bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients
Authors: Qin Shijie , Yao Xiaohong , Li Weiwei , Wang Canbiao , Xu Weijun , Gan Zhenhua , Yang Yang , Zhong Aifang , Wang Bin , He Zhicheng , Wu Jian , Wu Qiuyue , Jiang Weijun , Han Ying , Wang Fan , Wang Zhihua , Ke Yuehua , Zhao Jun , Gao Junyin , Qu Liang , Jin Ping , Guan Miao , Xia Xinyi , Bian Xiuwu 
Published: April 2023

AbstractHow does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell’s activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.
PARP1 mediated PARylation contributes to myogenic progression and glucocorticoid transcriptional response
Authors: Tan Arnold , Younis Awais Z. , Evans Alexander , Creighton Jade V. , Coveny Clare , Boocock David J. , Sale Craig , Lavery Gareth G. , Coutts Amanda S. , Doig Craig L. 
Published: April 2023

AbstractThe ADP-ribosyltransferase, PARP1 enzymatically generates and applies the post-translational modification, ADP-Ribose (ADPR). PARP1 roles in genome maintenance are well described, but recent work highlights roles in many fundamental processes including cellular identity and energy homeostasis. Herein, we show in both mouse and human skeletal muscle cells that PARP1-mediated PARylation is a regulator of the myogenic program and the muscle transcriptional response to steroid hormones. Chemical PARP1 modulation impacts the expression of major myocellular proteins, including troponins, key in dictating muscle contractile force. Whilst PARP1 in absence of DNA damage is often assumed to be basally inactive, we show PARylation to be acutely sensitive to extracellular glucose concentrations and the steroid hormone class, glucocorticoids which exert considerable authority over muscle tissue mass. Specifically, we find during myogenesis, a transient and significant rise in PAR. This early-stage differentiation event, if blocked with PARP1 inhibition, reduced the abundance of important muscle proteins in the fully differentiated myotubes. This suggests that PAR targets during early-stage differentiation are central to the proper development of the muscle contractile unit. We also show that reduced PARP1 in myoblasts impacts a variety of metabolic pathways in line with the recorded actions of glucocorticoids. Currently, as both regulators of myogenesis and muscle mass loss, glucocorticoids represent a clinical conundrum. Our work goes on to identify that PARP1 influences transcriptional activation by glucocorticoids of a subset of genes critical to human skeletal muscle pathology. These genes may therefore signify a regulatory battery of targets through which selective glucocorticoid modulation could be achieved. Collectively, our data provide clear links between PARP1-mediated PARylation and skeletal muscle homeostatic mechanisms crucial to tissue mass maintenance and endocrine response.
Trends and variability in the Southern Annular Mode over the Common Era
Authors: King Jonathan , Anchukaitis Kevin J. , Allen Kathryn , Vance Tessa , Hessl Amy 
Published: April 2023

AbstractThe Southern Annular Mode (SAM) is the leading mode of atmospheric variability in the extratropical Southern Hemisphere and has wide ranging effects on ecosystems and societies. Despite the SAM’s importance, paleoclimate reconstructions disagree on its variability and trends over the Common Era, which may be linked to variability in SAM teleconnections and the influence of specific proxies. Here, we use data assimilation with a multi-model prior to reconstruct the SAM over the last 2000 years using temperature and drought-sensitive climate proxies. Our method does not assume a stationary relationship between the SAM and the proxy records and allows us to identify critical paleoclimate records and quantify reconstruction uncertainty through time. We find no evidence for a forced response in SAM variability prior to the 20th century. We do find the modern positive trend falls outside the 2σrange of the prior 2000 years at multidecadal time scales, supporting the inference that the SAM’s positive trend over the last several decades is a response to anthropogenic climate change.
Unlocking the general relationship between energy and entanglement spectra via the wormhole effect
Authors: Yan Zheng , Meng Zi Yang 
Published: April 2023

AbstractBased on the path integral formulation of the reduced density matrix, we develop a scheme to overcome the exponential growth of computational complexity in reliably extracting low-lying entanglement spectrum from quantum Monte Carlo simulations. We test the method on the Heisenberg spin ladder with long entangled boundary between two chains and the results support the Li and Haldane’s conjecture on entanglement spectrum of topological phase. We then explain the conjecture via the wormhole effect in the path integral and show that it can be further generalized for systems beyond gapped topological phases. Our further simulation results on the bilayer antiferromagnetic Heisenberg model with 2D entangled boundary across the (2 + 1)D O(3) quantum phase transition clearly demonstrate the correctness of the wormhole picture. Finally, we state that since the wormhole effect amplifies the bulk energy gap by a factor of β, the relative strength of that with respect to the edge energy gap will determine the behavior of low-lying entanglement spectrum of the system.
In vivo bioluminescence imaging of natural bacteria within deep tissues via ATP-binding cassette sugar transporter
Authors: Zhang Qian , Song Bin , Xu Yanan , Yang Yunmin , Ji Jian , Cao Wenjun , Lu Jianping , Ding Jiali , Cao Haiting , Chu Binbin , Hong Jiaxu , Wang Houyu , He Yao 
Published: April 2023

