bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients
Authors: Wang Zhilong , Liu Yang , Liu Jingyu , Kong Na , Jiang Yue , Jiang Ruiwei , Zhen Xin , Zhou Jidong , Li Chaojun , Sun Haixiang , Yan Guijun 
Published: April 2021

AbstractDecidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.
Functional cooperation between ASK1 and p21Waf1/Cip1 in the balance of cell-cycle arrest, cell death and tumorigenesis of stressed keratinocytes
Authors: De Blasio Carlo , Verma Nagendra , Moretti Marta , Cialfi Samantha , Zonfrilli Azzurra , Franchitto Matteo , Truglio Federica , De Smaele Enrico , Ichijo Hidenori , Naguro Isao , Screpanti Isabella , Talora Claudio 
Published: April 2021

AbstractBoth CDKN1A (p21 Waf1/Cip1) and Apoptosis signal-regulating kinase 1 (ASK1) play important roles in tumorigenesis. The role of p21 Waf1/Cip1 in attenuating ASK1-induced apoptosis by various stress conditions is well established. However, how ASK1 and p21 Waf1/Cip1 functionally interact during tumorigenesis is still unclear. To address this aspect, we crossed ASK1 knockout (ASK1KO) mice with p21Waf1/Cip1 knockout (p21KO) mice to compare single and double-mutant mice. We observed that deletion of p21Waf1/Cip1 leads to increased keratinocyte proliferation but also increased cell death. This is mechanistically linked to the ASK1 axis-induced apoptosis, including p38 and PARP. Indeed, deletion of ASK1 does not alter the proliferation but decreases the apoptosis of p21KO keratinocytes. To analyze as this interaction might affect skin carcinogenesis, we investigated the response of ASK1KO and p21KO mice to DMBA/TPA-induced tumorigenesis. Here we show that while endogenous ASK1 is dispensable for skin homeostasis, ASK1KO mice are resistant to DMBA/TPA-induced tumorigenesis. However, we found that epidermis lacking both p21 and ASK1 reacquires increased sensitivity to DMBA/TPA-induced tumorigenesis. We demonstrate that apoptosis and cell-cycle progression in p21KO keratinocytes are uncoupled in the absence of ASK1. These data support the model that a critical event ensuring the balance between cell death, cell-cycle arrest, and successful divisions in keratinocytes during stress conditions is the p21-dependent ASK1 inactivation.
Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling
Authors: Hu Qingtao , Hong Yu , Qi Pan , Lu Guangqing , Mai Xueying , Xu Sheng , He Xiaoying , Guo Yu , Gao Linlin , Jing Zhiyi , Wang Jiawen , Cai Tao , Zhang Yu 
Published: April 2021

AbstractTo gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
Protein kinase A controls the hexosamine pathway by tuning the feedback inhibition of GFAT-1
Authors: Ruegenberg Sabine , Mayr Felix A. M. C. , Atanassov Ilian , Baumann Ulrich , Denzel Martin S. 
Published: April 2021

AbstractThe hexosamine pathway (HP) is a key anabolic pathway whose product uridine 5’-diphospho-N-acetyl-D-glucosamine (UDP-GlcNAc) is an essential precursor for glycosylation processes in mammals. It modulates the ER stress response and HP activation extends lifespan in Caenorhabditis elegans. The highly conserved glutamine fructose-6-phosphate amidotransferase 1 (GFAT-1) is the rate-limiting HP enzyme. GFAT-1 activity is modulated by UDP-GlcNAc feedback inhibition and via phosphorylation by protein kinase A (PKA). Molecular consequences of GFAT-1 phosphorylation, however, remain poorly understood. Here, we identify the GFAT-1 R203H substitution that elevates UDP-GlcNAc levels in C. elegans. In human GFAT-1, the R203H substitution interferes with UDP-GlcNAc inhibition and with PKA-mediated Ser205 phosphorylation. Our data indicate that phosphorylation affects the interactions of the two GFAT-1 domains to control catalytic activity. Notably, Ser205 phosphorylation has two discernible effects: it lowers baseline GFAT-1 activity and abolishes UDP-GlcNAc feedback inhibition. PKA controls the HP by uncoupling the metabolic feedback loop of GFAT-1.
Short-term interaction between silent and devastating earthquakes in Mexico
Authors: Cruz-Atienza V. M. , Tago J. , Villafuerte C. , Wei M. , Garza-Girón R. , Dominguez L. A. , Kostoglodov V. , Nishimura T. , Franco S. I. , Real J. , Santoyo M. A. , Ito Y. , Kazachkina E. 
Published: April 2021

