bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell fate determining molecular switches and signaling pathways in Pax7-expressing somitic mesoderm
Authors: Fung Cheuk Wang , Zhou Shaopu , Zhu Han , Wei Xiuqing , Wu Zhenguo , Wu Angela Ruohao 
Published: June 2022

AbstractDuring development, different cell types originate from a common progenitor at well-defined time points. Previous lineage-tracing of Pax7+ progenitors from the somitic mesoderm has established its developmental trajectory towards the dermis, brown adipocytes, and skeletal muscle in the dorsal trunk; yet the molecular switches and mechanisms guiding the differentiation into different lineages remain unknown. We performed lineage-tracing of Pax7-expressing cells in mouse embryos at E9.5 and profiled the transcriptomes of Pax7-progenies on E12.5, E14.5, and E16.5 at single-cell level. Analysis of single-cell transcriptomic data at multiple time points showed temporal-specific differentiation events toward muscle, dermis, and brown adipocyte, identified marker genes for putative progenitors and revealed transcription factors that could drive lineage-specific differentiation. We then utilized a combination of surface markers identified in the single-cell data, Pdgfra, Thy1, and Cd36, to enrich brown adipocytes, dermal fibroblasts, and progenitors specific for these two cell types at E14.5 and E16.5. These enriched cell populations were then used for further culture and functional assays in vitro, in which Wnt5a and Rgcc are shown to be important factors that could alter lineage decisions during embryogenesis. Notably, we found a bipotent progenitor population at E14.5, having lineage potentials towards both dermal fibroblasts and brown adipocytes. They were termed eFAPs (embryonic fibro/adipogenic progenitors) as they functionally resemble adult fibro/adipogenic progenitors. Overall, this study provides further understanding of the Pax7 lineage during embryonic development using a combination of lineage tracing with temporally sampled single-cell transcriptomics.
Phase separation of insulin receptor substrate 1 drives the formation of insulin/IGF-1 signalosomes
Authors: Gao Xiu Kui , Rao Xi Sheng , Cong Xiao Xia , Sheng Zu Kang , Sun Yu Ting , Xu Shui Bo , Wang Jian Feng , Liang Yong Heng , Lu Lin Rong , Ouyang Hongwei , Ge Huiqing , Guo Jian-sheng , Wu Hang-jun , Sun Qi Ming , Wu Hao-bo , Bao Zhang , Zheng Li Ling , Zhou Yi Ting 
Published: June 2022

AbstractAs a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301–600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.
The timing of unprecedented hydrological drought under climate change
Authors: Satoh Yusuke , Yoshimura Kei , Pokhrel Yadu , Kim Hyungjun , Shiogama Hideo , Yokohata Tokuta , Hanasaki Naota , Wada Yoshihide , Burek Peter , Byers Edward , Schmied Hannes Müller , Gerten Dieter , Ostberg Sebastian , Gosling Simon Newland , Boulange Julien Eric Stanslas , Oki Taikan 
Published: June 2022

