bluuebunny/crossref_metadata_2025_split huggingface dataset:
PINX1 loss confers susceptibility to PARP inhibition in pan-cancer cells
Authors: Huang Mei , Zhu Xiaotong , Wang Chen , He Liying , Li Lei , Wang Haopeng , Fan Gaofeng , Wang Yu 
Published: August 2024

AbstractPARP1 is crucial in DNA damage repair, chromatin remodeling, and transcriptional regulation. The principle of synthetic lethality has effectively guided the application of PARP inhibitors in treating tumors carrying BRCA1/2 mutations. Meanwhile, PARP inhibitors have exhibited efficacy in BRCA-proficient patients, further highlighting the necessity for a deeper understanding of PARP1 function and its inhibition in cancer therapy. Here, we unveil PIN2/TRF1-interacting telomerase inhibitor 1 (PINX1) as an uncharacterized PARP1-interacting protein that synergizes with PARP inhibitors upon its depletion across various cancer cell lines. Loss of PINX1 compromises DNA damage repair capacity upon etoposide treatment. The vulnerability of PINX1-deficient cells to etoposide and PARP inhibitors could be effectively restored by introducing either a full-length or a mutant form of PINX1 lacking telomerase inhibitory activity. Mechanistically, PINX1 is recruited to DNA lesions through binding to the ZnF3-BRCT domain of PARP1, facilitating the downstream recruitment of the DNA repair factor XRCC1. In the absence of DNA damage, PINX1 constitutively binds to PARP1, promoting PARP1-chromatin association and transcription of specific DNA damage repair proteins, including XRCC1, and transcriptional regulators, including GLIS3. Collectively, our findings identify PINX1 as a multifaceted partner of PARP1, crucial for safeguarding cells against genotoxic stress and emerging as a potential candidate for targeted tumor therapy.
NUP37 promotes the proliferation and invasion of glioma cells through DNMT1-mediated methylation
Authors: Lv Yongqiang , Wang Chaolian , Liu Ruoyu , Wu Shaoxian , Chen Junjun , Zheng Xiao , Jiang Tianwei , Chen Lujun 
Published: August 2024

AbstractNuclear regulation has potential in cancer therapy, with the nuclear pore complex (NPC) serving as a critical channel between the nucleus and cytoplasm, playing a role in regulating various biological processes and cancer. DNA methylation, an epigenetic modification mediated by DNA methyltransferases (DNMTs), influences gene expression and cell differentiation, and is crucial for the development and progression of tumor cells. Gliomas are the most common primary brain tumors, with glioblastoma being particularly aggressive, characterized by invasiveness, migration capability, and resistance to conventional treatments, resulting in poor prognosis. Our study revealed that the expression level of NUP37 affects the proliferation and invasion of glioma cells, and that the overexpression of DNMT1 can alleviate the adverse effects caused by NUP37 depletion. These findings suggest that NUP37 promotes the proliferation and invasion of glioma cells through its interaction with DNMT1.
Deciphering cell–cell communication at single-cell resolution for spatial transcriptomics with subgraph-based graph attention network
Authors: Yang Wenyi , Wang Pingping , Xu Shouping , Wang Tao , Luo Meng , Cai Yideng , Xu Chang , Xue Guangfu , Que Jinhao , Ding Qian , Jin Xiyun , Yang Yuexin , Pang Fenglan , Pang Boran , Lin Yi , Nie Huan , Xu Zhaochun , Ji Yong , Jiang Qinghua 
Published: August 2024

AbstractThe inference of cell–cell communication (CCC) is crucial for a better understanding of complex cellular dynamics and regulatory mechanisms in biological systems. However, accurately inferring spatial CCCs at single-cell resolution remains a significant challenge. To address this issue, we present a versatile method, called DeepTalk, to infer spatial CCC at single-cell resolution by integrating single-cell RNA sequencing (scRNA-seq) data and spatial transcriptomics (ST) data. DeepTalk utilizes graph attention network (GAT) to integrate scRNA-seq and ST data, which enables accurate cell-type identification for single-cell ST data and deconvolution for spot-based ST data. Then, DeepTalk can capture the connections among cells at multiple levels using subgraph-based GAT, and further achieve spatially resolved CCC inference at single-cell resolution. DeepTalk achieves excellent performance in discovering meaningful spatial CCCs on multiple cross-platform datasets, which demonstrates its superior ability to dissect cellular behavior within intricate biological processes.
A class I PI3K signalling network regulates primary cilia disassembly in normal physiology and disease
Authors: Conduit Sarah E. , Pearce Wayne , Bhamra Amandeep , Bilanges Benoit , Bozal-Basterra Laura , Foukas Lazaros C. , Cobbaut Mathias , Castillo Sandra D. , Danesh Mohammad Amin , Adil Mahreen , Carracedo Arkaitz , Graupera Mariona , McDonald Neil Q. , Parker Peter J. , Cutillas Pedro R. , Surinova Silvia , Vanhaesebroeck Bart 
Published: August 2024

