bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA UCA1 promotes keratinocyte-driven inflammation via suppressing METTL14 and activating the HIF-1α/NF-κB axis in psoriasis
Authors: Hu Yibo , Lei Li , Jiang Ling , Zeng Hongliang , Zhang Yushan , Fu Chuhan , Guo Haoran , Dong Yumeng , Ouyang Yujie , Zhang Xiaolin , Huang Jinhua , Zeng Qinghai , Chen Jing 
Published: April 2023

AbstractKeratinocytes are closely associated with innate immunity and inflammatory responses, and are dysregulated during the development of psoriasis, but the underlying mechanisms are not yet fully understood. This work aims to reveal the effects of long non-coding RNA (lncRNA) UCA1 in psoriatic keratinocytes. UCA1 was identified as a psoriasis-related lncRNA that highly expressed in psoriatic lesions. The transcriptome and proteome data of keratinocyte cell line HaCaT showed that UCA1 could positively regulate inflammatory functions, such as response to cytokine. Furthermore, UCA1 silencing decreased inflammatory cytokine secretion and innate immunity gene expression in HaCaT, its culture supernatant also decreased the migration and tube formation ability of vascular endothelial cells (HUVECs). Mechanistically, UCA1 activated the NF-κB signaling pathway, which is regulated by HIF-1α and STAT3. We also observed a direct interaction between UCA1 and N6-methyladenosine (m6A) methyltransferase METTL14. Knocking down METTL14 counteracted the effects of UCA1 silencing, indicating that it can suppress inflammation. In addition, the levels of m6A-modified HIF-1α were decreased in psoriatic lesions, indicating that HIF-1α is a potential target of METTL14. Taken together, this work indicates that UCA1 positively regulates keratinocyte-driven inflammation and psoriasis development by binding to METTL14, and activating HIF-1α and NF-κB signaling pathway. Our findings provide new insights into the molecular mechanisms of keratinocyte-driven inflammation in psoriasis.
Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma
Authors: Hao Jing , Han Xiangzi , Huang Haidong , Yu Xingjiang , Fang Jiankang , Zhao Jianjun , Prayson Richard A. , Bao Shideng , Yu Jennifer S. 
Published: April 2023

AbstractThe Wnt pathway is frequently dysregulated in many cancers, underscoring it as a therapeutic target. Wnt inhibitors have uniformly failed in clinical trials. Here, we report a mechanism of WNT pathway activation through the Semaphorin 3 C neurodevelopmental program in glioma stem-like cells. Sema3C directs β-catenin nuclear accumulation in a Rac1-dependent process, leading to transactivation of Wnt target genes. Sema3C-driven Wnt signaling occurred despite suppression of Wnt ligand secretion, suggesting that Sema3C drives canonical Wnt signaling independent of Wnt ligand binding. In a mouse model of glioblastoma, combined depletion of Sema3C and β-catenin partner TCF1 extended animal survival more than single target inhibition alone. In human glioblastoma, Sema3C expression and Wnt pathway activation were highly concordant. Since Sema3C is frequently overexpressed in glioblastoma, Sema3C signaling may be a significant mechanism of resistance to upstream Wnt pathway inhibitors. Dual targeting of Sema3C and Wnt pathways may achieve clinically significant Wnt pathway inhibition.
Evolution of cortical geometry and its link to function, behaviour and ecology
Authors: Schwartz Ernst , Nenning Karl-Heinz , Heuer Katja , Jeffery Nathan , Bertrand Ornella C. , Toro Roberto , Kasprian Gregor , Prayer Daniela , Langs Georg 
Published: April 2023

