bluuebunny/crossref_metadata_2025_split huggingface dataset:
PVT1/miR-136/Sox2/UPF1 axis regulates the malignant phenotypes of endometrial cancer stem cells
Authors: Li Qing , Kong Fanfei , Cong Rong , Ma Jian , Wang Cuicui , Ma Xiaoxin 
Published: March 2023

AbstractTumor stem cells (TSCs) are thought to contribute to the progression and maintenance of cancer. Previous studies have suggested that plasmacytoma variant translocation 1 (PVT1) has a tumor-promoting effect on endometrial cancer; however, its mechanism of action in endometrial cancer stem cells (ECSCs) is unknown. Here, we found that PVT1 was highly expressed in endometrial cancers and ECSCs, correlated with poor patient prognosis, promoted the malignant behavior and the stemness of endometrial cancer cells (ECCs) and ECSCs. In contrast, miR-136, which was lowly expressed in endometrial cancer and ECSCs, had the opposite effect, and knockdown miR-136 inhibited the anticancer effects of down-regulated PVT1. PVT1 affected miR-136 specifically binding the 3’ UTR region of Sox2 by competitively “sponging” miR-136, thus positively saving Sox2. Sox2 promoted the malignant behavior and the stemness of ECCs and ECSCs, and overexpression Sox2 inhibited the anticancer effects of up-regulated miR-136. Sox2 can act as a transcription factor to positively regulate Up-frameshift protein 1 (UPF1) expression, thereby exerting a tumor-promoting effect on endometrial cancer. In nude mice, simultaneously downregulating PVT1 and upregulating miR-136 exerted the strongest antitumor effect. We demonstrate that the PVT1/miR-136/Sox2/UPF1 axis plays an important role in the progression and maintenance of endometrial cancer. The results suggest a novel target for endometrial cancer therapies.
Emergent collective organization of bone cells in complex curvature fields
Authors: Callens Sebastien J. P. , Fan Daniel , van Hengel Ingmar A. J. , Minneboo Michelle , Díaz-Payno Pedro J. , Stevens Molly M. , Fratila-Apachitei Lidy E. , Zadpoor Amir A. 
Published: March 2023

AbstractIndividual cells and multicellular systems respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains largely unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra. Here, we show that mathematically designed substrates with controlled curvature variations induce multicellular spatiotemporal organization of preosteoblasts. We quantify curvature-induced patterning and find that cells generally prefer regions with at least one negative principal curvature. However, we also show that the developing tissue can eventually cover unfavorably curved territories, can bridge large portions of the substrates, and is often characterized by collectively aligned stress fibers. We demonstrate that this is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer a geometric perspective on cell-environment interactions that could be harnessed in tissue engineering and regenerative medicine applications.
Polynucleotide phosphorylase protects against renal tubular injury via blocking mt-dsRNA-PKR-eIF2α axis
Authors: Zhu Yujie , Zhang Mingchao , Wang Weiran , Qu Shuang , Liu Minghui , Rong Weiwei , Yang Wenwen , Liang Hongwei , Zeng Caihong , Zhu Xiaodong , Li Limin , Liu Zhihong , Zen Ke 
Published: March 2023

AbstractRenal tubular atrophy is a hallmark of chronic kidney disease. The cause of tubular atrophy, however, remains elusive. Here we report that reduction of renal tubular cell polynucleotide phosphorylase (PNPT1) causes renal tubular translation arrest and atrophy. Analysis of tubular atrophic tissues from renal dysfunction patients and male mice with ischemia-reperfusion injuries (IRI) or unilateral ureteral obstruction (UUO) treatment shows that renal tubular PNPT1 is markedly downregulated under atrophic conditions. PNPT1 reduction leads to leakage of mitochondrial double-stranded RNA (mt-dsRNA) into the cytoplasm where it activates protein kinase R (PKR), followed by phosphorylation of eukaryotic initiation factor 2α (eIF2α) and protein translational termination. Increasing renal PNPT1 expression or inhibiting PKR activity largely rescues IRI- or UUO-induced mouse renal tubular injury. Moreover, tubular-specific PNPT1-knockout mice display Fanconi syndrome-like phenotypes with impaired reabsorption and significant renal tubular injury. Our results reveal that PNPT1 protects renal tubules by blocking the mt-dsRNA-PKR-eIF2α axis.
The dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
Authors: Meier Markus , Gupta Monika , Akgül Serife , McDougall Matthew , Imhof Thomas , Nikodemus Denise , Reuten Raphael , Moya-Torres Aniel , To Vu , Ferens Fraser , Heide Fabian , Padilla-Meier Gay Pauline , Kukura Philipp , Huang Wenming , Gerisch Birgit , Mörgelin Matthias , Poole Kate , Antebi Adam , Koch Manuel , Stetefeld Jörg 
Published: March 2023

AbstractNetrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.
Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans
Authors: Ravindra Kodihalli C. , Vaidya Vishal S. , Wang Zhenyu , Federspiel Joel D. , Virgen-Slane Richard , Everley Robert A. , Grove Jane I. , Stephens Camilla , Ocana Mireia F. , Robles-Díaz Mercedes , Isabel Lucena M. , Andrade Raul J. , Atallah Edmond , Gerbes Alexander L. , Weber Sabine , Cortez-Pinto Helena , Fowell Andrew J. , Hussaini Hyder , Bjornsson Einar S. , Patel Janisha , Stirnimann Guido , Verma Sumita , Elsharkawy Ahmed M. , Griffiths William J. H. , Hyde Craig , Dear James W. , Aithal Guruprasad P. , Ramaiah Shashi K. 
Published: March 2023

AbstractDiagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94–0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65–0.78), but further technical and clinical validation of these candidate biomarkers is needed.
Cryo-EM structure of human heptameric pannexin 2 channel
Authors: Zhang Hang , Wang Shiyu , Zhang Zhenzhen , Hou Mengzhuo , Du Chunyu , Zhao Zhenye , Vogel Horst , Li Zhifang , Yan Kaige , Zhang Xiaokang , Lu Jianping , Liang Yujie , Yuan Shuguang , Wang Daping , Zhang Huawei 
Published: March 2023

AbstractPannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating.
mTORC1 upregulates B7-H3/CD276 to inhibit antitumor T cells and drive tumor immune evasion
Authors: Liu Heng-Jia , Du Heng , Khabibullin Damir , Zarei Mahsa , Wei Kevin , Freeman Gordon J. , Kwiatkowski David J. , Henske Elizabeth P. 
Published: March 2023

AbstractIdentifying the mechanisms underlying the regulation of immune checkpoint molecules and the therapeutic impact of targeting them in cancer is critical. Here we show that high expression of the immune checkpoint B7-H3 (CD276) and high mTORC1 activity correlate with immunosuppressive phenotypes and worse clinical outcomes in 11,060 TCGA human tumors. We find that mTORC1 upregulates B7-H3 expression via direct phosphorylation of the transcription factor YY2 by p70 S6 kinase. Inhibition of B7-H3 suppresses mTORC1-hyperactive tumor growth via an immune-mediated mechanism involving increased T-cell activity and IFN-γ responses coupled with increased tumor cell expression of MHC-II. CITE-seq reveals strikingly increased cytotoxic CD38+CD39+CD4+ T cells in B7-H3-deficient tumors. In pan-human cancers, a high cytotoxic CD38+CD39+CD4+ T-cell gene signature correlates with better clinical prognosis. These results show that mTORC1-hyperactivity, present in many human tumors including tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM), drives B7-H3 expression leading to suppression of cytotoxic CD4+ T cells.
Quantitative analysis of C. elegans transcripts by Nanopore direct-cDNA sequencing reveals terminal hairpins in non trans-spliced mRNAs
Authors: Bernard Florian , Dargère Delphine , Rechavi Oded , Dupuy Denis 
Published: March 2023

AbstractIn nematodes and kinetoplastids, mRNA processing involves a trans-splicing step through which a short sequence from a snRNP replaces the original 5’ end of the primary transcript. It has long been held that 70% of C. elegans mRNAs are submitted to trans-splicing. Our recent work suggested that the mechanism is more pervasive but not fully captured by mainstream transcriptome sequencing methods. Here we use Oxford Nanopore’s long-read amplification-free sequencing technology to perform a comprehensive analysis of trans-splicing in worms. We demonstrate that spliced leader (SL) sequences at the 5’ end of the mRNAs affect library preparation and generate sequencing artefacts due to their self-complementarity. Consistent with our previous observations, we find evidence of trans-splicing for most genes. However, a subset of genes appears to be only marginally trans-spliced. These mRNAs all share the capacity to generate a 5’ terminal hairpin structure mimicking the SL structure and offering a mechanistic explanation for their non conformity. Altogether, our data provide a comprehensive quantitative analysis of SL usage in C. elegans.
Coherent optical-microwave interface for manipulation of low-field electronic clock transitions in 171Yb3+:Y2SiO5
Authors: Nicolas L. , Businger M. , Sanchez Mejia T. , Tiranov A. , Chanelière T. , Lafitte-Houssat E. , Ferrier A. , Goldner P. , Afzelius M. 
Published: March 2023