AbstractPrimary cilia are antenna-like organelles which sense extracellular cues and act as signalling hubs. Cilia dysfunction causes a heterogeneous group of disorders known as ciliopathy syndromes affecting most organs. Cilia disassembly, the process by which cells lose their cilium, is poorly understood but frequently observed in disease and upon cell transformation. Here, we uncover a role for the PI3Kα signalling enzyme in cilia disassembly. Genetic PI3Kα-hyperactivation, as observed in PIK3CA-related overgrowth spectrum (PROS) and cancer, induced a ciliopathy-like phenotype during mouse development. Mechanistically, PI3Kα and PI3Kβ produce the PIP3 lipid at the cilia transition zone upon disassembly stimulation. PI3Kα activation initiates cilia disassembly through a kinase signalling axis via the PDK1/PKCι kinases, the CEP170 centrosomal protein and the KIF2A microtubule-depolymerising kinesin. Our data suggest diseases caused by PI3Kα-activation may be considered ‘Disorders with Ciliary Contributions’, a recently-defined subset of ciliopathies in which some, but not all, of the clinical manifestations result from cilia dysfunction.
Sae2 controls Mre11 endo- and exonuclease activities by different mechanisms
Authors: Tamai Tomoki , Reginato Giordano , Ojiri Ryusei , Morita Issei , Avrutis Alexandra , Cejka Petr , Shinohara Miki , Sugimoto Katsunori 
Published: August 2024

AbstractDNA double-strand breaks (DSBs) must be repaired to ensure cell survival and genomic integrity. In yeast, the Mre11-Rad50-Xrs2 complex (MRX) collaborates with Sae2 to initiate DSB repair. Sae2 stimulates two MRX nuclease activities, endonuclease and 3’−5’ exonuclease. However, how Sae2 controls the two nuclease activities remains enigmatic. Using a combined genetic and biochemical approach, we identified a separation-of-function rad50 mutation, rad50-C47, that causes a defect in Sae2-dependent MRX 3’−5’ exonuclease activity, but not endonuclease activity. We found that both the endo- and 3’−5’ exonuclease activities are essential to release Spo11 from DNA ends, whereas only the endonuclease activity is required for hairpin removal. We also uncovered that MRX-Sae2 endonuclease introduces a cleavage at defined distances from the Spo11-blocked end with gradually decreasing efficiency. Our findings demonstrate that Sae2 stimulates the MRX endo- and exonuclease activities via Rad50 by different mechanisms, ensuring diverse actions of MRX-Sae2 nuclease at DNA ends.
Control of lysogeny and antiphage defense by a prophage-encoded kinase-phosphatase module
Authors: Guo Yunxue , Tang Kaihao , Sit Brandon , Gu Jiayu , Chen Ran , Shao Xinqi , Lin Shituan , Huang Zixian , Nie Zhaolong , Lin Jianzhong , Liu Xiaoxiao , Wang Weiquan , Gao Xinyu , Liu Tianlang , Liu Fei , Luo Hongbo R. , Waldor Matthew K. , Wang Xiaoxue 
Published: August 2024

AbstractThe filamentous ‘Pf’ bacteriophages of Pseudomonas aeruginosa play roles in biofilm formation and virulence, but mechanisms governing Pf prophage activation in biofilms are unclear. Here, we identify a prophage regulatory module, KKP (kinase-kinase-phosphatase), that controls virion production of co-resident Pf prophages and mediates host defense against diverse lytic phages. KKP consists of Ser/Thr kinases PfkA and PfkB, and phosphatase PfpC. The kinases have multiple host targets, one of which is MvaU, a host nucleoid-binding protein and known prophage-silencing factor. Characterization of KKP deletion and overexpression strains with transcriptional, protein-level and prophage-based approaches indicates that shifts in the balance between kinase and phosphatase activities regulate phage production by controlling MvaU phosphorylation. In addition, KKP acts as a tripartite toxin-antitoxin system that provides defense against some lytic phages. A conserved lytic phage replication protein inhibits the KKP phosphatase PfpC, stimulating toxic kinase activity and blocking lytic phage production. Thus, KKP represents a phosphorylation-based mechanism for prophage regulation and antiphage defense. The conservation of KKP gene clusters in >1000 diverse temperate prophages suggests that integrated control of temperate and lytic phage infection by KKP-like regulatory modules may play a widespread role in shaping host cell physiology.
Enhanced metabolic entanglement emerges during the evolution of an interkingdom microbial community
Authors: Scarinci Giovanni , Ariens Jan-Luca , Angelidou Georgia , Schmidt Sebastian , Glatter Timo , Paczia Nicole , Sourjik Victor 
Published: August 2024