AbstractStudies in comparative neuroanatomy and of the fossil record demonstrate the influence of socio-ecological niches on the morphology of the cerebral cortex, but have led to oftentimes conflicting theories about its evolution. Here, we study the relationship between the shape of the cerebral cortex and the topography of its function. We establish a joint geometric representation of the cerebral cortices of ninety species of extant Euarchontoglires, including commonly used experimental model organisms. We show that variability in surface geometry relates to species’ ecology and behaviour, independent of overall brain size. Notably, ancestral shape reconstruction of the cortical surface and its change during evolution enables us to trace the evolutionary history of localised cortical expansions, modal segregation of brain function, and their association to behaviour and cognition. We find that individual cortical regions follow different sequences of area increase during evolutionary adaptations to dynamic socio-ecological niches. Anatomical correlates of this sequence of events are still observable in extant species, and relate to their current behaviour and ecology. We decompose the deep evolutionary history of the shape of the human cortical surface into spatially and temporally conscribed components with highly interpretable functional associations, highlighting the importance of considering the evolutionary history of cortical regions when studying their anatomy and function.
Interstitial lung disease diagnosis and prognosis using an AI system integrating longitudinal data
Authors: Mei Xueyan , Liu Zelong , Singh Ayushi , Lange Marcia , Boddu Priyanka , Gong Jingqi Q. X. , Lee Justine , DeMarco Cody , Cao Chendi , Platt Samantha , Sivakumar Ganesh , Gross Benjamin , Huang Mingqian , Masseaux Joy , Dua Sakshi , Bernheim Adam , Chung Michael , Deyer Timothy , Jacobi Adam , Padilla Maria , Fayad Zahi A. , Yang Yang 
Published: April 2023

AbstractFor accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient’s 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis.
Trumpet is an operating system for simple and robust cell-free biocomputing
Authors: Sharon Judee A. , Dasrath Chelsea , Fujiwara Aiden , Snyder Alessandro , Blank Mace , O’Brien Sam , Aufdembrink Lauren M. , Engelhart Aaron E. , Adamala Katarzyna P. 
Published: April 2023

AbstractBiological computation is becoming a viable and fast-growing alternative to traditional electronic computing. Here we present a biocomputing technology called Trumpet: Transcriptional RNA Universal Multi-Purpose GatE PlaTform. Trumpet combines the simplicity and robustness of the simplest in vitro biocomputing methods, adding signal amplification and programmability, while avoiding common shortcomings of live cell-based biocomputing solutions. We have demonstrated the use of Trumpet to build all universal Boolean logic gates. We have also built a web-based platform for designing Trumpet gates and created a primitive processor by networking several gates as a proof-of-principle for future development. The Trumpet offers a change of paradigm in biocomputing, providing an efficient and easily programmable biological logic gate operating system.
AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling
Authors: Da Xingwen , Li Ziyan , Huang Xiaofan , He Zuhan , Yu Yubing , Tian Tongtong , Xu Chengqi , Yao Yufeng , Wang Qing K. 
Published: April 2023

AbstractThoracic aortic aneurysm (TAA) is a localized or diffuse dilatation of the thoracic aortas, and causes many sudden deaths each year worldwide. However, there is no effective pharmacologic therapy. Here, we show that AGGF1 effectively blocks TAA-associated arterial inflammation and remodeling in three different mouse models (mice with transverse aortic constriction, Fbn1C1041G/+ mice, and β-aminopropionitrile-treated mice). AGGF1 expression is reduced in the ascending aortas from the three models and human TAA patients. Aggf1+/- mice and vascular smooth muscle cell (VSMC)-specific Aggf1smcKO knockout mice show aggravated TAA phenotypes. Mechanistically, AGGF1 enhances the interaction between its receptor integrin α7 and latency-associated peptide (LAP)-TGF-β1, blocks the cleavage of LAP-TGF-β1 to form mature TGF-β1, and inhibits Smad2/3 and ERK1/2 phosphorylation in VSMCs. Pirfenidone, a treatment agent for idiopathic pulmonary fibrosis, inhibits TAA-associated vascular inflammation and remodeling in wild type mice, but not in Aggf1+/- mice. In conclusion, we identify an innovative AGGF1 protein therapeutic strategy to block TAA-associated vascular inflammation and remodeling, and show that efficacy of TGF-β inhibition therapies require AGGF1.
RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function
Authors: Shiraishi Chisa , Matsumoto Akinobu , Ichihara Kazuya , Yamamoto Taishi , Yokoyama Takeshi , Mizoo Taisuke , Hatano Atsushi , Matsumoto Masaki , Tanaka Yoshikazu , Matsuura-Suzuki Eriko , Iwasaki Shintaro , Matsushima Shouji , Tsutsui Hiroyuki , Nakayama Keiichi I. 
Published: April 2023