AbstractThe coherent interaction of solid-state spins with both optical and microwave fields provides a platform for a range of quantum technologies, such as quantum sensing, microwave-to-optical quantum transduction and optical quantum memories. Rare-earth ions with electronic spins are interesting in this context. In this work, we use a loop-gap microwave resonator to coherently drive optical and microwave clock transitions simultaneously in a 171Yb3+:Y2SiO5 crystal, achieving a Rabi frequency of 0.56 MHz at 2.497 GHz over a 1-cm long crystal. Furthermore, we provide insights into the spin dephasing at very low fields, showing that superhyperfine-induced collapse of the Hahn echo plays an important role. Our calculations and measurements reveal that the effective magnetic moment can be manipulated in 171Yb3+:Y2SiO5, which suppresses the superhyperfine interaction at the clock transition. At a doping concentration of 2 ppm and 3.4 K, we achieve spin coherence time of 10.0 ± 0.4 ms.
Tunable nanostructured stainless-steel coating for high-selective and high-permeable separation membranes for oil/water emulsions
Authors: Yeh Yi-Jui , Chu Jinn P. , You Jhen-De , Chang Ting-Hao , Liou Jr Rong , Chiang Wei-Hung , Yiu Pakman , Hsueh Chun-Hway , Shen Yu-Lin , Tung Kuo-Lun 
Published: March 2023

AbstractThis paper demonstrates a stainless-steel (SS) nano-pyramid structure (diameter of ~20–50 nm and pore size of 156.1 nm) sputter-coated on mixed cellulose ester (MCE) membrane for the use in separation of oil/water emulsions. SS-coated MCE membrane presented a superhydrophilic, antifouling surface as well as underwater superoleophobicity. The coated membrane achieved excellent separation efficiency of >99% when applied to light oil-water emulsions with a range of viscosities and densities. The highest permeation flux measured was 1,555 L m−2 h−1 when applied to toluene-in-water emulsions. The membrane also presented outstanding recyclability, as evidenced by oil rejection rate retaining at >99% through four separation cycles. The coated membrane was also shown to work well under harsh conditions including salty water, extreme pH values (1–14), and high temperatures (60 °C). In addition, our fabrication route of SS-coated MCE employs low process temperature while being highly scalable, which is favorable for industrial-scale applications.
Biofluorescent sexual dimorphism revealed in a southern Appalachian endemic salamander, Plethodon metcalfi
Authors: Cox Jonathan L. , Fitzpatrick Benjamin M. 
Published: March 2023

AbstractBiofluorescence occurs when a living organism absorbs high energy light and reemits it at longer wavelengths. Many species within clades of vertebrates are known to fluoresce including mammals, reptiles, birds, and fish. Most, if not all, amphibians exhibit biofluorescence when exposed to either blue (440–460 nm) or ultra-violet (360–380 nm) wavelengths of light. Salamanders (Lissamphibia: Caudata) appear to consistently fluoresce in green wavelengths (520–560 nm) when excited by blue light. Biofluorescence is theorized to have many ecological functions including mate signaling, camouflage, and mimicry. Despite the discovery of their biofluorescence, its role in salamander ecology and behavior remains unresolved. In this study we present the first case of biofluorescent sexual dimorphism within Amphibia and the first documentation of the biofluorescent pattern of a salamander within the Plethodon jordani species complex. This sexually dimorphic trait was discovered in the southern Appalachian endemic species, Southern Gray-Cheeked Salamander (Plethodon metcalfi, Brimley in Proc Biol Soc Wash 25:135–140, 1912), and may extend into other species within the Plethodon jordani and Plethodon glutinosus species complexes. We propose that this sexually dimorphic trait could be related to fluorescence of ventral modified granular glands used in plethodontid chemosensory communication.
Determination of orally administered 1,8-Cineol in nasal polyp tissues from chronic rhinosinusitis patients using gas chromatography: mass spectrometry
Authors: MacKenzie Claire , Goerke Thomas , Buecking Mark , Heidemann Mathias , Leichtle Anke , Ringbeck Benedikt , Möllenkolk Friederike , Ploch Michael , Bruchhage Karl-Ludwig , Pries Ralph 
Published: March 2023

AbstractChronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disease causing considerable disease burden. The anti-inflammatory monoterpene 1,8-Cineol is a natural plant-based therapeutic agent that is well established to treat chronic and acute airway diseases. Aim of this study was to investigate whether the herbal drug 1,8-Cineol reaches the nasal tissue via the gut and the blood stream upon its oral administration. A highly sensitive gas chromatography mass spectrometry-based method with stir bar sorptive extraction (SBSE) for sample preparation has been developed and validated for the extraction, detection and quantification of 1,8-Cineol in tissue samples of nasal polyps from 30 CRSwNP patients. Data revealed a highly sensitive detection of 1,8-Cineol in nasal tissue samples after 14 days of oral administration of 1,8-Cineol prior to surgical treatment. There was no significant correlation between the measured 1,8-Cineol concentrations and bodyweight or BMI values of the analyzed patients, respectively. Our data indicate a systemic distribution of 1,8-Cineol in the human body after its oral administration. Individual differences in terms of metabolic characteristics and have to be further investigated. The study increases our understanding of the systemic effects of 1,8-Cineol upon its therapeutic application and benefit in patients with CRSwNP.
Comparison between strip sampling and laser ablation methods to infer seasonal movements from intra-tooth strontium isotopes profiles in migratory caribou
Authors: Le Corre Mael , Grimes Vaughan , Lam Rebecca , Britton Kate 
Published: March 2023

AbstractStrontium isotopes analysis is a powerful tool in the study of past animal movements, notably the sequential analysis of tooth enamel to reconstruct individual movements in a time-series. Compared to traditional solution analysis, high resolution sampling using laser-ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) has the potential to reflect fine scale mobility. However, the averaging of the 87Sr/86Sr intake during the enamel mineralization process may limit fine scale inferences. We compared solution and LA-MC-ICP-MS 87Sr/86Sr intra-tooth profiles from the second and third molars of 5 caribou from the Western Arctic herd, Alaska. Profiles from both methods showed similar trends, reflecting the seasonal migratory movements, but LA-MC-ICP-MS profiles showed a less damped 87Sr/86Sr signal than solution profiles. Geographic assignments of the profile endmembers to the known summer and winter ranges were consistent between methods and with the expected timing of enamel formation but showed discrepancy at a finer scale. Variations on LA-MC-ICP-MS profiles, consistent with expected seasonal movements, suggested more than an admixture of the endmember values. However, more work in understanding enamel formation in Rangifer, and other ungulates, and how 87Sr/86Sr daily intake translates into enamel are needed to assess the real resolution that can be achieved with LA-MC-ICP-MS.
An edge communication based probabilistic caching for transient content distribution in vehicular networks
Authors: Gupta Divya , Rani Shalli , Tiwari Basant , Gadekallu Thippa Reddy 
Published: March 2023

AbstractVehicular Content Networks (VCNs) represent key empowering solution for content distribution in fully distributed manner for vehicular infotainment applications. In VCN, both on board unit (OBU) of each vehicle and road side units (RSUs) facilitate content caching to support timely content delivery for moving vehicles when requested. However, due to limited caching capacity available at both RSUs and OBUs, only selected content can be cached. Moreover, the contents being demanded in vehicular infotainment applications are transient in nature. The transient content caching in vehicular content networks with the use of edge communication for delay free services is fundamental issue and need to get addressed (Yang et al. in ICC 2022-IEEE international conference on communications. IEEE, pp 1–6, 2022). Therefore, this study focuses on edge communication in VCNs by firstly organizing a region based classification for vehicular network components including RSUs and OBUs. Secondly, a theoretical model is designed for each vehicle to decide its content fetching location (i.e. either RSU or OBU) in current region or neighboring region. Further, the caching of transient contents inside vehicular network components (such as RSU, OBU) is based on content caching probability. Finally, the proposed scheme is evaluated under different network condition in Icarus simulator for various performance parameters. The simulation results proved outstanding performance of the proposed approach over various state of art caching strategies.
Feature augmentation based on information fusion rectification for few-shot image classification
Authors: Wang Hang , Tian Shengzhao , Fu Yan , Zhou Junlin , Liu Jingfa , Chen Duanbing 
Published: March 2023

AbstractIn the issue of few-shot image classification, due to lack of sufficient data, directly training the model will lead to overfitting. In order to alleviate this problem, more and more methods focus on non-parametric data augmentation, which uses the information of known data to construct non-parametric normal distribution to expand samples in the support set. However, there are some differences between base class data and new ones, and the distribution of different samples belonging to same class is also different. The sample features generated by the current methods may have some deviations. A new few-shot image classification algorithm is proposed on the basis of information fusion rectification (IFR), which adequately uses the relationship between the data (including the relationship between base class data and new ones, and the relationship between support set and query set in the new class data), to rectify the distribution of support set in the new class data. In the proposed algorithm, feature of support set is expanded through sampling from the rectified normal distribution, so as to augment the data. Compared with other image augmentation algorithms, the experimental results on three few-shot datasets show that the accuracy of the proposed IFR algorithm is improved by 1.84–4.66% on 5-way 1-shot task and 0.99–1.43% on 5-way 5-shot task.