AbstractWhile different stages of mutualism can be observed in natural communities, the dynamics and mechanisms underlying the gradual erosion of independence of the initially autonomous organisms are not yet fully understood. In this study, by conducting the laboratory evolution on an engineered microbial community, we reproduce and molecularly track the stepwise progression towards enhanced partner entanglement. We observe that the evolution of the community both strengthens the existing metabolic interactions and leads to the emergence of de novo interdependence between partners for nitrogen metabolism, which is a common feature of natural symbiotic interactions. Selection for enhanced metabolic entanglement during the community evolution repeatedly occurred indirectly, via pleiotropies and trade-offs within cellular regulatory networks, and with no evidence of group selection. The indirect positive selection of metabolic dependencies between microbial community members, which results from the direct selection of other coupled traits in the same regulatory network, may therefore be a common but underappreciated driving force guiding the evolution of natural mutualistic communities.
METTL3/METTL14 maintain human nucleoli integrity by mediating SUV39H1/H2 degradation
Authors: Shan Yongli , Zhang Yanqi , Wei Yanxing , Zhang Cong , Lin Huaisong , He Jiangping , Wang Junwei , Guo Wenjing , Li Heying , Chen Qianyu , Zhou Tiancheng , Xing Qi , Liu Yancai , Chen Jiekai , Pan Guangjin 
Published: August 2024

AbstractNucleoli are fundamentally essential sites for ribosome biogenesis in cells and formed by liquid-liquid phase separation (LLPS) for a multilayer condensate structure. How the nucleoli integrity is maintained remains poorly understood. Here, we reveal that METTL3/METTL14, the typical methyltransferase complex catalyzing N6-methyladnosine (m6A) on mRNAs maintain nucleoli integrity in human embryonic stem cells (hESCs). METTL3/METTL14 deficiency impairs nucleoli and leads to the complete loss of self-renewal in hESCs. We further show that SUV39H1/H2 protein, the methyltransferases catalyzing H3K9me3 were dramatically elevated in METTL3/METTL14 deficient cells, which causes an accumulation and infiltration of H3K9me3 across the whole nucleolus and impairs the LLPS. Mechanistically, METTL3/METTL14 complex serves as an essential adapter for CRL4 E3 ubiquitin ligase targeting SUV39H1/H2 for polyubiquitination and proteasomal degradation and therefore prevents H3K9me3 accumulation in nucleoli. Together, these findings uncover a previously unknown role of METTL3/METTL14 to maintain nucleoli integrity by facilitating SUV39H1/H2 degradation in human cells.
Progress in computational understanding of ferroelectric mechanisms in HfO2
Authors: Zhu Tianyuan , Ma Liyang , Deng Shiqing , Liu Shi 
Published: August 2024

AbstractSince the first report of ferroelectricity in nanoscale HfO2-based thin films in 2011, this silicon-compatible binary oxide has quickly garnered intense interest in academia and industry, and continues to do so. Despite its deceivingly simple chemical composition, the ferroelectric physics supported by HfO2 is remarkably complex, arguably rivaling that of perovskite ferroelectrics. Computational investigations, especially those utilizing first-principles density functional theory (DFT), have significantly advanced our understanding of the nature of ferroelectricity in these thin films. In this review, we provide an in-depth discussion of the computational efforts to understand ferroelectric hafnia, comparing various metastable polar phases and examining the critical factors necessary for their stabilization. The intricate nature of HfO2 is intimately related to the complex interplay among diverse structural polymorphs, dopants and their charge-compensating oxygen vacancies, and unconventional switching mechanisms of domains and domain walls, which can sometimes yield conflicting theoretical predictions and theoretical-experimental discrepancies. We also discuss opportunities enabled by machine-learning-assisted molecular dynamics and phase-field simulations to go beyond DFT modeling, probing the dynamical properties of ferroelectric HfO2 and tackling pressing issues such as high coercive fields.
Integrating stereotypes and factual evidence in interpersonal communication
Authors: Koch Saskia B. J. , Tyborowska Anna , Niermann Hannah C. M. , Cillessen Antonius H. N. , Roelofs Karin , Bašnáková Jana , Toni Ivan , Stolk Arjen 
Published: August 2024

