bluuebunny/crossref_metadata_2025_split huggingface dataset:
ID4-dependent secretion of VEGFA enhances the invasion capability of breast cancer cells and activates YAP/TAZ via integrin β3-VEGFR2 interaction
Authors: Benedetti Anna , Turco Chiara , Gallo Enzo , Daralioti Theodora , Sacconi Andrea , Pulito Claudio , Donzelli Sara , Tito Claudia , Dragonetti Martina , Perracchio Letizia , Blandino Giovanni , Fazi Francesco , Fontemaggi Giulia 
Published: February 2024

AbstractUnderstanding the mechanisms of breast cancer cell communication underlying cell spreading and metastasis formation is fundamental for developing new therapies. ID4 is a proto-oncogene overexpressed in the basal-like subtype of triple-negative breast cancer (TNBC), where it promotes angiogenesis, cancer stem cells, and BRACA1 misfunction. Here, we show that ID4 expression in BC cells correlates with the activation of motility pathways and promotes the production of VEGFA, which stimulates the interaction of VEGFR2 and integrin β3 in a paracrine fashion. This interaction induces the downstream focal adhesion pathway favoring migration, invasion, and stress fiber formation. Furthermore, ID4/ VEGFA/ VEGFR2/ integrin β3 signaling stimulates the nuclear translocation and activation of the Hippo pathway member’s YAP and TAZ, two critical executors for cancer initiation and progression. Our study provides new insights into the oncogenic roles of ID4 in tumor cell migration and YAP/TAZ pathway activation, suggesting VEGFA/ VEGFR2/ integrin β3 axis as a potential target for BC treatment.
Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy
Authors: Zhang Zhiqi , Xu Xiaoxuan , Du Jiawei , Chen Xin , Xue Yonger , Zhang Jianqiong , Yang Xue , Chen Xiaoyuan , Xie Jinbing , Ju Shenghong 
Published: February 2024

AbstractImmunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.
Predicting the risk and speed of drug resistance emerging in soil-transmitted helminths during preventive chemotherapy
Authors: Coffeng Luc E. , Stolk Wilma A. , de Vlas Sake J. 
Published: February 2024

AbstractControl of soil-transmitted helminths relies heavily on regular large-scale deworming of high-risk groups (e.g., children) with benzimidazole derivatives. Although drug resistance has not yet been documented in human soil-transmitted helminths, regular deworming of cattle and sheep has led to widespread benzimidazole resistance in veterinary helminths. Here we predict the population dynamics of human soil-transmitted helminth infections and drug resistance during 20 years of regular preventive chemotherapy, using an individual-based model. With the current preventive chemotherapy strategy of mainly targeting children in schools, drug resistance may evolve in soil-transmitted helminths within a decade. More intense preventive chemotherapy strategies increase the prospects of soil-transmitted helminths elimination, but also increase the speed at which drug efficacy declines, especially when implementing community-based preventive chemotherapy (population-wide deworming). If during the last decade, preventive chemotherapy against soil-transmitted helminths has led to resistance, we may not have detected it as drug efficacy has not been structurally monitored, or incorrectly so. These findings highlight the need to develop and implement strategies to monitor and mitigate the evolution of benzimidazole resistance.
Ultra-stable and highly reactive colloidal gold nanoparticle catalysts protected using multi-dentate metal oxide nanoclusters
Authors: Xia Kang , Yatabe Takafumi , Yonesato Kentaro , Kikkawa Soichi , Yamazoe Seiji , Nakata Ayako , Ishikawa Ryo , Shibata Naoya , Ikuhara Yuichi , Yamaguchi Kazuya , Suzuki Kosuke 
Published: February 2024

