bluuebunny/crossref_metadata_2025_split huggingface dataset:
N6-methyladenosine demethylase FTO promotes growth and metastasis of gastric cancer via m6A modification of caveolin-1 and metabolic regulation of mitochondrial dynamics
Authors: Zhou You , Wang Qi , Deng Haifeng , Xu Bin , Zhou Yi , Liu Jian , Liu Yingting , Shi Yufang , Zheng Xiao , Jiang Jingting 
Published: January 2022

AbstractGastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m6A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m6A in GC remains largely unknown, and the dysregulation of m6A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m6A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m6A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.
Estrogen receptor beta promotes lung cancer invasion via increasing CXCR4 expression
Authors: Liu Shiqing , Hu Chengping , Li Min , An Jian , Zhou Wolong , Guo Jia , Xiao Yao 
Published: January 2022

AbstractLung cancer is one of the most lethal malignant tumors in the world. The high recurrence and mortality rate make it urgent for scientists and clinicians to find new targets for better treatment of lung cancer. Early studies indicated that estrogen receptor β (ERβ) might impact the progression of non-small-cell lung cancer (NSCLC). However, the detailed mechanisms, especially its linkage to the CXCR4-mediated cell invasion, remain unclear. Here we found that ERβ could promote NSCLC cell invasion via increasing the circular RNA (circRNA), circ-TMX4, expression via directly binding to the 5′ promoter region of its host gene TMX4. ERβ-promoted circ-TMX4 could then sponge and inhibit the micro RNA (miRNA, miR), miR-622, expression, which can then result in increasing the CXCR4 messenger RNA translation via a reduced miRNA binding to its 3′ untranslated region (3′UTR). The preclinical study using an in vivo mouse model with orthotopic xenografts of NSCLC cells confirmed the in vitro data, and the human NSCLC database analysis and tissue staining also confirmed the linkage of ERβ/miR-622/CXCR4 signaling to the NSCLC progression. Together, our findings suggest that ERβ can promote NSCLC cell invasion via altering the ERβ/circ-TMX4/miR-622/CXCR4 signaling, and targeting this newly circ-TMX4/miR-622/CXCR4 signaling may help us find new treatment strategies to better suppress NSCLC progression.
RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m6A-dependent manner
Authors: Sun Shicheng , Gao Taihong , Pang Bo , Su Xiangsheng , Guo Changfa , Zhang Rui , Pang Qi 
Published: January 2022

AbstractFerroptosis is a form of cell death characterized by lipid peroxidation. Previous studies have reported that knockout of NF-κB activating protein (NKAP), an RNA-binding protein, increased lipid peroxidation level in naive T cells and induced cell death in colon cancer cells. However, there was no literature reported the relationship between NKAP and ferroptosis in glioblastoma cells. Notably, the mechanism of NKAP modulating ferroptosis is still unknown. Here, we found NKAP knockdown induced cell death in glioblastoma cells. Silencing NKAP increased the cell sensitivity to ferroptosis inducers both in vitro and in vivo. Exogenous overexpression of NKAP promoted cell resistance to ferroptosis inducers by positively regulating a ferroptosis defense protein, namely cystine/glutamate antiporter (SLC7A11). The regulation of SLC7A11 by NKAP can be weakened by the m6A methylation inhibitor cycloleucine and knockdown of the m6A writer METTL3. NKAP combined the “RGAC” motif which was exactly in line with the m6A motif “RGACH” (R = A/G, H = A/U/C) uncovered by the m6A-sequence. RNA Immunoprecipitation (RIP) and Co-Immunoprecipitation (Co-IP) proved the interaction between NKAP and m6A on SLC7A11 transcript. Following its binding to m6A, NKAP recruited the splicing factor proline and glutamine-rich (SFPQ) to recognize the splice site and then conducted transcription termination site (TTS) splicing event on SLC7A11 transcript and the retention of the last exon, screened by RNA-sequence and Mass Spectrometry (MS). In conclusion, NKAP acted as a new ferroptosis suppressor by binding to m6A and then promoting SLC7A11 mRNA splicing and maturation.
3D micromesh-based hybrid bioprinting: multidimensional liquid patterning for 3D microtissue engineering
Authors: Lee Byungjun , Kim Suryong , Ko Jihoon , Lee Seung-Ryeol , Kim Youngtaek , Park Seonghyuk , Kim Jiho , Hyung Sujin , Kim Ho-Young , Jeon Noo Li 
Published: January 2022

