bluuebunny/crossref_metadata_2025_split huggingface dataset:
NSUN2 stimulates tumor progression via enhancing TIAM2 mRNA stability in pancreatic cancer
Authors: Zhang Guizhen , Liu Liwen , Li Jianhao , Chen Yu , Wang Yun , Zhang Yize , Dong Zihui , Xue Wenhua , Sun Ranran , Cui Guangying 
Published: July 2023

AbstractNSUN2 is a nuclear RNA methyltransferase which catalyzes 5-methylcytosine (m5C), a posttranscriptional RNA modification. Aberrant m5C modification has been implicated in the development of multiple malignancies. However, its function in pancreatic cancer (PC) needs to be elucidated. Herein, we determined that NSUN2 was overexpressed in PC tissues and related to aggressive clinical features. Silence of NSUN2 by lentivirus weakened the capability of proliferation, migration and invasion of PC cells in vitro and inhibited the growth and metastasis of xenograft tumors in vivo. Contrarily, overexpression of NSUN2 stimulated PC growth and metastasis. Mechanistically, m5C-sequencing (m5C-seq) and RNA-sequencing (RNA-seq) were carried out to identify downstream targets of NSUN2 and results showed that loss of NSUN2 led to decreased m5C modification level concomitant with reduced TIAM2 mRNA expression. Further validation experiments proved that NSUN2 silence accelerated the decay of TIAM2 mRNA in a YBX1-dependent manner. Additionally, NSUN2 exerted its oncogenic function partially through enhancing TIAM2 transcription. More importantly, disruption of the NSUN2/TIAM2 axis repressed the malignant phenotype of PC cells through blocking epithelial-mesenchymal transition (EMT). Collectively, our study highlighted the critical function of NSUN2 in PC and provided novel mechanistic insights into NSUN2/TIAM2 axis as promising therapeutic targets against PC.
Transient receptor potential ankyrin 1 (TRPA1) mediates reactive oxygen species-induced Ca2+ entry, mitochondrial dysfunction, and caspase-3/7 activation in primary cultures of metastatic colorectal carcinoma cells
Authors: Faris Pawan , Rumolo Agnese , Pellavio Giorgia , Tanzi Matteo , Vismara Mauro , Berra-Romani Roberto , Gerbino Andrea , Corallo Salvatore , Pedrazzoli Paolo , Laforenza Umberto , Montagna Daniela , Moccia Francesco 
Published: July 2023

AbstractColorectal carcinoma (CRC) represents the fourth most common cancer worldwide and is the third most common cause of malignancy-associated mortality. Distant metastases to the liver and lungs are the main drivers of CRC-dependent death. Pro-oxidant therapies, which halt disease progression by exacerbating oxidative stress, represent an antitumour strategy that is currently exploited by chemotherapy and ionizing radiation. A more selective strategy to therapeutically exploit reactive oxygen species (ROS) signaling would consist in targeting a redox sensor that is up-regulated in metastatic cells and is tightly coupled to the stimulation of cancer cell death programs. The non-selective cation channel, Transient Receptor Potential Ankyrin 1 (TRPA1), serves as a sensor of the cellular redox state, being activated to promote extracellular Ca2+ entry by an increase in oxidative stress. Recent work demonstrated that TRPA1 channel protein is up-regulated in several cancer types and that TRPA1-mediated Ca2+ signals can either engage an antiapoptotic pro-survival signaling pathway or to promote mitochondrial Ca2+ dysfunction and apoptosis. Herein, we sought to assess for the first time the outcome of TRPA1 activation by ROS on primary cultures of metastatic colorectal carcinoma (mCRC cells). We found that TRPA1 channel protein is up-regulated and mediates enhanced hydrogen peroxide (H2O2)-induced Ca2+ entry in mCRC cells as compared to non-neoplastic control cells. The lipid peroxidation product 4-hydroxynonenal (4-HNE) is the main ROS responsible for TRPA1 activation upon mCRC cell exposure to oxidative stress. TRPA1-mediated Ca2+ entry in response to H2O2 and 4-HNE results in mitochondrial Ca2+ overload, followed by mitochondrial depolarization and caspase-3/7 activation. Therefore, targeting TRPA1 could represent an alternative strategy to eradicate metastatic CRC by enhancing its sensitivity to oxidative stress.
Quantum simulation of thermodynamics in an integrated quantum photonic processor
Authors: Somhorst F. H. B. , van der Meer R. , Correa Anguita M. , Schadow R. , Snijders H. J. , de Goede M. , Kassenberg B. , Venderbosch P. , Taballione C. , Epping J. P. , van den Vlekkert H. H. , Timmerhuis J. , Bulmer J. F. F. , Lugani J. , Walmsley I. A. , Pinkse P. W. H. , Eisert J. , Walk N. , Renema J. J. 
Published: July 2023