AbstractAlthough several ribosomal protein paralogs are expressed in a tissue-specific manner, how these proteins affect translation and why they are required only in certain tissues have remained unclear. Here we show that RPL3L, a paralog of RPL3 specifically expressed in heart and skeletal muscle, influences translation elongation dynamics. Deficiency of RPL3L-containing ribosomes in RPL3L knockout male mice resulted in impaired cardiac contractility. Ribosome occupancy at mRNA codons was found to be altered in the RPL3L-deficient heart, and the changes were negatively correlated with those observed in myoblasts overexpressing RPL3L. RPL3L-containing ribosomes were less prone to collisions compared with RPL3-containing canonical ribosomes. Although the loss of RPL3L-containing ribosomes altered translation elongation dynamics for the entire transcriptome, its effects were most pronounced for transcripts related to cardiac muscle contraction and dilated cardiomyopathy, with the abundance of the encoded proteins being correspondingly decreased. Our results provide further insight into the mechanisms and physiological relevance of tissue-specific translational regulation.
Identifying high-impact variants and genes in exomes of Ashkenazi Jewish inflammatory bowel disease patients
Authors: Wu Yiming , Gettler Kyle , Kars Meltem Ece , Giri Mamta , Li Dalin , Bayrak Cigdem Sevim , Zhang Peng , Jain Aayushee , Maffucci Patrick , Sabic Ksenija , Van Vleck Tielman , Nadkarni Girish , Denson Lee A. , Ostrer Harry , Levine Adam P. , Schiff Elena R. , Segal Anthony W. , Kugathasan Subra , Stenson Peter D. , Cooper David N. , Philip Schumm L. , Snapper Scott , Daly Mark J. , Haritunians Talin , Duerr Richard H. , Silverberg Mark S. , Rioux John D. , Brant Steven R. , McGovern Dermot P. B. , Cho Judy H. , Itan Yuval 
Published: April 2023

AbstractInflammatory bowel disease (IBD) is a group of chronic digestive tract inflammatory conditions whose genetic etiology is still poorly understood. The incidence of IBD is particularly high among Ashkenazi Jews. Here, we identify 8 novel and plausible IBD-causing genes from the exomes of 4453 genetically identified Ashkenazi Jewish IBD cases (1734) and controls (2719). Various biological pathway analyses are performed, along with bulk and single-cell RNA sequencing, to demonstrate the likely physiological relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of Ashkenazi Jewish adult IBD displays significant overlap with very early onset-IBD genetics. Moreover, by performing biobank phenome-wide analyses, we find that IBD genes have pleiotropic effects that involve other immune responses. Finally, we show that polygenic risk score analyses based on genome-wide high impact variants have high power to predict IBD susceptibility.
LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism
Authors: He Xin-yu , Fan Xiao , Qu Lei , Wang Xiang , Jiang Li , Sang Ling-jie , Shi Cheng-yu , Lin Siyi , Yang Jie-cheng , Yang Zuo-zhen , Lei Kai , Li Jun-hong , Ju Huai-qiang , Yan Qingfeng , Liu Jian , Wang Fudi , Shao Jianzhong , Xiong Yan , Wang Wenqi , Lin Aifu 
Published: April 2023

AbstractIron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP,LncRIM(LncRNA Related to Iron Metabolism, also namedZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically,LncRIMdirectly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally,LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression ofLncRIMcorrelates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in whichLncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.
Atomic-scale observation of premelting at 2D lattice defects inside oxide crystals
Authors: Kim Hye-Sung , An Ji-Sang , Bae Hyung Bin , Chung Sung-Yoon 
Published: April 2023