AbstractDroughts that exceed the magnitudes of historical variation ranges could occur increasingly frequently under future climate conditions. However, the time of the emergence of unprecedented drought conditions under climate change has rarely been examined. Here, using multimodel hydrological simulations, we investigate the changes in the frequency of hydrological drought (defined as abnormally low river discharge) under high and low greenhouse gas concentration scenarios and existing water resource management measures and estimate the time of the first emergence of unprecedented regional drought conditions centered on the low-flow season. The times are detected for several subcontinental-scale regions, and three regions, namely, Southwestern South America, Mediterranean Europe, and Northern Africa, exhibit particularly robust results under the high-emission scenario. These three regions are expected to confront unprecedented conditions within the next 30 years with a high likelihood regardless of the emission scenarios. In addition, the results obtained herein demonstrate the benefits of the lower-emission pathway in reducing the likelihood of emergence. The Paris Agreement goals are shown to be effective in reducing the likelihood to the unlikely level in most regions. However, appropriate and prior adaptation measures are considered indispensable when facing unprecedented drought conditions. The results of this study underscore the importance of improving drought preparedness within the considered time horizons.
Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records
Authors: Thompson Ellen J. , Williams Dylan M. , Walker Alex J. , Mitchell Ruth E. , Niedzwiedz Claire L. , Yang Tiffany C. , Huggins Charlotte F. , Kwong Alex S. F. , Silverwood Richard J. , Di Gessa Giorgio , Bowyer Ruth C. E. , Northstone Kate , Hou Bo , Green Michael J. , Dodgeon Brian , Doores Katie J. , Duncan Emma L. , Williams Frances M. K. ,   OpenSAFELY Collaborative, Walker Alex J. , MacKenna Brian , Inglesby Peter , Rentsch Christopher T. , Curtis Helen J. , Morton Caroline E. , Morley Jessica , Mehrkar Amir , Bacon Seb , Hickman George , Bates Chris , Croker Richard , Evans David , Ward Tom , Cockburn Jonathan , Davy Simon , Bhaskaran Krishnan , Schultze Anna , Williamson Elizabeth J. , Hulme William J. , McDonald Helen I. , Tomlinson Laurie , Mathur Rohini , Eggo Rosalind M. , Wing Kevin , Wong Angel Y. S. , Forbes Harriet , Tazare John , Parry John , Hester Frank , Harper Sam , Douglas Ian J. , Evans Stephen J. W. , Smeeth Liam , Goldacre Ben , Steptoe Andrew , Porteous David J. , McEachan Rosemary R. C. , Tomlinson Laurie , Goldacre Ben , Patalay Praveetha , Ploubidis George B. , Katikireddi Srinivasa Vittal , Tilling Kate , Rentsch Christopher T. , Timpson Nicholas J. , Chaturvedi Nishi , Steves Claire J. 
Published: June 2022

AbstractThe frequency of, and risk factors for, long COVID are unclear among community-based individuals with a history of COVID-19. To elucidate the burden and possible causes of long COVID in the community, we coordinated analyses of survey data from 6907 individuals with self-reported COVID-19 from 10 UK longitudinal study (LS) samples and 1.1 million individuals with COVID-19 diagnostic codes in electronic healthcare records (EHR) collected by spring 2021. Proportions of presumed COVID-19 cases in LS reporting any symptoms for 12+ weeks ranged from 7.8% and 17% (with 1.2 to 4.8% reporting debilitating symptoms). Increasing age, female sex, white ethnicity, poor pre-pandemic general and mental health, overweight/obesity, and asthma were associated with prolonged symptoms in both LS and EHR data, but findings for other factors, such as cardio-metabolic parameters, were inconclusive.
Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms
Authors: Atyeo Caroline G. , Shook Lydia L. , Brigida Sara , De Guzman Rose M. , Demidkin Stepan , Muir Cordelia , Akinwunmi Babatunde , Baez Arantxa Medina , Sheehan Maegan L. , McSweeney Erin , Burns Madeleine D. , Nayak Ruhi , Kumar Maya K. , Patel Chinmay D. , Fialkowski Allison , Cvrk Dana , Goldfarb Ilona T. , Yonker Lael M. , Fasano Alessio , Balazs Alejandro B. , Elovitz Michal A. , Gray Kathryn J. , Alter Galit , Edlow Andrea G. 
Published: June 2022

AbstractThe availability of three COVID-19 vaccines in the United States provides an unprecedented opportunity to examine how vaccine platforms and timing of vaccination in pregnancy impact maternal and neonatal immunity. Here, we characterize the antibody profile after Ad26.COV2.S, mRNA-1273 or BNT162b2 vaccination in 158 pregnant individuals and evaluate transplacental antibody transfer by profiling maternal and umbilical cord blood in 175 maternal-neonatal dyads. These analyses reveal lower vaccine-induced functions and Fc receptor-binding after Ad26.COV2.S compared to mRNA vaccination and subtle advantages in titer and function with mRNA-1273 versus BN162b2. mRNA vaccines have higher titers and functions against SARS-CoV-2 variants of concern. First and third trimester vaccination results in enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition relative to second trimester. Higher transplacental transfer ratios following first and second trimester vaccination may reflect placental compensation for waning maternal titers. These results provide novel insight into the impact of platform and trimester of vaccination on maternal humoral immune response and transplacental antibody transfer.
Senescent cells limit p53 activity via multiple mechanisms to remain viable
Authors: Sturmlechner Ines , Sine Chance C. , Jeganathan Karthik B. , Zhang Cheng , Fierro Velasco Raul O. , Baker Darren J. , Li Hu , van Deursen Jan M. 
Published: June 2022