AbstractOne of the core questions of quantum physics is how to reconcile the unitary evolution of quantum states, which is information-preserving and time-reversible, with evolution following the second law of thermodynamics, which, in general, is neither. The resolution to this paradox is to recognize that global unitary evolution of a multi-partite quantum state causes the state of local subsystems to evolve towards maximum-entropy states. In this work, we experimentally demonstrate this effect in linear quantum optics by simultaneously showing the convergence of local quantum states to a generalized Gibbs ensemble constituting a maximum-entropy state under precisely controlled conditions, while introducing an efficient certification method to demonstrate that the state retains global purity. Our quantum states are manipulated by a programmable integrated quantum photonic processor, which simulates arbitrary non-interacting Hamiltonians, demonstrating the universality of this phenomenon. Our results show the potential of photonic devices for quantum simulations involving non-Gaussian states.
Achieving near-perfect light absorption in atomically thin transition metal dichalcogenides through band nesting
Authors: Lee Seungjun , Seo Dongjea , Park Sang Hyun , Izquierdo Nezhueytl , Lee Eng Hock , Younas Rehan , Zhou Guanyu , Palei Milan , Hoffman Anthony J. , Jang Min Seok , Hinkle Christopher L. , Koester Steven J. , Low Tony 
Published: July 2023

AbstractNear-perfect light absorbers (NPLAs), with absorbance, $${{{{{{{\mathcal{A}}}}}}}}$$
A
, of at least 99%, have a wide range of applications ranging from energy and sensing devices to stealth technologies and secure communications. Previous work on NPLAs has mainly relied upon plasmonic structures or patterned metasurfaces, which require complex nanolithography, limiting their practical applications, particularly for large-area platforms. Here, we use the exceptional band nesting effect in TMDs, combined with a Salisbury screen geometry, to demonstrate NPLAs using only two or three uniform atomic layers of transition metal dichalcogenides (TMDs). The key innovation in our design, verified using theoretical calculations, is to stack monolayer TMDs in such a way as to minimize their interlayer coupling, thus preserving their strong band nesting properties. We experimentally demonstrate two feasible routes to controlling the interlayer coupling: twisted TMD bi-layers and TMD/buffer layer/TMD tri-layer heterostructures. Using these approaches, we demonstrate room-temperature values of $${{{{{{{\mathcal{A}}}}}}}}$$
A
=95% at λ=2.8 eV with theoretically predicted values as high as 99%. Moreover, the chemical variety of TMDs allows us to design NPLAs covering the entire visible range, paving the way for efficient atomically-thin optoelectronics.
Regulation of the macrolide resistance ABC-F translation factor MsrD
Authors: Fostier Corentin R. , Ousalem Farès , Leroy Elodie C. , Ngo Saravuth , Soufari Heddy , Innis C. Axel , Hashem Yaser , Boël Grégory 
Published: July 2023

AbstractAntibiotic resistance ABC-Fs (ARE ABC-Fs) are translation factors that provide resistance against clinically important ribosome-targeting antibiotics which are proliferating among pathogens. Here, we combine genetic and structural approaches to determine the regulation of streptococcal ARE ABC-F gene msrD in response to macrolide exposure. We show that binding of cladinose-containing macrolides to the ribosome prompts insertion of the leader peptide MsrDL into a crevice of the ribosomal exit tunnel, which is conserved throughout bacteria and eukaryotes. This leads to a local rearrangement of the 23 S rRNA that prevents peptide bond formation and accommodation of release factors. The stalled ribosome obstructs the formation of a Rho-independent terminator structure that prevents msrD transcriptional attenuation. Erythromycin induction of msrD expression via MsrDL, is suppressed by ectopic expression of mrsD, but not by mutants which do not provide antibiotic resistance, showing correlation between MsrD function in antibiotic resistance and its action on this stalled complex.
ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair
Authors: Maritz Corina , Khaleghi Reihaneh , Yancoskie Michelle N. , Diethelm Sarah , Brülisauer Sonja , Ferreira Natalia Santos , Jiang Yang , Sturla Shana J. , Naegeli Hanspeter 
Published: July 2023