AbstractBioprinting has been widely used to fabricate tissue engineering scaffolds and develop in vitro tissue/tumor models. Bioprinting has enabled the fabrication of complex 3D structures using different polymers and hydrogels. However, relatively low resolution and long fabrication times due to the extrusion process has resulted in limited practices for cell-based applications. Here, we present a 3D hybrid-micromesh assisted bioprinting (Hy-MAP) method that combines digital light projection (DLP) 3D-printed micromesh scaffold structures and sequential hydrogel patterning. This novel method of bioprinting enables rapid cell coculture through the allowance of various methods, including injection, dipping and draining. This approach enables the construction of mesoscale (1-50 mm) complex 3D hydrogel structures by extending the micropost-based patterning that has been demonstrated in 2D microfluidic channels to 3D channel networks. We established the design rules for Hy-MAP through both analytical and experimental investigations of the capillary bursting pressure (CBP) dependence on the size and geometry of the mesh as well as other physical parameters. Vascularized tumor spheroids were formed with Hy-MAP by culturing endothelial cells, stromal cell mixtures and tumor spheroids inside separate but adjacent compartments. The novel approach described in this work will provide an alternative method for fabricating mesoscale implantable tissue engineering constructs and organ-on-a-chip applications.
Emerging spin–phonon coupling through cross-talk of two magnetic sublattices
Authors: Weber Mads C. , Guennou Mael , Evans Donald M. , Toulouse Constance , Simonov Arkadiy , Kholina Yevheniia , Ma Xiaoxuan , Ren Wei , Cao Shixun , Carpenter Michael A. , Dkhil Brahim , Fiebig Manfred , Kreisel Jens 
Published: January 2022

AbstractMany material properties such as superconductivity, magnetoresistance or magnetoelectricity emerge from the non-linear interactions of spins and lattice/phonons. Hence, an in-depth understanding of spin–phonon coupling is at the heart of these properties. While most examples deal with one magnetic lattice only, the simultaneous presence of multiple magnetic orderings yield potentially unknown properties. We demonstrate a strong spin–phonon coupling in SmFeO3 that emerges from the interaction of both, iron and samarium spins. We probe this coupling as a remarkably large shift of phonon frequencies and the appearance of new phonons. The spin–phonon coupling is absent for the magnetic ordering of iron alone but emerges with the additional ordering of the samarium spins. Intriguingly, this ordering is not spontaneous but induced by the iron magnetism. Our findings show an emergent phenomenon from the non-linear interaction by multiple orders, which do not need to occur spontaneously. This allows for a conceptually different approach in the search for yet unknown properties.
Self-assembly and photoinduced fabrication of conductive nanographene wires on boron nitride
Authors: Zhang Xiaoxi , Gärisch Fabian , Chen Zongping , Hu Yunbin , Wang Zishu , Wang Yan , Xie Liming , Chen Jianing , Li Juan , Barth Johannes V. , Narita Akimitsu , List-Kratochvil Emil , Müllen Klaus , Palma Carlos-Andres 
Published: January 2022

AbstractManufacturing molecule-based functional elements directly at device interfaces is a frontier in bottom-up materials engineering. A longstanding challenge in the field is the covalent stabilization of pre-assembled molecular architectures to afford nanodevice components. Here, we employ the controlled supramolecular self-assembly of anthracene derivatives on a hexagonal boron nitride sheet, to generate nanographene wires through photo-crosslinking and thermal annealing. Specifically, we demonstrate µm-long nanowires with an average width of 200 nm, electrical conductivities of 106 S m−1 and breakdown current densities of 1011 A m−2. Joint experiments and simulations reveal that hierarchical self-assembly promotes their formation and functional properties. Our approach demonstrates the feasibility of combined bottom-up supramolecular templating and top-down manufacturing protocols for graphene nanomaterials and interconnects, towards integrated carbon nanodevices.
Tissue-specific multi-omics analysis of atrial fibrillation
Authors: Assum Ines , Krause Julia , Scheinhardt Markus O. , Müller Christian , Hammer Elke , Börschel Christin S. , Völker Uwe , Conradi Lenard , Geelhoed Bastiaan , Zeller Tanja , Schnabel Renate B. , Heinig Matthias 
Published: January 2022