AbstractEither the triggering of large earthquakes on a fault hosting aseismic slip or the triggering of slow slip events (SSE) by passing seismic waves involve seismological questions with important hazard implications. Just a few observations plausibly suggest that such interactions actually happen in nature. In this study we show that three recent devastating earthquakes in Mexico are likely related to SSEs, describing a cascade of events interacting with each other on a regional scale via quasi-static and/or dynamic perturbations across the states of Guerrero and Oaxaca. Such interaction seems to be conditioned by the transient memory of Earth materials subject to the “traumatic” stress produced by seismic waves of the great 2017 (Mw8.2) Tehuantepec earthquake, which strongly disturbed the SSE cycles over a 650 km long segment of the subduction plate interface. Our results imply that seismic hazard in large populated areas is a short-term evolving function of seismotectonic processes that are often observable.
Genetic evidence for the association between COVID-19 epidemic severity and timing of non-pharmaceutical interventions
Authors: Ragonnet-Cronin Manon , Boyd Olivia , Geidelberg Lily , Jorgensen David , Nascimento Fabricia F. , Siveroni Igor , Johnson Robert A. , Baguelin Marc , Cucunubá Zulma M. , Jauneikaite Elita , Mishra Swapnil , Watson Oliver J. , Ferguson Neil , Cori Anne , Donnelly Christl A. , Volz Erik 
Published: April 2021

AbstractUnprecedented public health interventions including travel restrictions and national lockdowns have been implemented to stem the COVID-19 epidemic, but the effectiveness of non-pharmaceutical interventions is still debated. We carried out a phylogenetic analysis of more than 29,000 publicly available whole genome SARS-CoV-2 sequences from 57 locations to estimate the time that the epidemic originated in different places. These estimates were examined in relation to the dates of the most stringent interventions in each location as well as to the number of cumulative COVID-19 deaths and phylodynamic estimates of epidemic size. Here we report that the time elapsed between epidemic origin and maximum intervention is associated with different measures of epidemic severity and explains 11% of the variance in reported deaths one month after the most stringent intervention. Locations where strong non-pharmaceutical interventions were implemented earlier experienced much less severe COVID-19 morbidity and mortality during the period of study.
The landscape of molecular chaperones across human tissues reveals a layered architecture of core and variable chaperones
Authors: Shemesh Netta , Jubran Juman , Dror Shiran , Simonovsky Eyal , Basha Omer , Argov Chanan , Hekselman Idan , Abu-Qarn Mehtap , Vinogradov Ekaterina , Mauer Omry , Tiago Tatiana , Carra Serena , Ben-Zvi Anat , Yeger-Lotem Esti 
Published: April 2021

AbstractThe sensitivity of the protein-folding environment to chaperone disruption can be highly tissue-specific. Yet, the organization of the chaperone system across physiological human tissues has received little attention. Through computational analyses of large-scale tissue transcriptomes, we unveil that the chaperone system is composed of core elements that are uniformly expressed across tissues, and variable elements that are differentially expressed to fit with tissue-specific requirements. We demonstrate via a proteomic analysis that the muscle-specific signature is functional and conserved. Core chaperones are significantly more abundant across tissues and more important for cell survival than variable chaperones. Together with variable chaperones, they form tissue-specific functional networks. Analysis of human organ development and aging brain transcriptomes reveals that these functional networks are established in development and decline with age. In this work, we expand the known functional organization of de novo versus stress-inducible eukaryotic chaperones into a layered core-variable architecture in multi-cellular organisms.
Two-dimensional TIRF-SIM–traction force microscopy (2D TIRF-SIM-TFM)
Authors: Barbieri Liliana , Colin-York Huw , Korobchevskaya Kseniya , Li Di , Wolfson Deanna L. , Karedla Narain , Schneider Falk , Ahluwalia Balpreet S. , Seternes Tore , Dalmo Roy A. , Dustin Michael L. , Li Dong , Fritzsche Marco 
Published: April 2021

AbstractQuantifying small, rapidly evolving forces generated by cells is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. Traction force microscopy remains one of the most broadly applied force probing technologies but typically restricts itself to slow events over seconds and micron-scale displacements. Here, we improve >2-fold spatially and >10-fold temporally the resolution of planar cellular force probing compared to its related conventional modalities by combining fast two-dimensional total internal reflection fluorescence super-resolution structured illumination microscopy and traction force microscopy. This live-cell 2D TIRF-SIM-TFM methodology offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology to analysis.
Go Get Data (GGD) is a framework that facilitates reproducible access to genomic data
Authors: Cormier Michael J. , Belyeu Jonathan R. , Pedersen Brent S. , Brown Joseph , Köster Johannes , Quinlan Aaron R. 
Published: April 2021