AbstractOwing to their remarkable properties, gold nanoparticles are applied in diverse fields, including catalysis, electronics, energy conversion and sensors. However, for catalytic applications of colloidal gold nanoparticles, the trade-off between their reactivity and stability is a significant concern. Here we report a universal approach for preparing stable and reactive colloidal small (~3 nm) gold nanoparticles by using multi-dentate polyoxometalates as protecting agents in non-polar solvents. These nanoparticles exhibit exceptional stability even under conditions of high concentration, long-term storage, heating and addition of bases. Moreover, they display excellent catalytic performance in various oxidation reactions of organic substrates using molecular oxygen as the sole oxidant. Our findings highlight the ability of inorganic multi-dentate ligands with structural stability and robust steric and electronic effects to confer stability and reactivity upon gold nanoparticles. This approach can be extended to prepare metal nanoparticles other than gold, enabling the design of novel nanomaterials with promising applications.
Synchrotron intensity gradient revealing magnetic fields in galaxy clusters
Authors: Hu Yue , Stuardi C. , Lazarian A. , Brunetti G. , Bonafede A. , Ho Ka Wai 
Published: February 2024

AbstractMagnetic fields and their dynamical interplay with matter in galaxy clusters contribute to the physical properties and evolution of the intracluster medium. However, the current understanding of the origin and properties of cluster magnetic fields is still limited by observational challenges. In this article, we map the magnetic fields at hundreds-kpc scales of five clusters RXC J1314.4-2515, Abell 2345, Abell 3376, MCXC J0352.4-7401, and El Gordo using the synchrotron intensity gradient technique in conjunction with high-resolution radio observations from the Jansky Very Large Array (JVLA) and the Karoo Array Telescope (MeerKAT). We demonstrate that the magnetic field orientation of radio relics derived from synchrotron intensity gradient is in agreement with that obtained with synchrotron polarization. Most importantly, the synchrotron intensity gradient is not limited by Faraday depolarization in the cluster central regions and allows us to map magnetic fields in the radio halos of RXC J1314.4-2515 and El Gordo. We find that magnetic fields in radio halos exhibit a preferential direction along the major merger axis and show turbulent structures at higher angular resolution. The results are consistent with expectations from numerical simulations, which predict turbulent magnetic fields in cluster mergers that are stirred and amplified by matter motions.
Skin muscle is the initial site of viral replication for arboviral bunyavirus infection
Authors: Schneider Christine A. , Leung Jacqueline M. , Valenzuela-Leon Paola Carolina , Golviznina Natalya A. , Toso Erik A. , Bosnakovski Darko , Kyba Michael , Calvo Eric , Peterson Karin E. 
Published: February 2024

AbstractThe first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.
Host association and intracellularity evolved multiple times independently in the Rickettsiales
Authors: Castelli Michele , Nardi Tiago , Gammuto Leandro , Bellinzona Greta , Sabaneyeva Elena , Potekhin Alexey , Serra Valentina , Petroni Giulio , Sassera Davide 
Published: February 2024

AbstractThe order Rickettsiales (Alphaproteobacteria) encompasses multiple diverse lineages of host-associated bacteria, including pathogens, reproductive manipulators, and mutualists. Here, in order to understand how intracellularity and host association originated in this order, and whether they are ancestral or convergently evolved characteristics, we built a large and phylogenetically-balanced dataset that includes de novo sequenced genomes and a selection of published genomic and metagenomic assemblies. We perform detailed functional reconstructions that clearly indicates “late” and parallel evolution of obligate host-association in different Rickettsiales lineages. According to the depicted scenario, multiple independent horizontal acquisitions of transporters led to the progressive loss of biosynthesis of nucleotides, amino acids and other metabolites, producing distinct conditions of host-dependence. Each clade experienced a different pattern of evolution of the ancestral arsenal of interaction apparatuses, including development of specialised effectors involved in the lineage-specific mechanisms of host cell adhesion and/or invasion.
The synthetic NLR RGA5HMA5 requires multiple interfaces within and outside the integrated domain for effector recognition
Authors: Zhang Xin , Liu Yang , Yuan Guixin , Wang Shiwei , Wang Dongli , Zhu Tongtong , Wu Xuefeng , Ma Mengqi , Guo Liwei , Guo Hailong , Bhadauria Vijai , Liu Junfeng , Peng You-Liang 
Published: February 2024