AbstractGenome-wide association studies (GWAS) for atrial fibrillation (AF) have uncovered numerous disease-associated variants. Their underlying molecular mechanisms, especially consequences for mRNA and protein expression remain largely elusive. Thus, refined multi-omics approaches are needed for deciphering the underlying molecular networks. Here, we integrate genomics, transcriptomics, and proteomics of human atrial tissue in a cross-sectional study to identify widespread effects of genetic variants on both transcript (cis-eQTL) and protein (cis-pQTL) abundance. We further establish a novel targeted trans-QTL approach based on polygenic risk scores to determine candidates for AF core genes. Using this approach, we identify two trans-eQTLs and five trans-pQTLs for AF GWAS hits, and elucidate the role of the transcription factor NKX2-5 as a link between the GWAS SNP rs9481842 and AF. Altogether, we present an integrative multi-omics method to uncover trans-acting networks in small datasets and provide a rich resource of atrial tissue-specific regulatory variants for transcript and protein levels for cardiovascular disease gene prioritization.
Adenosine receptor 2a agonists target mouse CD11c+T-bet+ B cells in infection and autoimmunity
Authors: Levack Russell C. , Newell Krista L. , Cabrera-Martinez Berenice , Cox Justin , Perl Andras , Bastacky Sheldon I. , Winslow Gary M. 
Published: January 2022

AbstractCD11c+T-bet+ B cells are recognized as an important component of humoral immunity and autoimmunity. These cells can be distinguished from other B cells by their higher expression of the adenosine receptor 2a. Here we address whether A2A receptor activation can affect CD11c+T-bet+ B cells. We show that administration of the A2A receptor agonist CGS-21680 depletes established CD11c+T-bet+ B cells in ehrlichial-infected mice, in a B cell-intrinsic manner. Agonist treatment similarly depletes CD11c+T-bet+ B cells and CD138+ B cells and reduces anti-nuclear antibodies in lupus-prone mice. Agonist treatment is also associated with reduced kidney pathology and lymphadenopathy. Moreover, A2A receptor stimulation depletes pathogenic lymphocytes and ameliorates disease even after disease onset, highlighting the therapeutic potential of this treatment. This study suggests that targeting the adenosine signaling pathway may provide a method for the treatment of lupus and other autoimmune diseases mediated by T-bet+ B cells.
f-electron hybridised Fermi surface in magnetic field-induced metallic YbB12
Authors: Liu H. , Hickey A. J. , Hartstein M. , Davies A. J. , Eaton A. G. , Elvin T. , Polyakov E. , Vu T. H. , Wichitwechkarn V. , Förster T. , Wosnitza J. , Murphy T. P. , Shitsevalova N. , Johannes M. D. , Hatnean M. Ciomaga , Balakrishnan G. , Lonzarich G. G. , Sebastian Suchitra E. 
Published: January 2022

AbstractThe nature of the Fermi surface observed in the recently discovered family of unconventional insulators starting with SmB6 is a subject of intense inquiry. Here we shed light on this question by accessing quantum oscillations in the high magnetic field-induced metallic regime above ≈47 T in YbB12, which we compare with the unconventional insulating regime. In the field-induced metallic regime, we find prominent quantum oscillations in the electrical resistivity characterised by multiple frequencies and heavy effective masses. The close similarity in Lifshitz-Kosevich low-temperature growth of quantum oscillation amplitude in insulating YbB12 to field-induced metallic YbB12, points to an origin of quantum oscillations in insulating YbB12 from in-gap neutral low energy excitations. Higher frequency Fermi surface sheets of heavy quasiparticle effective mass emerge in the field-induced metallic regime of YbB12 in addition to multiple heavy Fermi surface sheets observed in both insulating and metallic regimes. f-electron hybridisation is thus observed to persist from the unconventional insulating to the field-induced metallic regime of YbB12, in contrast to the unhybridised conduction electron Fermi surface observed in unconventional insulating SmB6. Our findings thus require an alternative model for YbB12, of neutral in-gap low energy excitations, wherein the f-electron hybridisation is retained.
Identification of differentially methylated genes in first-trimester placentas with trisomy 16
Authors: Tolmacheva Ekaterina N. , Vasilyev Stanislav A. , Nikitina Tatiana V. , Lytkina Ekaterina S. , Sazhenova Elena A. , Zhigalina Daria I. , Vasilyeva Oksana Yu. , Markov Anton V. , Demeneva Victoria V. , Tashireva Liubov A. , Kashevarova Anna A. , Lebedev Igor N. 
Published: January 2022