AbstractTo recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT.
Targeted protein degradation reveals BET bromodomains as the cellular target of Hedgehog pathway inhibitor-1
Authors: Bagka Meropi , Choi Hyeonyi , Héritier Margaux , Schwaemmle Hanna , Pasquer Quentin T. L. , Braun Simon M. G. , Scapozza Leonardo , Wu Yibo , Hoogendoorn Sascha 
Published: July 2023

AbstractTarget deconvolution of small molecule hits from phenotypic screens presents a major challenge. Many screens have been conducted to find inhibitors for the Hedgehog signaling pathway – a developmental pathway with many implications in health and disease – yielding many hits but only few identified cellular targets. We here present a strategy for target identification based on Proteolysis-Targeting Chimeras (PROTACs), combined with label-free quantitative proteomics. We develop a PROTAC based on Hedgehog Pathway Inhibitor-1 (HPI-1), a phenotypic screen hit with unknown cellular target. Using this Hedgehog Pathway PROTAC (HPP) we identify and validate BET bromodomains as the cellular targets of HPI-1. Furthermore, we find that HPP-9 is a long-acting Hedgehog pathway inhibitor through prolonged BET bromodomain degradation. Collectively, we provide a powerful PROTAC-based approach for target deconvolution, that answers the longstanding question of the cellular target of HPI-1 and yields a PROTAC that acts on the Hedgehog pathway.
Biomarkers selection and mathematical modeling in biological age estimation
Authors: Bafei Solim Essomandan Clémence , Shen Chong 
Published: July 2023

AbstractBiological age (BA) is important for clinical monitoring and preventing aging-related disorders and disabilities. Clinical and/or cellular biomarkers are measured and integrated in years using mathematical models to display an individual’s BA. To date, there is not yet a single or set of biomarker(s) and technique(s) that is validated as providing the BA that reflects the best real aging status of individuals. Herein, a comprehensive overview of aging biomarkers is provided and the potential of genetic variations as proxy indicators of the aging state is highlighted. A comprehensive overview of BA estimation methods is also provided as well as a discussion of their performances, advantages, limitations, and potential approaches to overcome these limitations.
Effects of an aged tissue niche on the immune potency of dendritic cells using simulated microgravity
Authors: ElGindi Mei , Sapudom Jiranuwat , Garcia Sabate Anna , Chesney Quartey Brian , Alatoom Aseel , Al-Sayegh Mohamed , Li Rui , Chen Weiqiang , Teo Jeremy 
Published: July 2023

AbstractMicrogravity accelerates the aging of various physiological systems, and it is well acknowledged that aged individuals and astronauts both have increased susceptibility to infections and poor response to vaccination. Immunologically, dendritic cells (DCs) are the key players in linking innate and adaptive immune responses. Their distinct and optimized differentiation and maturation phases play a critical role in presenting antigens and mounting effective lymphocyte responses for long-term immunity. Despite their importance, no studies to date have effectively investigated the effects of microgravity on DCs in their native microenvironment, which is primarily located within tissues. Here, we address a significantly outstanding research gap by examining the effects of simulated microgravity via a random positioning machine on both immature and mature DCs cultured in biomimetic collagen hydrogels, a surrogate for tissue matrices. Furthermore, we explored the effects of loose and dense tissues via differences in collagen concentration. Under these various environmental conditions, the DC phenotype was characterized using surface markers, cytokines, function, and transcriptomic profiles. Our data indicate that aged or loose tissue and exposure to RPM-induced simulated microgravity both independently alter the immunogenicity of immature and mature DCs. Interestingly, cells cultured in denser matrices experience fewer effects of simulated microgravity at the transcriptome level. Our findings are a step forward to better facilitate healthier future space travel and enhance our understanding of the aging immune system on Earth.
Perspective on the current state of the LRRK2 field
Authors: Taymans Jean-Marc , Fell Matt , Greenamyre Tim , Hirst Warren D. , Mamais Adamantios , Padmanabhan Shalini , Peter Inga , Rideout Hardy , Thaler Avner 
Published: July 2023