AbstractMost existing bioluminescence imaging methods can only visualize the location of engineered bacteria in vivo, generally precluding the imaging of natural bacteria. Herein, we leverage bacteria-specific ATP-binding cassette sugar transporters to internalize luciferase and luciferin by hitchhiking them on the unique carbon source of bacteria. Typically, the synthesized bioluminescent probes are made of glucose polymer (GP), luciferase, Cy5 and ICG-modified silicon nanoparticles and their substrates are made of GP and D-luciferin-modified silicon nanoparticles. Compared with bacteria with mutations in transporters, which hardly internalize the probes in vitro (i.e., ~2% of uptake rate), various bacteria could robustly engulf the probes with a high uptake rate of around 50%. Notably, the developed strategy enables ex vivo bioluminescence imaging of human vitreous containing ten species of pathogens collected from patients with bacterial endophthalmitis. By using this platform, we further differentiate bacterial and non-bacterial nephritis and colitis in mice, while their chemiluminescent counterparts are unable to distinguish them.
Structural basis for botulinum neurotoxin E recognition of synaptic vesicle protein 2
Authors: Liu Zheng , Lee Pyung-Gang , Krez Nadja , Lam Kwok-ho , Liu Hao , Przykopanski Adina , Chen Peng , Yao Guorui , Zhang Sicai , Tremblay Jacqueline M. , Perry Kay , Shoemaker Charles B. , Rummel Andreas , Dong Min , Jin Rongsheng 
Published: April 2023

AbstractBotulinum neurotoxin E (BoNT/E) is one of the major causes of human botulism and paradoxically also a promising therapeutic agent. Here we determined the co-crystal structures of the receptor-binding domain of BoNT/E (HCE) in complex with its neuronal receptor synaptic vesicle glycoprotein 2A (SV2A) and a nanobody that serves as a ganglioside surrogate. These structures reveal that the protein-protein interactions between HCE and SV2 provide the crucial location and specificity information for HCE to recognize SV2A and SV2B, but not the closely related SV2C. At the same time, HCE exploits a separated sialic acid-binding pocket to mediate recognition of an N-glycan of SV2. Structure-based mutagenesis and functional studies demonstrate that both the protein-protein and protein-glycan associations are essential for SV2A-mediated cell entry of BoNT/E and for its potent neurotoxicity. Our studies establish the structural basis to understand the receptor-specificity of BoNT/E and to engineer BoNT/E variants for new clinical applications.
A unifying criterion of the boiling crisis
Authors: Zhang Limiao , Wang Chi , Su Guanyu , Kossolapov Artyom , Matana Aguiar Gustavo , Seong Jee Hyun , Chavagnat Florian , Phillips Bren , Rahman Md Mahamudur , Bucci Matteo 
Published: April 2023

AbstractWe reveal and justify, both theoretically and experimentally, the existence of a unifying criterion of the boiling crisis. This criterion emerges from an instability in the near-wall interactions of bubbles, which can be described as a percolation process driven by three fundamental boiling parameters: nucleation site density, average bubble footprint radius and product of average bubble growth time and detachment frequency. Our analysis suggests that the boiling crisis occurs on a well-defined critical surface in the multidimensional space of these parameters. Our experiments confirm the existence of this unifying criterion for a wide variety of boiling surface geometries and textures, two boiling regimes (pool and flow boiling) and two fluids (water and liquid nitrogen). This criterion constitutes a simple mechanistic rule to predict the boiling crisis, also providing a guiding principle for designing boiling surfaces that would maximize the nucleate boiling performance.
Transcription factor binding site orientation and order are major drivers of gene regulatory activity
Authors: Georgakopoulos-Soares Ilias , Deng Chengyu , Agarwal Vikram , Chan Candace S. Y. , Zhao Jingjing , Inoue Fumitaka , Ahituv Nadav 
Published: April 2023