AbstractSince two major criteria for melting were proposed by Lindemann and Born in the early 1900s, many simulations and observations have been carried out to elucidate the premelting phenomena largely at the crystal surfaces and grain boundaries below the bulk melting point. Although dislocations and clusters of vacancies and interstitials were predicted as possible origins to trigger the melting, experimental direct observations demonstrating the correlation of premelting with lattice defects inside a crystal remain elusive. Using atomic-column-resolved imaging with scanning transmission electron microscopy in polycrystalline BaCeO3, here we clarify the initiation of melting at two-dimensional faults inside the crystals below the melting temperature. In particular, melting in a layer-by-layer manner rather than random nucleation at the early stage was identified as a notable finding. Emphasizing the value of direct atomistic observation, our study suggests that lattice defects inside crystals should not be overlooked as preferential nucleation sites for phase transformation including melting.
Accelerated biological aging and risk of depression and anxiety: evidence from 424,299 UK Biobank participants
Authors: Gao Xu , Geng Tong , Jiang Meijie , Huang Ninghao , Zheng Yinan , Belsky Daniel W. , Huang Tao 
Published: April 2023

AbstractTheory predicts that biological processes of aging may contribute to poor mental health in late life. To test this hypothesis, we evaluated prospective associations between biological age and incident depression and anxiety in 424,299 UK Biobank participants. We measured biological age from clinical traits using the KDM-BA and PhenoAge algorithms. At baseline, participants who were biologically older more often experienced depression/anxiety. During a median of 8.7 years of follow-up, participants with older biological age were at increased risk of incident depression/anxiety (5.9% increase per standard deviation [SD] of KDM-BA acceleration, 95% confidence intervals [CI]: 3.3%–8.5%; 11.3% increase per SD of PhenoAge acceleration, 95% CI: 9.%–13.0%). Biological-aging-associated risk of depression/anxiety was independent of and additive to genetic risk measured by genome-wide-association-study-based polygenic scores. Advanced biological aging may represent a potential risk factor for incident depression/anxiety in midlife and older adults and a potential target for risk assessment and intervention.
Discovery and structural characterization of monkeypox virus methyltransferase VP39 inhibitors reveal similarities to SARS-CoV-2 nsp14 methyltransferase
Authors: Silhan Jan , Klima Martin , Otava Tomas , Skvara Petr , Chalupska Dominika , Chalupsky Karel , Kozic Jan , Nencka Radim , Boura Evzen 
Published: April 2023

AbstractMonkeypox is a disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a double-stranded DNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present crystal structures of its 2′-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin and a series of inhibitors that were discovered based on it. A comparison of this 2′-O-RNA MTase with enzymes from unrelated single-stranded RNA viruses (SARS-CoV-2 and Zika) reveals a conserved sinefungin binding mode, implicating that a single inhibitor could be used against unrelated viral families. Indeed, several of our inhibitors such as TO507 also inhibit the coronaviral nsp14 MTase.
DeepFLR facilitates false localization rate control in phosphoproteomics
Authors: Zong Yu , Wang Yuxin , Yang Yi , Zhao Dan , Wang Xiaoqing , Shen Chengpin , Qiao Liang 
Published: April 2023

AbstractProtein phosphorylation is a post-translational modification crucial for many cellular processes and protein functions. Accurate identification and quantification of protein phosphosites at the proteome-wide level are challenging, not least because efficient tools for protein phosphosite false localization rate (FLR) control are lacking. Here, we propose DeepFLR, a deep learning-based framework for controlling the FLR in phosphoproteomics. DeepFLR includes a phosphopeptide tandem mass spectrum (MS/MS) prediction module based on deep learning and an FLR assessment module based on a target-decoy approach. DeepFLR improves the accuracy of phosphopeptide MS/MS prediction compared to existing tools. Furthermore, DeepFLR estimates FLR accurately for both synthetic and biological datasets, and localizes more phosphosites than probability-based methods. DeepFLR is compatible with data from different organisms, instruments types, and both data-dependent and data-independent acquisition approaches, thus enabling FLR estimation for a broad range of phosphoproteomics experiments.
Structural insights into RNase J that plays an essential role in Mycobacterium tuberculosis RNA metabolism
Authors: Bao Luyao , Hu Juan , Zhan Bowen , Chi Mingzhe , Li Zhengyang , Wang Sen , Shan Chan , Zhao Zhaozhao , Guo Yanchao , Ding Xiaoming , Ji Chaoneng , Tao Shengce , Ni Ting , Zhang Xuelian , Zhao Guoping , Li Jixi 
Published: April 2023