AbstractAlmost 2 decades after linking LRRK2 to Parkinson’s disease, a vibrant research field has developed around the study of this gene and its protein product. Recent studies have begun to elucidate molecular structures of LRRK2 and its complexes, and our understanding of LRRK2 has continued to grow, affirming decisions made years ago to therapeutically target this enzyme for PD. Markers of LRRK2 activity, with potential to monitor disease progression or treatment efficacy, are also under development. Interestingly, there is a growing understanding of the role of LRRK2 outside of the central nervous system in peripheral tissues such as gut and immune cells that may also contribute to LRRK2 mediated pathology. In this perspective, our goal is to take stock of LRRK2 research by discussing the current state of knowledge and critical open questions in the field.
Chinese Soil Moisture Observation Network and Time Series Data Set for High Resolution Satellite Applications
Authors: Wang Chunmei , Gu Xingfa , Zhou Xiang , Yang Jian , Yu Tao , Tao Zui , Gao Hailiang , Liu Qiyue , Zhan Yulin , Wei Xiangqin , Li Juan , Zhang Lili , Li Lei , Li Bingze , Feng Zhuangzhuang , Wang Xigang , Fu Ruoxi , Zheng Xingming , Wang Chunnuan , Sun Yuan , Li Bin , Dong Wen 
Published: July 2023

AbstractHigh-quality ground observation networks are an important basis for scientific research. Here, an automatic soil observation network for high-resolution satellite applications in China (SONTE-China) was established to measure both pixel- and multilayer-based soil moisture and temperature. SONTE-China is distributed across 17 field observation stations with a variety of ecosystems, covering both dry and wet zones. In this paper, the average root mean squared error (RMSE) of station-based soil moisture for well-characterized SONTE-China sites is 0.027 m3/m3 (0.014~0.057 m3/m3) following calibration for specific soil properties. The temporal and spatial characteristics of the observed soil moisture and temperature in SONTE-China conform to the geographical location, seasonality and rainfall of each station. The time series Sentinel-1 C-band radar signal and soil moisture show strong correlations, and the RMSE of the estimated soil moisture from radar data was lower than 0.05 m3/m3 for the Guyuan and Minqin stations. SONTE-China is a soil moisture retrieval algorithm that can validate soil moisture products and provide basic data for weather forecasting, flood forecasting, agricultural drought monitoring and water resource management.
Mutational signatures reveal mutual exclusivity of homologous recombination and mismatch repair deficiencies in colorectal and stomach tumors
Authors: Farmanbar Amir , Kneller Robert , Firouzi Sanaz 
Published: July 2023

AbstractDecomposing somatic mutation spectra into mutational signatures and their corresponding etiologies provides a powerful approach for investigating the mechanism of DNA damage and repair. Assessing microsatellite (in)stability (MSI/MSS) status and interpreting their clinical relevance in different malignancies offers significant diagnostic and prognostic value. However, little is known about microsatellite (in)stability and its interactions with other DNA repair mechanisms such as homologous recombination (HR) in different cancer types. Based on whole-genome/exome mutational signature analysis, we showed HR deficiency (HRd) and mismatch repair deficiency (MMRd) occur in a significantly mutually exclusive manner in stomach and colorectal adenocarcinomas. ID11 signature with currently unknown etiology was prevalent in MSS tumors, co-occurred with HRd and was mutually exclusive with MMRd. Apolipoprotein B mRNA editing enzyme, Catalytic polypeptide-like (APOBEC) signature co-occurred with HRd and was mutually exclusive with MMRd in stomach tumors. The HRd signature in MSS tumors and the MMRd signature in MSI tumors were the first or second dominant signatures wherever detected. HRd may drive a distinct subgroup of MSS tumors and lead to poor clinical outcome. These analyses offer insight into mutational signatures in MSI and MMS tumors and reveal opportunities for improved clinical diagnosis and personalized treatment of MSS tumors.
Single cell RNA analysis of the left–right organizer transcriptome reveals potential novel heterotaxy genes
Authors: Bellchambers Helen M. , Phatak Amruta R. , Nenni Mardi J. , Padua Maria B. , Gao Hongyu , Liu Yunlong , Ware Stephanie M. 
Published: July 2023