AbstractThe gene regulatory code and grammar remain largely unknown, precluding our ability to link phenotype to genotype in regulatory sequences. Here, using a massively parallel reporter assay (MPRA) of 209,440 sequences, we examine all possible pair and triplet combinations, permutations and orientations of eighteen liver-associated transcription factor binding sites (TFBS). We find that TFBS orientation and order have a major effect on gene regulatory activity. Corroborating these results with genomic analyses, we find clear human promoter TFBS orientation biases and similar TFBS orientation and order transcriptional effects in an MPRA that tested 164,307 liver candidate regulatory elements. Additionally, by adding TFBS orientation to a model that predicts expression from sequence we improve performance by 7.7%. Collectively, our results show that TFBS orientation and order have a significant effect on gene regulatory activity and need to be considered when analyzing the functional effect of variants on the activity of these sequences.
Nickel/biimidazole-catalyzed electrochemical enantioselective reductive cross-coupling of aryl aziridines with aryl iodides
Authors: Wang Yun-Zhao , Wang Zhen-Hua , Eshel Inbal L. , Sun Bing , Liu Dong , Gu Yu-Cheng , Milo Anat , Mei Tian-Sheng 
Published: April 2023

AbstractHere, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affordingβ-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold.
Para-hydrodynamics from weak surface scattering in ultraclean thin flakes
Authors: Wolf Yotam , Aharon-Steinberg Amit , Yan Binghai , Holder Tobias 
Published: April 2023

AbstractElectron hydrodynamics typically emerges in electron fluids with a high electron–electron collision rate. However, new experiments with thin flakes of WTe2 have revealed that other momentum-conserving scattering processes can replace the role of the electron–electron interaction, thereby leading to a novel, so-called para-hydrodynamic regime. Here, we develop the kinetic theory for para-hydrodynamic transport. To this end, we consider a ballistic electron gas in a thin three-dimensional sheet where the momentum-relaxing (lmr) and momentum-conserving (lmc) mean free paths are decreased due to boundary scattering from a rough surface. The resulting effective mean free path of the in-plane components of the electronic flow is then expressed in terms of microscopic parameters of the sheet boundaries, predicting that a para-hydrodynamic regime with lmr ≫ lmc emerges generically in ultraclean three-dimensional materials. Using our approach, we recover the transport properties of WTe2 in the para-hydrodynamic regime in good agreement with existing experiments.
Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases
Authors: Zelnik Iris D. , Mestre Beatriz , Weinstein Jonathan J. , Dingjan Tamir , Izrailov Stav , Ben-Dor Shifra , Fleishman Sarel J. , Futerman Anthony H. 
Published: April 2023

AbstractUntil now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases.
DNA-binding mechanism and evolution of replication protein A
Authors: Madru Clément , Martínez-Carranza Markel , Laurent Sébastien , Alberti Alessandra C. , Chevreuil Maelenn , Raynal Bertrand , Haouz Ahmed , Le Meur Rémy A. , Delarue Marc , Henneke Ghislaine , Flament Didier , Krupovic Mart , Legrand Pierre , Sauguet Ludovic 
Published: April 2023

AbstractReplication Protein A (RPA) is a heterotrimeric single stranded DNA-binding protein with essential roles in DNA replication, recombination and repair. Little is known about the structure of RPA in Archaea, the third domain of life. By using an integrative structural, biochemical and biophysical approach, we extensively characterize RPA from Pyrococcus abyssi in the presence and absence of DNA. The obtained X-ray and cryo-EM structures reveal that the trimerization core and interactions promoting RPA clustering on ssDNA are shared between archaea and eukaryotes. However, we also identified a helical domain named AROD (Acidic Rpa1 OB-binding Domain), and showed that, in Archaea, RPA forms an unanticipated tetrameric supercomplex in the absence of DNA. The four RPA molecules clustered within the tetramer could efficiently coat and protect stretches of ssDNA created by the advancing replisome. Finally, our results provide insights into the evolution of this primordial replication factor in eukaryotes.
Achieving volatile potassium promoted ammonia synthesis via mechanochemistry
Authors: Kim Jong-Hoon , Dai Tian-Yi , Yang Mihyun , Seo Jeong-Min , Lee Jae Seong , Kweon Do Hyung , Lang Xing-You , Ihm Kyuwook , Shin Tae Joo , Han Gao-Feng , Jiang Qing , Baek Jong-Beom 
Published: April 2023

AbstractPotassium oxide (K2O) is used as a promotor in industrial ammonia synthesis, although metallic potassium (K) is better in theory. The reason K2O is used is because metallic K, which volatilizes around 400 °C, separates from the catalyst in the harsh ammonia synthesis conditions of the Haber-Bosch process. To maximize the efficiency of ammonia synthesis, using metallic K with low temperature reaction below 400 °C is prerequisite. Here, we synthesize ammonia using metallic K and Fe as a catalyst via mechanochemical process near ambient conditions (45 °C, 1 bar). The final ammonia concentration reaches as high as 94.5 vol%, which was extraordinarily higher than that of the Haber-Bosch process (25.0 vol%, 450 °C, 200 bar) and our previous work (82.5 vol%, 45 °C, 1 bar).
High-harmonic generation from a flat liquid-sheet plasma mirror
Authors: Kim Yang Hwan , Kim Hyeon , Park Seong Cheol , Kwon Yongjin , Yeom Kyunghoon , Cho Wosik , Kwon Taeyong , Yun Hyeok , Sung Jae Hee , Lee Seong Ku , Luu Tran Trung , Nam Chang Hee , Kim Kyung Taec 
Published: April 2023