AbstractStereotypes can exert a powerful influence on our interactions with others, potentially leading to prejudice when factual evidence is ignored. Here, we identify neuroanatomical and developmental factors that influence the real-time integration of stereotypes and factual evidence during live social interactions. The study uses precisely quantified communicative exchanges in a longitudinal cohort of seventeen-year-olds followed since infancy, testing their ability to moderate stereotype tendencies toward children as contrary evidence accumulates. Our results indicate that the impact of stereotypes on communicative behavior is linked to individual variations in gray matter density and cortical thickness in the right anterior cingulate gyrus. In contrast, the ability to moderate stereotype tendencies is influenced by developmental exposure to social interactions during the initial years of life, beyond the effects of familial environment and later experiences. These findings pinpoint a key brain structure underlying stereotype tendencies and suggest that early-life social experiences have lasting consequences on how individuals integrate factual evidence in interpersonal communication.
Microbiome of esophageal endoscopic wash samples is associated with resident flora in the esophagus and incidence of cancer
Authors: Shijimaya Takuya , Tahara Tomomitsu , Yamazaki Jumpei , Kobayashi Sanshiro , Matsumoto Yasushi , Nakamura Naohiro , Takahashi Yu , Tomiyama Takashi , Fukui Toshiro , Shibata Tomoyuki , Naganuma Makoto 
Published: August 2024

AbstractChange in mucosal microbiome is associated with various types of cancer in digestive tract. We hypothesized that microbial communities in the esophageal endoscopic wash fluids reflects resident flora in esophageal mucosa that is associated with esophageal carcinoma (EC) risk and/or directly correlates microbiome derived from EC tumor tissue. Studying microbial communities in esophageal endoscopic wash samples would be therefore useful to predict the incidence or risk of EC. We examined microbial communities of the endoscopic wash samples from 45 primary EC and 20 respective non-EC controls using 16S rRNA V3-V4 amplicon sequencing. The result was also compared with microbial communities in matched endoscopic biopsies from EC and non-cancerous esophageal mucosa. Compared with non-EC controls, 6 discriminative bacterial genera were detected in EC patients. Among them, relative abundance ratio of Prevotella and Shuttlewarthia, as well as decrease of genus Prevotella presented good prognostic performance to discriminate EC from controls (area under curve, 0.86, 0.82, respectively). Multivariate analysis showed occurrence of EC was an independent factor associated with decrease of this bacteria. Abundance of genus Prevotella in the esophageal endoscopic wash samples was significantly correlated with the abundance of this bacteria in the matched endoscopic biopsies from non-cancerous esophageal mucosa but not in the EC tissues. Our findings suggest that microbiome composition in the esophageal endoscopic wash samples reflects resident flora in the esophagus and significantly correlates with the incidence of EC.
NLRP3 inflammasome pathway involved in the pathogenesis of metabolic associated fatty liver disease
Authors: Osman Heba Ahmed , Abuhamdah Sawsan M. A. , Hassan Mohammed H. , Hashim Abdelkader Ahmed , Ahmed Abdelazeem E. , Elsayed Sameh Salaheldin , El-Sawy Samer A. , Gaber Mostafa A. , Abdelhady Marwa 
Published: August 2024