AbstractThe establishment of left–right patterning in mice occurs at a transient structure called the embryonic node or left–right organizer (LRO). Previous analysis of the LRO has proven challenging due to the small cell number and transient nature of this structure. Here, we seek to overcome these difficulties to define the transcriptome of the LRO. Specifically, we used single cell RNA sequencing of 0–1 somite embryos to identify LRO enriched genes which were compared to bulk RNA sequencing of LRO cells isolated by fluorescent activated cell sorting. Gene ontology analysis indicated an enrichment of genes associated with cilia and laterality terms. Furthermore, comparison to previously identified LRO genes identified 127 novel LRO genes, including Ttll3, Syne1 and Sparcl1, for which the expression patterns were validated using whole mount in situ hybridization. This list of novel LRO genes will be a useful resource for further studies on LRO morphogenesis, the establishment of laterality and the genetic causes of heterotaxy.
Study on co-seismic ionospheric disturbance of Alaska earthquake on July 29, 2021 based on GPS TEC
Authors: Ruan Qingshan , Yuan Xitun , Liu Hang , Ge Shuyao 
Published: July 2023

AbstractWith the rapid development of space geodetic information technology, the Global Positioning System (GPS) has been widely used in seismology and space environmental research. Typically, the occurrence of a large earthquake will lead to some changes in the ionosphere, this phenomenon is called coseismic ionospheric disturbances (CIDs). In this contribution, differential slant total electron content (dSTEC) is used to study the anomalous characteristics of the ionosphere. First, based on the ionospheric dSTEC time series and two-dimensional disturbance detection, the temporal and spatial characteristics of ionospheric disturbances can be accurately analysed. Secondly, using wavelet transform spectrum analysis and disturbance propagation velocity, it can be determined that the disturbance sources of this earthquake can be identified as acoustic wave, gravity wave and Rayleigh wave. Finally, in order to further clarify the direction of the earthquake disturbance, this study focuses on proposing an innovative method for the disturbance propagation direction, and determines that there are two directions of the propagation of the CIDs of the Alaski earthquake.
3D-printing-assisted fabrication of hierarchically structured biomimetic surfaces with dual-wettability for water harvesting
Authors: Choi Yeongu , Baek Keuntae , So Hongyun 
Published: July 2023

AbstractFreshwater acquisition methods under various environments are required because water scarcity has intensified worldwide. Furthermore, as water is an essential resource for humans, a freshwater acquisition method that can be utilized even under harsh conditions, such as waterless and polluted water environments, is highly required. In this study, a three-dimensional (3D) printing-assisted hierarchically structured surface with dual-wettability (i.e., surface with both hydrophobic and hydrophilic region) for fog harvesting was developed by mimicking the biological features (i.e., cactus spines and elytra of Namib Desert beetles) that have effective characteristics for fog harvesting. The cactus-shaped surface exhibited self-transportation ability of water droplet, derived from the Laplace pressure gradient. Additionally, microgrooved patterns of the cactus spines were implemented using the staircase effect of 3D printing. Moreover, a partial metal deposition method using wax-based masking was introduced to realize the dual wettability of the elytra of the Namib Desert beetle. Consequently, the proposed surface exhibited the best performance (average weight of 7.85 g for 10 min) for fog harvesting, which was enhanced by the synergetic effect between the Laplace pressure gradient and surface energy gradient. These results support a novel freshwater production system that can be utilized even in harsh conditions, such as waterless and polluted water environments.
Coupling of nematic in-plane orientational ordering and equilibrium shapes of closed flexible nematic shells
Authors: Mesarec Luka , Góźdź Wojciech , Kralj-Iglič Veronika , Kralj Samo , Iglič Aleš 
Published: July 2023

AbstractThe impact of the intrinsic curvature of in-plane orientationally ordered curved flexible nematic molecules attached to closed 3D flexible shells was studied numerically. A Helfrich-Landau-de Gennes-type mesoscopic approach was adopted where the flexible shell’s curvature field and in-plane nematic field are coupled and concomitantly determined in the process of free energy minimisation. We demonstrate that this coupling has the potential to generate a rich diversity of qualitatively new shapes of closed 3D nematic shells and the corresponding specific in-plane orientational ordering textures, which strongly depend on the shell’s volume-to-surface area ratio, so far not predicted in mesoscopic-type numerical studies of 3D shapes of closed flexible nematic shells.