AbstractHigh-harmonic radiation can be generated when an ultra-intense laser beam is reflected from an over-dense plasma, known as a plasma mirror. It is considered a promising technique for generating intense attosecond pulses in the extreme ultraviolet and X-ray wavelength ranges. However, a solid target used for the formation of the over-dense plasma is completely damaged by the interaction. Thus, it is challenging to use a solid target for applications such as time-resolved studies and attosecond streaking experiments that require a large amount of data. Here we demonstrate that high-harmonic radiation can be continuously generated from a liquid plasma mirror in both the coherent wake emission and relativistic oscillating mirror regimes. These results will pave the way for the development of bright, stable, and high-repetition-rate attosecond light sources, which can greatly benefit the study of ultrafast laser-matter interactions.
A massively parallel screening platform for converting aptamers into molecular switches
Authors: Yoshikawa Alex M. , Rangel Alexandra E. , Zheng Liwei , Wan Leighton , Hein Linus A. , Hariri Amani A. , Eisenstein Michael , Soh H. Tom 
Published: April 2023

AbstractAptamer-based molecular switches that undergo a binding-induced conformational change have proven valuable for a wide range of applications, such as imaging metabolites in cells, targeted drug delivery, and real-time detection of biomolecules. Since conventional aptamer selection methods do not typically produce aptamers with inherent structure-switching functionality, the aptamers must be converted to molecular switches in a post-selection process. Efforts to engineer such aptamer switches often use rational design approaches based on in silico secondary structure predictions. Unfortunately, existing software cannot accurately model three-dimensional oligonucleotide structures or non-canonical base-pairing, limiting the ability to identify appropriate sequence elements for targeted modification. Here, we describe a massively parallel screening-based strategy that enables the conversion of virtually any aptamer into a molecular switch without requiring any prior knowledge of aptamer structure. Using this approach, we generate multiple switches from a previously published ATP aptamer as well as a newly-selected boronic acid base-modified aptamer for glucose, which respectively undergo signal-on and signal-off switching upon binding their molecular targets with second-scale kinetics. Notably, our glucose-responsive switch achieves ~30-fold greater sensitivity than a previously-reported natural DNA-based switch. We believe our approach could offer a generalizable strategy for producing target-specific switches from a wide range of aptamers.
Species invasiveness and community invasibility of North American freshwater fish fauna revealed via trait-based analysis
Authors: Su Guohuan , Mertel Adam , Brosse Sébastien , Calabrese Justin M. 
Published: April 2023

AbstractWhile biological invasions are recognized as a major threat to global biodiversity, determining non-native species’ abilities to establish in new areas (species invasiveness) and the vulnerability of those areas to invasions (community invasibility) is challenging. Here, we use trait-based analysis to profile invasive species and quantify the community invasibility for >1,800 North American freshwater fish communities. We show that, in addition to effects attributed to propagule pressure caused by human intervention, species with higher fecundity, longer lifespan and larger size tend to be more invasive. Community invasibility peaks when the functional distance among native species was high, leaving unoccupied functional space for the establishment of potential invaders. Our findings illustrate how the functional traits of non-native species determining their invasiveness, and the functional characteristics of the invaded community determining its invasibility, may be identified. Considering those two determinants together will enable better predictions of invasions.
Modalities of group A streptococcal prevention and treatment and their economic justification
Authors: Cannon Jeffrey W. , Wyber Rosemary 
Published: April 2023

AbstractInfection by group A Streptococcus (Strep A) results in a diverse range of clinical conditions, including pharyngitis, impetigo, cellulitis, necrotising fasciitis, and rheumatic heart disease. In this article, we outline the recommended strategies for Strep A treatment and prevention and review the literature for economic evaluations of competing treatment and prevention strategies. We find that most economic evaluations focus on reducing the duration of illness or risk of rheumatic fever among people presenting with sore throat through diagnostic and/or treatment strategies. Few studies have evaluated strategies to reduce the burden of Strep A infection among the general population, nor have they considered the local capacity to finance and implement strategies. Evaluation of validated costs and consequences for a more diverse range of Strep A interventions are needed to ensure policies maximise patient outcomes under budget constraints. This should include attention to basic public health strategies and emerging strategies such as vaccination.