate that parietal alpha frequency shapes the sense of body ownership by modulating the temporal integration of bodily sensory signals.
Hybrid female sterility due to cohesin protection errors in oocytes
Authors: El Yakoubi Warif , Pan Bo , Akera Takashi 
Published: February 2025

AbstractHybrid incompatibility can lead to lethality and sterility of F1 hybrids, contributing to speciation. Here we found that female hybrids betweenMus musculus domesticusandMus spicilegusmice are sterile due to the failure of homologous chromosome separation in oocyte meiosis I, producing aneuploid eggs. This non-separation phenotype was driven by the mis- localization of the cohesin protector, SGO2, along the chromosome arms instead of its typical centromeric enrichment, resulting in cohesin over-protection. The upstream kinase, BUB1, showed a significantly higher activity in hybrid oocytes, explaining SGO2 mis-targeting along the chromosome arm. Higher BUB1 activity was not observed in mitosis, consistent with viable hybrid mice. Cohesion defects were also evident in hybrid mice from another genus,Peromyscus, wherein cohesin protection is weakened. Defective cohesion in oocytes is a leading cause of reduced fertility especially with advanced maternal age. Our work provides evidence that a major cause of human infertility may play a positive role in promoting mammalian speciation.
CRISPR-based shuttle cloning of 1,397 human genes into UAS vectors
Authors: Liu Xuelian , Xi Hanqing , Dai Miao , Li Xiaoxue , Xue Wen , Chen Guang , Yan Jialong , Xu Si , Ou Guifang , Luo Si , Tang Yonghong , Wei Ping , Wang Jiwu 
Published: February 2025

ABSTRACTThe construction of genome-wide DNA libraries from publicly available resources is essential for leveraging functional genomics to investigate complex biological systems. However, all existing high-throughput cloning methods for transferring DNA fragments between vectors require PCR amplification of the DNA fragments, rendering the construction of genome-wide DNA libraries labor-intensive and time-consuming. By introducing a concept of CRISPRshuttle cassette, we herein present a method named CRISPR-based shuttle cloning (CRISPRshuttle cloning). This method enables the high-throughput transfer of numerous DNA fragments from original plasmids with identical backbones to a different vector background without the need for PCR amplification of the DNA fragments. The procedure comprises two-step test tube reactions followed by bacterial transformation. Using CRISPRshuttle we successfully generated a library of GAL4/UAS-based UAS-ORF plasmids covering 1,397 human genes conserved inDrosophila. This library may serve as a valuable resource for gain-of-function screening in cultured cells and for the creation of a transgenic UAS-ORF library inDrosophila.
A theoretical exploration of protocols for treating prosthetic joint infections with combinations of antibiotics and bacteriophage
Authors: Levin Bruce R. , Gil-Gil Teresa , Berryhill Brandon A. , Woodworth Michael H. 
Published: February 2025

ABSTRACTWith the increase in the placement of prosthetic joints and other hardware in the body has come an increase in associated infections. These infections are particularly difficult to treat due to the underlying bacteria generating matrices which resist clearance by immune system effectors or antibiotics. These matrices, biofilms, have two primary ways of being eradicated, either by physical removal by debridement or by killing the underlying bacteria. The viruses which kill bacteria, bacteriophage, are readily capable of entering into biofilms and eradicating the bacteria therein. Therefore, bacteriophage have therapeutic potential as a supplement to antibiotics for the treatment of prosthetic joint infections. In this investigation, we generate a mathematical-computer simulation model to explore the contributions of the innate immune system with antibiotics, bacteriophage, and the joint action thereof in the control of biofilm-associated infections. Our results question the proposition that bacteriophage are an effective addition in the treatment of prosthetic joint infections.
Spatial and single-nucleus transcriptomic profile of a chimpanzee frontal pole
Authors: Alagöz Gökberk , Wong Maggie , Gräßle Tobias , Jäger Carsten , Morawski Markus , Kolleck Jakob , Francks Clyde , Wittig Roman M. , Crockford Catherine , Gunz Philipp , Fisher Simon E. 
Published: February 2025

AbstractChimpanzees, our closest living relatives, share a vast amount of our genetic code, with the majority of differences found in non-coding regions of the genome. Functional and gene regulatory differences drive phenotypic divergence, including the distinctive brain anatomy of humans compared to chimpanzees and other apes. However, little is known about species differences in gene expression, and how they relate to the evolution of neuroanatomy and cognition. This is primarily due to the limited availability of great ape brain samples and challenges in comparative spatial transcriptomic studies. Here, we present the first spatial transcriptomic data from a chimpanzee brain based onpost mortemtissue from an adult female, who was euthanised due to poor health. We focus on the frontal pole, a brain region that has undergone significant evolutionary changes in size and organisation since the last common ancestor of humans and chimpanzees, and is considered critical for cognitive evolution. We examined the gene expression profiles and cell-type composition of the frontal pole on the left hemisphere, including both neuronal and non-neuronal cell types across cortical layers and white matter. By integrating our spatial transcriptomic data with a publicly available single-nucleus transcriptomic dataset of the chimpanzee dorsolateral prefrontal cortex, we mapped the spatial distribution of 29 chimpanzee brain cell types. This study represents a first step towards characterisation of spatial gene regulatory differences between the brains of non-human great apes and humans.
Enhancing high-energy powder X-ray diffraction applications using a PILATUS4 CdTe detector
Authors: Donath Tilman , Trampari Sofia , Wagner Lucas , Jørgensen Mads R. V. , Gjørup Frederik H. , Checchia Stefano , Di Michiel Marco , Papillon Emmanuel , Vaughan Gavin 
Published: February 2025