AbstractThe presence of an extra chromosome in the embryo karyotype often dramatically affects the fate of pregnancy. Trisomy 16 is the most common aneuploidy in first-trimester miscarriages. The present study identified changes in DNA methylation in chorionic villi of miscarriages with trisomy 16. Ninety-seven differentially methylated sites in 91 genes were identified (false discovery rate (FDR) < 0.05 and Δβ > 0.15) using DNA methylation arrays. Most of the differentially methylated genes encoded secreted proteins, signaling peptides, and receptors with disulfide bonds. Subsequent analysis using targeted bisulfite massive parallel sequencing showed hypermethylation of the promoters of specific genes in miscarriages with trisomy 16 but not miscarriages with other aneuploidies. Some of the genes were responsible for the development of the placenta and embryo (GATA3-AS1, TRPV6, SCL13A4, and CALCB) and the formation of the mitotic spindle (ANKRD53). Hypermethylation of GATA3-AS1 was associated with reduced expression of GATA3 protein in chorionic villi of miscarriages with trisomy 16. Aberrant hypermethylation of genes may lead to a decrease in expression, impaired trophoblast differentiation and invasion, mitotic disorders, chromosomal mosaicism and karyotype self-correction via trisomy rescue mechanisms.
Unique high Arctic methane metabolizing community revealed through in situ 13CH4-DNA-SIP enrichment in concert with genome binning
Authors: Altshuler Ianina , Raymond-Bouchard Isabelle , Magnuson Elisse , Tremblay Julien , Greer Charles W. , Whyte Lyle G. 
Published: January 2022

AbstractGreenhouse gas (GHG) emissions from Arctic permafrost soils create a positive feedback loop of climate warming and further GHG emissions. Active methane uptake in these soils can reduce the impact of GHG on future Arctic warming potential. Aerobic methane oxidizers are thought to be responsible for this apparent methane sink, though Arctic representatives of these organisms have resisted culturing efforts. Here, we first used in situ gas flux measurements and qPCR to identify relative methane sink hotspots at a high Arctic cytosol site, we then labeled the active microbiome in situ using DNA Stable Isotope Probing (SIP) with heavy13CH4(at 100 ppm and 1000 ppm). This was followed by amplicon and metagenome sequencing to identify active organisms involved in CH4metabolism in these high Arctic cryosols. Sequencing of13C-labeledpmoAgenes demonstrated that type II methanotrophs (Methylocapsa) were overall the dominant active methane oxidizers in these mineral cryosols, while type I methanotrophs (Methylomarinovum) were only detected in the 100 ppm SIP treatment. From the SIP-13C-labeled DNA, we retrieved nine high to intermediate quality metagenome-assembled genomes (MAGs) belonging to theProteobacteria,Gemmatimonadetes, andChloroflexi, with three of these MAGs containing genes associated with methanotrophy. A novelChloroflexiMAG contained ammoXgene along with other methane oxidation pathway genes, identifying it as a potential uncultured methane oxidizer. This MAG also contained genes for copper import, synthesis of biopolymers, mercury detoxification, and ammonia uptake, indicating that this bacterium is strongly adapted to conditions in active layer permafrost and providing new insights into methane biogeochemical cycling. In addition,BetaproteobacterialMAGs were also identified as potential cross-feeders with methanotrophs in these Arctic cryosols. Overall, in situ SIP labeling combined with metagenomics and genome binning demonstrated to be a useful tool for discovering and characterizing novel organisms related to specific microbial functions or biogeochemical cycles of interest. Our findings reveal a unique and active Arctic cryosol microbial community potentially involved in CH4cycling.
SPHARM-PDM based image preprocessing pipeline for quantitative morphometric analysis (QMA) for in situ joint assessment in rabbit and rat models
Authors: Durongbhan Pholpat , Davey Catherine E. , Stok Kathryn S. 
Published: January 2022