AbstractThe prevalence of Metabolic-associated fatty liver disease (MAFLD) has been steadily increasing worldwide, paralleling the global epidemic of obesity and diabetes. It is estimated that approximately one-quarter of the global population is affected by MAFLD. Despite its high prevalence, MAFLD often goes undiagnosed due to the lack of specific symptoms in its early stages. However, as the disease progresses, it can lead to more severe liver-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. Therefore, we aimed to investigate the expression levels of the nucleotide-binding oligomerization domain, leucine-rich repeat (LRR)—containing proteins (NLR) family pyrin domain-containing protein 3 [NLRP3] inflammasome pathway components, NLRP3 and interleukin 1β (IL-1β) genes in patients with MAFLD with various degrees of steatosis and fibrosis. Participants were classified into two equal groups; MAFLD group: consisted of 120 patients with different degrees of hepatic fibrosis and steatosis based on fibro scan results. The non-MAFLD group was comprised of 107 participants. Molecular analysis of pyrin domain-containing protein 3 and IL-1β relative gene expressions was performed in the blood of all participants, using Real-time quantitative polymerase chain reaction (RT-qPCR). Patients with post-MAFLD hepatic fibrosis had significantly higher relative gene expression levels of IL-1β and NLRP3; with IL-1β > 1.1 had AUC of 0.919, sensitivity of 88.33, specificity of 96.26, PPV of 96.4, and NPV of 88 and 92.3 accuracy (p value < 0.001). NLRP3 > 1.33 had a sensitivity of 97.5, specificity of 99.07, PPV of 99.2, NPV of 97.2, and 98.3 accuracy with an AUC of 0.991 (p value < 0.001) as predictors of post-MAFLD hepatic fibrosis.. A significant increase in the mean relative gene expression levels of both IL-1β and NLRP3 found in patients with early fibrosis (F0-F1-2); 31.97 ± 11.8 and 6.76 ± 2.18, respectively; compared with patients with advanced hepatic fibrosis stages (F2-F3); 2.62 ± 3.71 and 4.27 ± 2.99 (p < 0.001 each). The present study provides novel evidence for the possible involvement of IL-1β and NLRP3 inflammasome in metabolic-associated fatty liver disease pathogenesis and could be valid markers for the early detection of post-MAFLD hepatic fibrosis.
Vertical structure of Caribbean deep-reef fishes from the altiphotic to deep-sea boundary
Authors: Jacquemont Juliette , Brandl Simon J. , McFarland Emily P. , Claudet Joachim , Baldwin Carole C. , Barrett Jenna , Tornabene Luke 
Published: August 2024

AbstractWhile recent technical breakthroughs have enabled advances in the description of reefs down to 150 m, the structure and depth zonation of deep-reef communities below 150 m remains largely unknown. Here, we present results from over 10 years of deep-reef fish surveys using human-occupied submersibles at four locations across the Caribbean Sea, constituting one of the only continuous reef-fish surveys from 10 to 480 m (1 site) and 40 to 300 m (3 sites). We identify four vertically stratified deep-reef fish communities between 40 and 300 m bordered by an altiphotic (0–10 m) and a deep-sea (300–480 m) community. We found a strong faunal break around 150 m that separates mesophotic and rariphotic zones and secondary breaks at ~ 70 to 90 m and ~ 180 to 200 m subdividing these zones into upper and lower communities. From 300 to 480 m in Roatán, we found a single fish community dominated by deep-sea families, indicating that the lower boundary of the reef-fish realm occurs at 300 m. No differences were found between communities ranging from 20 to 60 m, suggesting that fishes from the lower altiphotic and upper mesophotic form an ecological continuum. While some variability was observed across sites, the overall depth zonation and key species characterizing depth zones were consistent. Most deep-reef species observed were depth specialists restricted to a single depth zone, but many shallow-reef species extended down to mesophotic depths. Depth segregation among species of a genus was found across ten reef-fish genera and likely constitutes one of the mechanisms driving community distinctiveness and thereby fish diversity across depths.
Intraspecific priority effects in response to egg hatching delay in a pond-breeding salamander
Authors: Anderson Thomas L. , Rallo Trevor J. 
Published: August 2024

AbstractAs reproduction phenologies shift with climate change, populations can experience intraspecific priority effects, wherein early hatching cohorts experience an advantage over late-hatching cohorts, resulting in altered demography. Our study objective was to identify how variation in egg hatching phenology alters intraspecific interactions in small-mouthed salamanders, Ambystoma texanum. We addressed two research questions: (Q1) How are demographic responses altered by variation in the temporal duration of hatching between cohorts, and (Q2) How does the seasonality of hatching delays affect demographic responses? We manipulated hatching phenologies of A. texanum eggs and reared larvae in outdoor mesocosms to metamorphosis. For Q1, hatching delay exhibited non-linear relationships with survival and body size, with the greatest asynchrony in cohort additions resulting in the highest mortality and largest body sizes. For Q2, hatching delay effects were stronger (i.e., survival was lower and body sizes larger) when they occurred later in the season, potentially due to temperature differences that larvae experienced. Overall, our results demonstrate that changes in intraspecific interactions due to phenological shifts can be context-dependent, depending on the strength (i.e., temporal duration) and seasonality of such processes. Identifying context-dependencies of phenological shifts will be critical for predicting changes in organismal demographics with climatic shifts.