AbstractSuper-enhancers regulate genes with important functions in processes that are cell type-specific or define cell identity. Mouse embryonic fibroblasts establish 40 senescence-associated super-enhancers regardless of how they become senescent, with 50 activated genes located in the vicinity of these enhancers. Here we show, through gene knockdown and analysis of three core biological properties of senescent cells that a relatively large number of senescence-associated super-enhancer-regulated genes promote survival of senescent mouse embryonic fibroblasts. Of these, Mdm2, Rnase4, and Ang act by suppressing p53-mediated apoptosis through various mechanisms that are also engaged in response to DNA damage. MDM2 and RNASE4 transcription is also elevated in human senescent fibroblasts to restrain p53 and promote survival. These insights identify key survival mechanisms of senescent cells and provide molecular entry points for the development of targeted therapeutics that eliminate senescent cells at sites of pathology.
Lsm7 phase-separated condensates trigger stress granule formation
Authors: Lindström Michelle , Chen Lihua , Jiang Shan , Zhang Dan , Gao Yuan , Zheng Ju , Hao Xinxin , Yang Xiaoxue , Kabbinale Arpitha , Thoma Johannes , Metzger Lisa C. , Zhang Deyuan Y. , Zhu Xuefeng , Liu Huisheng , Gustafsson Claes M. , Burmann Björn M. , Winderickx Joris , Sunnerhagen Per , Liu Beidong 
Published: June 2022

AbstractStress granules (SGs) are non-membranous organelles facilitating stress responses and linking the pathology of age-related diseases. In a genome-wide imaging-based phenomic screen, we identify Pab1 co-localizing proteins under 2-deoxy-D-glucose (2-DG) induced stress in Saccharomyces cerevisiae. We find that deletion of one of the Pab1 co-localizing proteins, Lsm7, leads to a significant decrease in SG formation. Under 2-DG stress, Lsm7 rapidly forms foci that assist in SG formation. The Lsm7 foci form via liquid-liquid phase separation, and the intrinsically disordered region and the hydrophobic clusters within the Lsm7 sequence are the internal driving forces in promoting Lsm7 phase separation. The dynamic Lsm7 phase-separated condensates appear to work as seeding scaffolds, promoting Pab1 demixing and subsequent SG initiation, seemingly mediated by RNA interactions. The SG initiation mechanism, via Lsm7 phase separation, identified in this work provides valuable clues for understanding the mechanisms underlying SG formation and SG-associated human diseases.
Compositional dependence of the fragility in metallic glass forming liquids
Authors: Kube Sebastian A. , Sohn Sungwoo , Ojeda-Mota Rodrigo , Evers Theo , Polsky William , Liu Naijia , Ryan Kevin , Rinehart Sean , Sun Yong , Schroers Jan 
Published: June 2022

AbstractThe viscosity and its temperature dependence, the fragility, are key properties of a liquid. A low fragility is believed to promote the formation of metallic glasses. Yet, the fragility remains poorly understood, since experimental data of its compositional dependence are scarce. Here, we introduce the film inflation method (FIM), which measures the fragility of metallic glass forming liquids across wide ranges of composition and glass-forming ability. We determine the fragility for 170 alloys ranging over 25 at.% in Mg–Cu–Y. Within this alloy system, large fragility variations are observed. Contrary to the general understanding, a low fragility does not correlate with high glass-forming ability here. We introduce crystallization complexity as an additional contribution, which can potentially become significant when modeling glass forming ability over many orders of magnitude.
Immunogenicity and reactogenicity of SARS-CoV-2 vaccines BNT162b2 and CoronaVac in healthy adolescents
Authors: Rosa Duque Jaime S. , Wang Xiwei , Leung Daniel , Cheng Samuel M. S. , Cohen Carolyn A. , Mu Xiaofeng , Hachim Asmaa , Zhang Yanmei , Chan Sau Man , Chaothai Sara , Kwan Kelvin K. H. , Chan Karl C. K. , Li John K. C. , Luk Leo L. H. , Tsang Leo C. H. , Wong Wilfred H. S. , Cheang Cheuk Hei , Hung Timothy K. , Lam Jennifer H. Y. , Chua Gilbert T. , Tso Winnie W. Y. , Ip Patrick , Mori Masashi , Kavian Niloufar , Leung Wing Hang , Valkenburg Sophie , Peiris Malik , Tu Wenwei , Lau Yu Lung 
Published: June 2022