AbstractSome plant sensor nucleotide-binding leucine-rich repeat (NLR) receptors detect pathogen effectors through their integrated domains (IDs). Rice RGA5 sensor NLR recognizes its corresponding effectors AVR-Pia and AVR1-CO39 from the blast fungus Magnaporthe oryzae through direct binding to its heavy metal-associated (HMA) ID to trigger the RGA4 helper NLR-dependent resistance in rice. Here, we report a mutant of RGA5 named RGA5HMA5 that confers complete resistance in transgenic rice plants to the M. oryzae strains expressing the noncorresponding effector AVR-PikD. RGA5HMA5 carries three engineered interfaces, two of which lie in the HMA ID and the other in the C-terminal Lys-rich stretch tailing the ID. However, RGA5 variants having one or two of the three interfaces, including replacing all the Lys residues with Glu residues in the Lys-rich stretch, failed to activate RGA4-dependent cell death of rice protoplasts. Altogether, this work demonstrates that sensor NLRs require a concerted action of multiple surfaces within and outside the IDs to both recognize effectors and activate helper NLR-mediated resistance, and has implications in structure-guided designing of sensor NLRs.
Monitoring ocean currents during the passage of Typhoon Muifa using optical-fiber distributed acoustic sensing
Authors: Lin Jianmin , Fang Sunke , He Runjing , Tang Qunshu , Qu Fengzhong , Wang Baoshan , Xu Wen 
Published: February 2024

AbstractIn situ observations under typhoon conditions are sparse and limited. Distributed acoustic sensing (DAS) is an emerging technology that uses submarine optical-fiber (OF) cables to monitor the sea state. Here, we present DAS-based ocean current observations when a super typhoon passed overhead. The microseismic noise induced by ocean surface gravity waves (OSGWs) during Typhoon Muifa (2022) is observed in the ~0.08–0.38 Hz frequency band, with high-frequency (>0.3 Hz) component being tidally modulated. The OSGW propagation along the entire cable is successfully revealed via frequency–wavenumber analysis. Further, a method based on the current-induced Doppler shifts of DAS-recorded OSGW dispersions is proposed to calculate both speeds and directions of horizontal ocean currents. The measured current is consistent with the tidally induced sea-level fluctuations and sea-surface winds observed at a nearby ocean buoy. These observations demonstrate the feasibility of monitoring the ocean current under typhoon conditions using DAS-instrumented cables.
Unraveling the genetic architecture of congenital vertebral malformation with reference to the developing spine
Authors: Zhao Sen , Zhao Hengqiang , Zhao Lina , Cheng Xi , Zheng Zhifa , Wu Mengfan , Wen Wen , Wang Shengru , Zhou Zixiang , Xie Haibo , Ruan Dengfeng , Li Qing , Liu Xinquan , Ou Chengzhu , Li Guozhuang , Zhao Zhengye , Chen Guilin , Niu Yuchen , Yin Xiangjie , Hu Yuhong , Zhang Xiaochen ,   Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study, Liu Sen , Yan Zihui , Li Xiaoxin , Liu Bowen , Huang Yingzhao , Gao Guangxi , Liu Qing , Yang Jianle , Yang Xinyu , Maheshati Aoran , Cai Jihao , Zhu Yuanpeng , Wang Jie , Yang Yang , Li Ziquan , Lin Guanfeng , Ye Xiaohan , Liu Pengfei , Qiu Guixing , Liu Wanlu , Zhao Chengtian , Wu Zhihong , Zhang Jianguo , Wu Nan 
Published: February 2024

AbstractCongenital vertebral malformation, affecting 0.13–0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.
Synchrony of Bird Migration with Global Dispersal of Avian Influenza Reveals Exposed Bird Orders
Authors: Yang Qiqi , Wang Ben , Lemey Phillipe , Dong Lu , Mu Tong , Wiebe R. Alex , Guo Fengyi , Trovão Nídia Sequeira , Park Sang Woo , Lewis Nicola , Tsui Joseph L.-H. , Bajaj Sumali , Cheng Yachang , Yang Luojun , Haba Yuki , Li Bingying , Zhang Guogang , Pybus Oliver G. , Tian Huaiyu , Grenfell Bryan 
Published: February 2024