AbstractThe accessibility of quantitative measurements of joint morphometry depends on appropriate tibial alignment and volume of interest (VOI) selection of joint compartments; often a challenging and time-consuming manual task. In this work, we developed a novel automatic, efficient, and model-invariant image preprocessing pipeline that allows for highly reproducible 3D quantitative morphometric analysis (QMA) of the joint. The pipeline addresses the problem by deploying two modules: an alignment module and a subdivision module. Alignment is achieved by representing the tibia in its basic form using lower degree spherical harmonic basis functions and aligning using principal component analysis. The second module subdivides the joint into lateral and medial VOIs via a watershedding approach based on persistence homology. Multiple repeated micro-computed tomography scans of small (rat) and medium (rabbit) animal knees were processed using the pipeline to demonstrate model invariance. Existing QMA was performed to evaluate the pipeline’s ability to generate reproducible measurements. Intraclass correlation coefficient and mean-normalised root-mean-squared error of more than 0.75 and lower than 9.5%, respectively, were achieved for joint centre of mass, joint contact area under virtual loading, joint space width, and joint space volume. Processing time and technical requirements were reduced compared to manual processing in previous studies.
Assessing the potential of native ecotypes of Poa pratensis L. for forage yield and phytochemical compositions under water deficit conditions
Authors: Shariatipour Nikwan , Heidari Bahram , Shams Zahra , Richards Christopher 
Published: January 2022

AbstractEvaluation of forage yield and antioxidant activity in Poa pratensis with high quality and good spring green-up forage might help variety improvement for use under water deficit condition. Germplasm and phenotypic diversity evaluations lay a foundation for genotype selection and improvement of varieties for drought tolerance in P. pratensis. The present study was conducted to assess the genetic potential of a collection of P. pratensis accessions for drought stress and to identify the association between polyphenol compounds and forage yield traits. Vegetative clone samples of 100 accessions collected from a diverse geographical area of Iran were clonally propagated in a greenhouse and evaluated in the field under two moisture regimes (non-stress and drought stress) in 2018 and 2019. Drought stress had negative effects on fresh and dry forage yields and reduced phenotypic variances. On average, drought stress reduced fresh and dry forage yields by 45% and 28%, respectively. The results of Mantel test showed no significant correlation between forage yield traits and geographical distances. Genetic coefficients of variation for forage yield and most of the phytochemicals were lower under drought stress, suggesting that deficit irrigation may reduce genetic variation for the tested traits. The estimates of heritability were higher under non-stress conditions than under drought stress treatment for forage yield traits and few polyphenols. However, the majority of polyphenol compounds had higher heritability than forage yield traits under drought stress, which suggests the potential for indirect selection. The ‘Ciakhor’, ‘Damavand’, ‘Karvandan’, ‘Abrumand’, and ‘Abr2’ accessions had high quantities for polyphenols and yield traits under both moisture regimes. These accessions are promising candidates for use in variety crossing programs and for developing high-yielding varieties under water-deficit conditions.
Performance comparison of different classification algorithms applied to the diagnosis of familial hypercholesterolemia in paediatric subjects
Authors: Albuquerque João , Medeiros Ana Margarida , Alves Ana Catarina , Bourbon Mafalda , Antunes Marília 
Published: January 2022

AbstractFamilial Hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, characterized by increased low density lipoprotein cholesterol (LDLc) levels. The main purpose of the current work was to explore alternative classification methods to traditional clinical criteria for FH diagnosis, based on several biochemical and biological indicators. Logistic regression (LR), decision tree (DT), random forest (RF) and naive Bayes (NB) algorithms were developed for this purpose, and thresholds were optimized by maximization of Youden index (YI). All models presented similar accuracy (Acc), specificity (Spec) and positive predictive values (PPV). Sensitivity (Sens) and G-mean values were significantly higher in LR and RF models, compared to the DT. When compared to Simon Broome (SB) biochemical criteria for FH diagnosis, all models presented significantly higher Acc, Spec and G-mean values (p < 0.01), and lower negative predictive value (NPV, p < 0.05). Moreover, LR and RF models presented comparable Sens values. Adjustment of the cut-off point by maximizing YI significantly increased Sens values, with no significant loss in Acc. The obtained results suggest such classification algorithms can be a viable alternative to be used as a widespread screening method. An online application has been developed to assess the performance of the LR model in a wider population.