AbstractWe present an interim analysis of a registered clinical study (NCT04800133) to establish immunobridging with various antibody and cellular immunity markers and to compare the immunogenicity and reactogenicity of 2-dose BNT162b2 and CoronaVac in healthy adolescents as primary objectives. One-dose BNT162b2, recommended in some localities for risk reduction of myocarditis, is also assessed. Antibodies and T cell immune responses are non-inferior or similar in adolescents receiving 2 doses of BNT162b2 (BB,N = 116) and CoronaVac (CC,N = 123) versus adults after 2 doses of the same vaccine (BB,N = 147; CC,N = 141) but not in adolescents after 1-dose BNT162b2 (B,N = 116). CC induces SARS-CoV-2 N and N C-terminal domain seropositivity in a higher proportion of adolescents than adults. Adverse reactions are mostly mild for both vaccines and more frequent for BNT162b2. We find higher S, neutralising, avidity and Fc receptor-binding antibody responses in adolescents receiving BB than CC, and a similar induction of strong S-specific T cells by the 2 vaccines, in addition to N- and M-specific T cells induced by CoronaVac but not BNT162b2, possibly implying differential durability and cross-variant protection by BNT162b2 and CoronaVac, the 2 most used SARS-CoV-2 vaccines worldwide. Our results support the use of both vaccines in adolescents.
Network-based machine learning approach to predict immunotherapy response in cancer patients
Authors: Kong JungHo , Ha Doyeon , Lee Juhun , Kim Inhae , Park Minhyuk , Im Sin-Hyeog , Shin Kunyoo , Kim Sanguk 
Published: June 2022

AbstractImmune checkpoint inhibitors (ICIs) have substantially improved the survival of cancer patients over the past several years. However, only a minority of patients respond to ICI treatment (~30% in solid tumors), and current ICI-response-associated biomarkers often fail to predict the ICI treatment response. Here, we present a machine learning (ML) framework that leverages network-based analyses to identify ICI treatment biomarkers (NetBio) that can make robust predictions. We curate more than 700 ICI-treated patient samples with clinical outcomes and transcriptomic data, and observe that NetBio-based predictions accurately predict ICI treatment responses in three different cancer types—melanoma, gastric cancer, and bladder cancer. Moreover, the NetBio-based prediction is superior to predictions based on other conventional ICI treatment biomarkers, such as ICI targets or tumor microenvironment-associated markers. This work presents a network-based method to effectively select immunotherapy-response-associated biomarkers that can make robust ML-based predictions for precision oncology.
Anionic polymerization of nonaromatic maleimide to achieve full-color nonconventional luminescence
Authors: Ji Xin , Tian Weiguo , Jin Kunfeng , Diao Huailing , Huang Xin , Song Guangjie , Zhang Jun 
Published: June 2022

AbstractNonconventional or nonconjugated luminophore without polycyclic aromatics or extended π-conjugation is a rising star in the area of luminescent materials. However, continuously tuning the emission color within a broad visible region via rational molecular design remains quite challenging because the mechanism of nonconventional luminescence is not fully understood. Herein, we present a new class of nonconventional luminophores, poly(maleimide)s (PMs), with full-color emission that can be finely regulated by anionic polymerization even at ambient temperature. Interestingly, the general characteristics of nonconventional luminescence, cluster-triggered emission, e.g., concentration-enhanced emission, are not observed in PMs. Instead, PMs have features similar to aggregation-caused quenching due to boosted intra/inter-molecular charge transfer. Such a biocompatible luminescent material synthesized from a low-cost monomer shows great prospects in large-scale production and applications, including security printing, fingerprint identification, metal ion recognition, etc. It also provides a new platform of rational molecular design to achieve full-color nonconventional luminescence without any aromatics.
Machine learning for the discovery of molecular recognition based on single-walled carbon nanotube corona-phases
Authors: Gong Xun , Renegar Nicholas , Levi Retsef , Strano Michael S. 
Published: June 2022