Hybrid photon counting detectors have significantly advanced synchrotron research. In particular, the introduction of large cadmium telluride-based detectors in 2015 enabled a whole new range of high-energy X-ray measurements. This article describes the specifications of the new PILATUS4 cadmium telluride detector and presents results from prototype testing for high-energy powder X-ray diffraction studies conducted at two synchrotrons. The experiments concern time-resolved in situ solid-state reactions at MAX IV (Sweden) and fast-scanning X-ray diffraction computed tomography of a battery cell at the ESRF (France). The detector's high quantum efficiency up to 100 keV, combined with a maximum frame rate of 4000 Hz, enables fast data collection. This study demonstrates how these capabilities contribute to improved time and spatial resolution in high-energy powder X-ray diffraction studies, facilitating advancements in materials, chemical and energy research.
Is e-commerce widening or narrowing the income distribution gap among Chinese households?
Authors: Mei Yan , Lin Nuoyan , Hu Bangqi , Zhang Xihua 
Published: February 2025

PurposeAlthough many researchers have studied the benefits of the applications of e-commerce, few have examined the relationship between e-commerce and its effects on household income distribution. This study explores the effects of e-commerce development on household income distribution in different regions of China.Design/methodology/approachThis study uses a two-way fixed effect model for empirical analysis based on matched data from the E-commerce Development Index and the China Family Panel Studies database. The instrumental variables method is used for robustness testing.FindingsThe research findings indicate the following: (1) The development of e-commerce significantly reduces income inequality among Chinese households. For every 10% increase in e-commerce development, the income gap in China shrinks by 2.38%, with a reduction of 2.97 and 0.47% in urban and rural areas, respectively. (2) The reduction in income inequality due to e-commerce development is more pronounced in economically advanced regions. (3) The development of e-commerce in the eastern and western regions has a greater impact on reducing income inequality in urban than rural areas. In contrast, the opposite effect is observed in the central region.Originality/valueThis study contributes to existing research by examining the effects of e-commerce development on household income distribution. It has important theoretical and practical implications for issues such as narrowing the urban–rural gap.
Enhancing relationships through 60-sec videos: an analysis of relationship cultivation strategies on TikTok
Authors: Oh Jeyoung , Zhou Ziyuan , Kang Da-young , Ki Eyun-Jung 
Published: February 2025

PurposeTo understand how retail companies are using TikTok, a short-form video social media platform, this study investigates the use of relationship cultivation strategies and message appeals in TikTok videos posted by the top 100 retail companies. The study also examines the extent to which these strategies influence public engagement on TikTok.Design/methodology/approachA quantitative content analysis was conducted to analyze the use of relationship cultivation strategies and message appeals by the top 100 retail companies on TikTok. The study also applied negative binomial regression to assess the impact of these strategies on public engagement.FindingsThe findings show that the positivity strategy was the most frequently used relationship cultivation strategy, followed by networking and assurance. The analysis also revealed that about half of the videos employed at least one message appeal. The use of relationship cultivation strategies and message appeals had significant effects on public engagement.Originality/valueThis study is one of the first to examine the role of relationship cultivation strategies and message appeals in enhancing social media engagement for companies on TikTok.
Show a smiley face: the persuasive role of emoji on customers’ recycling experiences
Authors: Lee Seonjeong Ally , Lee Kiwon , Jung Shinyong 
Published: February 2025

Purpose
This study aims to investigate the role of emoji and the moderating effects of recycling messages in encouraging customers’ attitudes toward recycling and their recycling intentions via processing fluency.

Design/methodology/approach
Two 2 × 2 between-subject experiments are conducted to investigate the role of emojis, the moderating role of recycling messages and the mediating role of processing fluency on customers’ recycling experiences.

Findings
Study 1 identifies that customers’ attitudes toward recycling are enhanced when a positive emoji is used with a promotion-focused message, compared to a prevention-focused message. Study 2 finds that customers’ attitudes and recycling intentions are enhanced when a positive emoji is used with an upcycling message, compared to a recycling message. Both Study 1 and Study 2 identify the mediating role of processing fluency.

Practical implications
Results suggest strategically using emojis and various recycling messages to enhance customers’ recycling experience.

Originality/value
This study investigates the role of emojis as an effective recycling communication strategy.