AbstractHighly pathogenic avian influenza virus (HPAIV) A H5, particularly clade 2.3.4.4, has caused worldwide outbreaks in domestic poultry, occasional spillover to humans, and increasing deaths of diverse species of wild birds since 2014. Wild bird migration is currently acknowledged as an important ecological process contributing to the global dispersal of HPAIV H5. However, this mechanism has not been quantified using bird movement data from different species, and the timing and location of exposure of different species is unclear. We sought to explore these questions through phylodynamic analyses based on empirical data of bird movement tracking and virus genome sequences of clade 2.3.4.4 and 2.3.2.1. First, we demonstrate that seasonal bird migration can explain salient features of the global dispersal of clade 2.3.4.4. Second, we detect synchrony between the seasonality of bird annual cycle phases and virus lineage movements. We reveal the differing exposed bird orders at geographical origins and destinations of HPAIV H5 clade 2.3.4.4 lineage movements, including relatively under-discussed orders. Our study provides a phylodynamic framework that links the bird movement ecology and genomic epidemiology of avian influenza; it highlights the importance of integrating bird behavior and life history in avian influenza studies.
Influence of microgravity on spontaneous calcium activity of primary hippocampal neurons grown in microfluidic chips
Authors: Lecoq Pierre-Ewen , Dupuis Chloé , Mousset Xavier , Benoit-Gonnin Xavier , Peyrin Jean-Michel , Aider Jean-Luc 
Published: February 2024

AbstractThe influence of variations of gravity, either hypergravity or microgravity, on the brain of astronauts is a major concern for long journeys in space, to the Moon or to Mars, or simply long-duration missions on the ISS (International Space Station). Monitoring brain activity, before and after ISS missions already demonstrated important and long term effects on the brains of astronauts. In this study, we focus on the influence of gravity variations at the cellular level on primary hippocampal neurons. A dedicated setup has been designed and built to perform live calcium imaging during parabolic flights. During a CNES (Centre National d’Etudes Spatiales) parabolic flight campaign, we were able to observe and monitor the calcium activity of 2D networks of neurons inside microfluidic devices during gravity changes over different parabolas. Our preliminary results clearly indicate a modification of the calcium activity associated to variations of gravity.
Dopamine transients follow a striatal gradient of reward time horizons
Authors: Mohebi Ali , Wei Wei , Pelattini Lilian , Kim Kyoungjun , Berke Joshua D. 
Published: February 2024

AbstractAnimals make predictions to guide their behavior and update those predictions through experience. Transient increases in dopamine (DA) are thought to be critical signals for updating predictions. However, it is unclear how this mechanism handles a wide range of behavioral timescales—from seconds or less (for example, if singing a song) to potentially hours or more (for example, if hunting for food). Here we report that DA transients in distinct rat striatal subregions convey prediction errors based on distinct time horizons. DA dynamics systematically accelerated from ventral to dorsomedial to dorsolateral striatum, in the tempo of spontaneous fluctuations, the temporal integration of prior rewards and the discounting of future rewards. This spectrum of timescales for evaluative computations can help achieve efficient learning and adaptive motivation for a broad range of behaviors.
A quantitative and site-specific atlas of the citrullinome reveals widespread existence of citrullination and insights into PADI4 substrates
Authors: Rebak Alexandra S. , Hendriks Ivo A. , Elsborg Jonas D. , Buch-Larsen Sara C. , Nielsen Claus H. , Terslev Lene , Kirsch Rebecca , Damgaard Dres , Doncheva Nadezhda T. , Lennartsson Caroline , Rykær Martin , Jensen Lars J. , Christophorou Maria A. , Nielsen Michael L. 
Published: February 2024