AbstractThe rapid increase in the amount of genomic data provides researchers with an opportunity to integrate diverse datasets and annotations when addressing a wide range of biological questions. However, genomic datasets are deposited on different platforms and are stored in numerous formats from multiple genome builds, which complicates the task of collecting, annotating, transforming, and integrating data as needed. Here, we developed Go Get Data (GGD) as a fast, reproducible approach to installing standardized data recipes. GGD is available on Github (https://gogetdata.github.io/), is extendable to other data types, and can streamline the complexities typically associated with data integration, saving researchers time and improving research reproducibility.
Regulation of Arabidopsis photoreceptor CRY2 by two distinct E3 ubiquitin ligases
Authors: Chen Yadi , Hu Xiaohua , Liu Siyuan , Su Tiantian , Huang Hsiaochi , Ren Huibo , Gao Zhensheng , Wang Xu , Lin Deshu , Wohlschlegel James A. , Wang Qin , Lin Chentao 
Published: April 2021

AbstractCryptochromes (CRYs) are photoreceptors or components of the molecular clock in various evolutionary lineages, and they are commonly regulated by polyubiquitination and proteolysis. Multiple E3 ubiquitin ligases regulate CRYs in animal models, and previous genetics study also suggest existence of multiple E3 ubiquitin ligases for plant CRYs. However, only one E3 ligase, Cul4COP1/SPAs, has been reported for plant CRYs so far. Here we show that Cul3LRBs is the second E3 ligase of CRY2 in Arabidopsis. We demonstrate the blue light-specific and CRY-dependent activity of LRBs (Light-Response Bric-a-Brack/Tramtrack/Broad 1, 2 & 3) in blue-light regulation of hypocotyl elongation. LRBs physically interact with photoexcited and phosphorylated CRY2, at the CCE domain of CRY2, to facilitate polyubiquitination and degradation of CRY2 in response to blue light. We propose that Cul4COP1/SPAs and Cul3LRBs E3 ligases interact with CRY2 via different structure elements to regulate the abundance of CRY2 photoreceptor under different light conditions, facilitating optimal photoresponses of plants grown in nature.
A generalized density-modulated twist-splay-bend phase of banana-shaped particles
Authors: Chiappini Massimiliano , Dijkstra Marjolein 
Published: April 2021

AbstractIn 1976, Meyer predicted that bend distortions of the nematic director field are complemented by deformations of either twist or splay, yielding twist-bend and splay-bend nematic phases, respectively. Four decades later, the existence of the splay-bend nematic phase remains dubious, and the origin of these spontaneous distortions uncertain. Here, we conjecture that bend deformations of the nematic director can be complemented by simultaneous distortions of both twist and splay, yielding a twist-splay-bend nematic phase. Using theory and simulations, we show that the coupling between polar order and bend deformations drives the formation of modulated phases in systems of curved rods. We find that twist-bend phases transition to splay-bend phases via intermediate twist-splay-bend phases, and that splay distortions are always accompanied by periodic density modulations due to the coupling of the particle curvature with the non-uniform curvature of the splayed director field, implying that the twist-splay-bend and splay-bend phases of banana-shaped particles are actually smectic phases.
Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer
Authors: Weng Rueyhung R. , Lu Hsuan-Hsuan , Lin Chien-Ting , Fan Chia-Chi , Lin Rong-Shan , Huang Tai-Chung , Lin Shu-Yung , Huang Yi-Jhen , Juan Yi-Hsiu , Wu Yi-Chieh , Hung Zheng-Ci , Liu Chi , Lin Xuan-Hui , Hsieh Wan-Chen , Chiu Tzu-Yuan , Liao Jung-Chi , Chiu Yen-Ling , Chen Shih-Yu , Yu Chong-Jen , Tsai Hsing-Chen 
Published: April 2021

Abstractγδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.
Fire-induced rock spalling as a mechanism of weathering responsible for flared slope and inselberg development
Authors: Buckman Solomon , Morris Rowena H. , Bourman Robert P. 
Published: April 2021