AbstractNanoparticle corona phase (CP) design offers a unique approach toward molecular recognition (MR) for sensing applications. Single-walled carbon nanotube (SWCNT) CPs can additionally transduce MR through its band-gap photoluminescence (PL). While DNA oligonucleotides have been used as SWCNT CPs, no generalized scheme exists for MR prediction de novo due to their sequence-dependent three-dimensional complexity. This work generated the largest DNA-SWCNT PL response library of 1408 elements and leveraged machine learning (ML) techniques to understand MR and DNA sequence dependence through local (LFs) and high-level features (HLFs). Out-of-sample analysis of our ML model showed significant correlations between model predictions and actual sensor responses for 6 out of 8 experimental conditions. Different HLF combinations were found to be uniquely correlated with different analytes. Furthermore, models utilizing both LFs and HLFs show improvement over that with HLFs alone, demonstrating that DNA-SWCNT CP engineering is more complex than simply specifying molecular properties.
A high-resolution climate simulation dataset for the past 540 million years
Authors: Li Xiang , Hu Yongyun , Guo Jiaqi , Lan Jiawenjing , Lin Qifan , Bao Xiujuan , Yuan Shuai , Wei Mengyu , Li Zhibo , Man Kai , Yin Zihan , Han Jing , Zhang Jian , Zhu Chenguang , Zhao Zhouqiao , Liu Yonggang , Yang Jun , Nie Ji 
Published: June 2022

AbstractThe Phanerozoic Eon has witnessed considerable changes in the climate system as well as abundant animals and plant life. Therefore, the evolution of the climate system in this Eon is worthy of extensive research. Only by studying climate changes in the past can we understand the driving mechanisms for climate changes in the future and make reliable climate projections. Apart from observational paleoclimate proxy datasets, climate simulations provide an alternative approach to investigate past climate conditions of the Earth, especially for long time span in the deep past. Here we perform 55 snapshot simulations for the past 540 million years, with a 10-million-year interval, using the Community Earth System Model version 1.2.2 (CESM1.2.2). The climate simulation dataset includes global distributions of monthly surface temperatures and precipitation, with a 1° horizontal resolution of 0.9° × 1.25° in latitude and longitude. This open access climate dataset is useful for multidisciplinary research, such as paleoclimate, geology, geochemistry, and paleontology.
Equivocal evidence for a link between megalencephaly-related genes and primate brain size evolution
Authors: DeCasien Alex R. , Trujillo Amber E. , Janiak Mareike C. , Harshaw Etta P. , Caes Zosia N. , Galindo Gabriela A. , Petersen Rachel M. , Higham James P. 
Published: June 2022

AbstractA large brain is a defining feature of modern humans, and much work has been dedicated to exploring the molecular underpinnings of this trait. Although numerous studies have focused on genes associated with human microcephaly, no studies have explicitly focused on genes associated with megalencephaly. Here, we investigate 16 candidate genes that have been linked to megalencephaly to determine if: (1) megalencephaly-associated genes evolved under positive selection across primates; and (2) selection pressure on megalencephaly-associated genes is linked to primate brain size. We found evidence for positive selection for only one gene,OFD1, with 1.8% of the sites estimated to have dN/dSvalues greater than 1; however, we did not detect a relationship between selection pressure on this gene and brain size across species, suggesting that selection for changes to non-brain size traits drove evolutionary changes to this gene. In fact, our primary analyses did not identify significant associations between selection pressure and brain size for any candidate genes. While we did detect positive associations for two genes (GPC3andTBC1D7) when two phyletic dwarfs (i.e., species that underwent recent evolutionary decreases in brain size) were excluded, these associations did not withstand FDR correction. Overall, these results suggest that sequence alterations to megalencephaly-associated genes may have played little to no role in primate brain size evolution, possibly due to the highly pleiotropic effects of these genes. Future comparative studies of gene expression levels may provide further insights. This study enhances our understanding of the genetic underpinnings of brain size evolution in primates and identifies candidate genes that merit further exploration.