AbstractDespite the importance of citrullination in physiology and disease, global identification of citrullinated proteins, and the precise targeted sites, has remained challenging. Here we employed quantitative-mass-spectrometry-based proteomics to generate a comprehensive atlas of citrullination sites within the HL60 leukemia cell line following differentiation into neutrophil-like cells. We identified 14,056 citrullination sites within 4,008 proteins and quantified their regulation upon inhibition of the citrullinating enzyme PADI4. With this resource, we provide quantitative and site-specific information on thousands of PADI4 substrates, including signature histone marks and transcriptional regulators. Additionally, using peptide microarrays, we demonstrate the potential clinical relevance of certain identified sites, through distinct reactivities of antibodies contained in synovial fluid from anti-CCP-positive and anti-CCP-negative people with rheumatoid arthritis. Collectively, we describe the human citrullinome at a systems-wide level, provide a resource for understanding citrullination at the mechanistic level and link the identified targeted sites to rheumatoid arthritis.
Investigation of the potential effects of estrogen receptor modulators on immune checkpoint molecules
Authors: Abramenko Nikita , Vellieux Fréderic , Veselá Kateřina , Kejík Zdeněk , Hajduch Jan , Masařík Michal , Babula Petr , Hoskovec David , Pacák Karel , Martásek Pavel , Smetana Karel , Jakubek Milan 
Published: February 2024

AbstractImmune checkpoints regulate the immune system response. Recent studies suggest that flavonoids, known as phytoestrogens, may inhibit the PD-1/PD-L1 axis. We explored the potential of estrogens and 17 Selective Estrogen Receptor Modulators (SERMs) as inhibiting ligands for immune checkpoint proteins (CTLA-4, PD-L1, PD-1, and CD80). Our docking studies revealed strong binding energy values for quinestrol, quercetin, and bazedoxifene, indicating their potential to inhibit PD-1 and CTLA-4. Quercetin and bazedoxifene, known to modulate EGFR and IL-6R alongside estrogen receptors, can influence the immune checkpoint functionality. We discuss the impact of SERMs on PD-1 and CTLA-4, suggesting that these SERMs could have therapeutic effects through immune checkpoint inhibition. This study highlights the potential of SERMs as inhibitory ligands for immune checkpoint proteins, emphasizing the importance of considering PD-1 and CTLA-4 inhibition when evaluating SERMs as therapeutic agents. Our findings open new avenues for cancer immunotherapy by exploring the interaction between various SERMs and immune checkpoint pathways.
Transgenic Tg(Kcnj10-ZsGreen) fluorescent reporter mice allow visualization of intermediate cells in the stria vascularis
Authors: Strepay Dillon , Olszewski Rafal T. , Nixon Sydney , Korrapati Soumya , Adadey Samuel , Griffith Andrew J. , Su Yijun , Liu Jiamin , Vishwasrao Harshad , Gu Shoujun , Saunders Thomas , Roux Isabelle , Hoa Michael 
Published: February 2024

AbstractThe stria vascularis (SV) is a stratified epithelium in the lateral wall of the mammalian cochlea, responsible for both endolymphatic ion homeostasis and generation of the endocochlear potential (EP) critical for normal hearing. The SV has three layers consisting predominantly of basal, intermediate, and marginal cells. Intermediate and marginal cells form an intricate interdigitated network of cell projections making discrimination of the cells challenging. To enable intermediate cell visualization, we engineered by BAC transgenesis, reporter mouse lines expressing ZsGreen fluorescent protein under the control of Kcnj10 promoter and regulatory sequences. Kcnj10 encodes KCNJ10 protein (also known as Kir4.1 or Kir1.2), an ATP-sensitive inwardly-rectifying potassium channel critical to EP generation, highly expressed in SV intermediate cells. In these transgenic mice, ZsGreen fluorescence mimics Kcnj10 endogenous expression in the cochlea and was detected in the intermediate cells of the SV, in the inner phalangeal cells, Hensen’s, Deiters’ and pillar cells, in a subset of spiral ganglion neurons, and in glial cells. We show that expression of the transgene in hemizygous mice does not alter auditory function, nor EP. These transgenic Tg(Kcnj10-ZsGreen) mice allow live and fixed tissue visualization of ZsGreen-expressing intermediate cells and will facilitate future studies of stria vascularis cell function.