AbstractRibonucleases (RNases) are responsible for RNA metabolism. RNase J, the core enzyme of the RNA degradosome, plays an essential role in global mRNA decay. Emerging evidence showed that the RNase J of Mycobacterium tuberculosis (Mtb-RNase J) could be an excellent target for treating Mtb infection. Here, crystal structures of Mtb-RNase J in apo-state and complex with the single-strand RNA reveal the conformational change upon RNA binding and hydrolysis. Mtb-RNase J forms an active homodimer through the interactions between the β-CASP and the β-lactamase domain. Knockout of RNase J slows the growth rate and changes the colony morphologies and cell length in Mycobacterium smegmatis, which is restored by RNase J complementation. Finally, RNA-seq analysis shows that the knockout strain significantly changes the expression levels of 49 genes in metabolic pathways. Thus, our current study explores the structural basis of Mtb-RNase J and might provide a promising candidate in pharmacological treatment for tuberculosis.
Uniform segmented platelet micelles with compositionally distinct and selectively degradable cores
Authors: Tong Zaizai , Xie Yujie , Arno Maria C. , Zhang Yifan , Manners Ian , O’Reilly Rachel K. , Dove Andrew P. 
Published: April 2023

AbstractThe creation of nanoparticles with controlled and uniform dimensions and spatially defined functionality is a key challenge. The recently developed living crystallization-driven self-assembly (CDSA) method has emerged as a promising route to one-dimensional (1D) and 2D core–shell micellar assemblies by seeded growth of polymeric and molecular amphiphiles. However, the general limitation of the epitaxial growth process to a single core-forming chemistry is an important obstacle to the creation of complex nanoparticles with segmented cores of spatially varied composition that can be subsequently exploited in selective transformations or responses to external stimuli. Here we report the successful use of a seeded growth approach that operates for a variety of different crystallizable polylactone homopolymer/block copolymer blend combinations to access 2D platelet micelles with compositionally distinct segmented cores. To illustrate the utility of controlling internal core chemistry, we demonstrate spatially selective hydrolytic degradation of the 2D platelets—a result that may be of interest for the design of complex stimuli-responsive particles for programmed-release and cargo-delivery applications.
Accurate structure models and absolute configuration determination using dynamical effects in continuous-rotation 3D electron diffraction data
Authors: Klar Paul B. , Krysiak Yaşar , Xu Hongyi , Steciuk Gwladys , Cho Jung , Zou Xiaodong , Palatinus Lukas 
Published: April 2023

AbstractContinuous-rotation 3D electron diffraction methods are increasingly popular for the structure analysis of very small organic molecular crystals and crystalline inorganic materials. Dynamical diffraction effects cause non-linear deviations from kinematical intensities that present issues in structure analysis. Here, a method for structure analysis of continuous-rotation 3D electron diffraction data is presented that takes multiple scattering effects into account. Dynamical and kinematical refinements of 12 compounds—ranging from small organic compounds to metal–organic frameworks to inorganic materials—are compared, for which the new approach yields significantly improved models in terms of accuracy and reliability with up to fourfold reduction of the noise level in difference Fourier maps. The intrinsic sensitivity of dynamical diffraction to the absolute structure is also used to assign the handedness of 58 crystals of 9 different chiral compounds, showing that 3D electron diffraction is a reliable tool for the routine determination of absolute structures.