AbstractInselbergs, such as Uluru in central Australia, are iconic landscape features of semi-arid and deeply denuded continental interiors. These islands of rock are commonly skirted by steep, overhanging cliffs (flared slopes) at ground level. The weathering processes responsible for formation of flared slopes and steep-sided inselbergs in flat, planated landscapes are enigmatic. One model emphasizes sub-surface weathering followed by denudation and excavation of saprolite to expose the unweathered bedrock while other models advocate slope development under subaerial conditions at ground level. We present a new hypothesis that identifies wildfire as a primary agent of flared slope development via fire-induced rock spalling around the periphery of inselbergs. Widespread fire-spalling following the 2019–2020 Australian fires illustrates that this is a common form of physical weathering in fire-prone environments but its effects are particularly evident in semi-arid regions where lateral fire-spalling dominates over fluvial and chemical weathering to create flared slopes and steep-sided inselbergs.
Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis
Authors: Deng Caifeng , Zhang Quan , He Penghui , Zhou Bin , He Ke , Sun Xun , Lei Guanghua , Gong Tao , Zhang Zhirong 
Published: April 2021

AbstractInsufficient apoptosis of inflammatory macrophages and osteoclasts (OCs) in rheumatoid arthritis (RA) joints contributes toward the persistent progression of joint inflammation and destruction. Here, we deliver celastrol (CEL) to selectively induce apoptosis of OCs and macrophages in arthritic joints, with enzyme-responsive nanoparticles (termed PRNPs) composed of RGD modified nanoparticles (termed RNPs) covered with cleavable PEG chains. CEL-loaded PRNPs (CEL-PRNPs) dually target OCs and inflammatory macrophages derived from patients with RA via an RGD-αvβ3 integrin interaction after PEG cleavage by matrix metalloprotease 9, leading to increased apoptosis of these cells. In an adjuvant-induced arthritis rat model, PRNPs have an arthritic joint-specific distribution and CEL-PRNPs efficiently reduce the number of OCs and inflammatory macrophages within these joints. Additionally, rats with advanced arthritis go into inflammatory remission with bone erosion repair and negligible side effects after CEL-PRNPs treatment. These findings indicate potential for targeting chemotherapy-induced apoptosis in the treatment of advanced inflammatory arthritis.
Ultrafast light field tomography for snapshot transient and non-line-of-sight imaging
Authors: Feng Xiaohua , Gao Liang 
Published: April 2021

AbstractCameras with extreme speeds are enabling technologies in both fundamental and applied sciences. However, existing ultrafast cameras are incapable of coping with extended three-dimensional scenes and fall short for non-line-of-sight imaging, which requires a long sequence of time-resolved two-dimensional data. Current non-line-of-sight imagers, therefore, need to perform extensive scanning in the spatial and/or temporal dimension, restricting their use in imaging only static or slowly moving objects. To address these long-standing challenges, we present here ultrafast light field tomography (LIFT), a transient imaging strategy that offers a temporal sequence of over 1000 and enables highly efficient light field acquisition, allowing snapshot acquisition of the complete four-dimensional space and time. With LIFT, we demonstrated three-dimensional imaging of light in flight phenomena with a <10 picoseconds resolution and non-line-of-sight imaging at a 30 Hz video-rate. Furthermore, we showed how LIFT can benefit from deep learning for an improved and accelerated image formation. LIFT may facilitate broad adoption of time-resolved methods in various disciplines.
Autophagy of the m6A mRNA demethylase FTO is impaired by low-level arsenic exposure to promote tumorigenesis
Authors: Cui Yan-Hong , Yang Seungwon , Wei Jiangbo , Shea Christopher R. , Zhong Wen , Wang Fang , Shah Palak , Kibriya Muhammad G. , Cui Xiaolong , Ahsan Habibul , He Chuan , He Yu-Ying 
Published: April 2021

AbstractHere we show that FTO as an N6-methyladenosine (m6A) RNA demethylase is degraded by selective autophagy, which is impaired by low-level arsenic exposure to promote tumorigenesis. We found that in arsenic-associated human skin lesions, FTO is upregulated, while m6A RNA methylation is downregulated. In keratinocytes, chronic relevant low-level arsenic exposure upregulated FTO, downregulated m6A RNA methylation, and induced malignant transformation and tumorigenesis. FTO deletion inhibited arsenic-induced tumorigenesis. Moreover, in mice, epidermis-specific FTO deletion prevented skin tumorigenesis induced by arsenic and UVB irradiation. Targeting FTO genetically or pharmacologically inhibits the tumorigenicity of arsenic-transformed tumor cells. We identified NEDD4L as the m6A-modified gene target of FTO. Finally, arsenic stabilizes FTO protein through inhibiting p62-mediated selective autophagy. FTO upregulation can in turn inhibit autophagy, leading to a positive feedback loop to maintain FTO accumulation. Our study reveals FTO-mediated dysregulation of mRNA m6A methylation as an epitranscriptomic mechanism to promote arsenic tumorigenicity.