bluuebunny/crossref_metadata_2025_split huggingface dataset:
A generalized Knudsen theory for gas transport with specular and diffuse reflections
Authors: Qian JianHao , Wu HengAn , Wang FengChao 
Published: November 2023

AbstractGas permeation through nanopores is a long-standing research interest because of its importance in fundamental science and many technologies. The free molecular flow is conventionally described by Knudsen theory, under the diffuse reflection assumption. Recent experiments reported ballistic molecular transport of gases, which urges for the development of theoretical tools to address the predominant specular reflections on atomically smooth surfaces. Here we develop a generalized Knudsen theory, which is applicable to various boundary conditions covering from the extreme specular reflection to the complete diffuse reflection. Our model overcomes the limitation of Smoluchowski model, which predicts the gas flow rate diverging to infinity for specular reflection. It emphasizes that the specular reflection can reduce the dissipation flow rate. Our model is validated using molecular dynamics simulations in various scenarios. The proposed model provides insights into the gas transport under confinement and extends Knudsen theory to free molecular flow with specular reflections.
A cost comparison of various hourly-reliable and net-zero hydrogen production pathways in the United States
Authors: Bracci Justin M. , Sherwin Evan D. , Boness Naomi L. , Brandt Adam R. 
Published: November 2023

AbstractHydrogen (H2) as an energy carrier may play a role in various hard-to-abate subsectors, but to maximize emission reductions, supplied hydrogen must be reliable, low-emission, and low-cost. Here, we build a model that enables direct comparison of the cost of producing net-zero, hourly-reliable hydrogen from various pathways. To reach net-zero targets, we assume upstream and residual facility emissions are mitigated using negative emission technologies. For the United States (California, Texas, and New York), model results indicate next-decade hybrid electricity-based solutions are lower cost ($2.02-$2.88/kg) than fossil-based pathways with natural gas leakage greater than 4% ($2.73-$5.94/kg). These results also apply to regions outside of the U.S. with a similar climate and electric grid. However, when omitting the net-zero emission constraint and considering the U.S. regulatory environment, electricity-based production only achieves cost-competitiveness with fossil-based pathways if embodied emissions of electricity inputs are not counted under U.S. Tax Code Section 45V guidance.
Mercury deposition and redox transformation processes in peatland constrained by mercury stable isotopes
Authors: Li Chuxian , Jiskra Martin , Nilsson Mats B. , Osterwalder Stefan , Zhu Wei , Mauquoy Dmitri , Skyllberg Ulf , Enrico Maxime , Peng Haijun , Song Yu , Björn Erik , Bishop Kevin 
Published: November 2023

AbstractPeatland vegetation takes up mercury (Hg) from the atmosphere, typically contributing to net production and export of neurotoxic methyl-Hg to downstream ecosystems. Chemical reduction processes can slow down methyl-Hg production by releasing Hg from peat back to the atmosphere. The extent of these processes remains, however, unclear. Here we present results from a comprehensive study covering concentrations and isotopic signatures of Hg in an open boreal peatland system to identify post-depositional Hg redox transformation processes. Isotope mass balances suggest photoreduction of HgII is the predominant process by which 30% of annually deposited Hg is emitted back to the atmosphere. Isotopic analyses indicate that above the water table, dark abiotic oxidation decreases peat soil gaseous Hg0 concentrations. Below the water table, supersaturation of gaseous Hg is likely created more by direct photoreduction of rainfall rather than by reduction and release of Hg from the peat soil. Identification and quantification of these light-driven and dark redox processes advance our understanding of the fate of Hg in peatlands, including the potential for mobilization and methylation of HgII.
Single cell transcriptomics shows that malaria promotes unique regulatory responses across multiple immune cell subsets
Authors: Dooley Nicholas L. , Chabikwa Tinashe G. , Pava Zuleima , Loughland Jessica R. , Hamelink Julianne , Berry Kiana , Andrew Dean , Soon Megan S. F. , SheelaNair Arya , Piera Kim A. , William Timothy , Barber Bridget E. , Grigg Matthew J. , Engwerda Christian R. , Lopez J. Alejandro , Anstey Nicholas M. , Boyle Michelle J. 
Published: November 2023

AbstractPlasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.
Polyethyleneimine-coated MXene quantum dots improve cotton tolerance to Verticillium dahliae by maintaining ROS homeostasis
Authors: Qiu Ping , Li Jiayue , Zhang Lin , Chen Kun , Shao Jianmin , Zheng Baoxin , Yuan Hang , Qi Jie , Yue Lin , Hu Qin , Ming Yuqing , Liu Shiming , Long Lu , Gu Jiangjiang , Zhang Xianlong , Lindsey Keith , Gao Wei , Wu Honghong , Zhu Longfu 
Published: November 2023

AbstractVerticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production.
Facile access to benzofuran derivatives through radical reactions with heteroatom-centered super-electron-donors
Authors: Jiang Shichun , Wang Wei , Mou Chengli , Zou Juan , Jin Zhichao , Hao Gefei , Chi Yonggui Robin 
Published: November 2023

AbstractThe development of suitable electron donors is critical to single-electron-transfer (SET) processes. The use of heteroatom-centered anions as super-electron-donors (SEDs) for direct SET reactions has rarely been studied. Here we show that heteroatom anions can be applied as SEDs to initiate radical reactions for facile synthesis of 3-substituted benzofurans. Phosphines, thiols and anilines bearing different substitution patterns work well in this inter-molecular radical coupling reaction and the 3-functionalized benzofuran products bearing heteroatomic functionalities are given in moderate to excellent yields. The reaction mechanism is elucidated via control experiments and computational methods. The afforded products show promising applications in both organic synthesis and pesticide development.
Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch
Authors: Niu Xiaolin , Xu Zhonghe , Zhang Yufan , Zuo Xiaobing , Chen Chunlai , Fang Xianyang 
Published: November 2023

AbstractT-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains unclear. Here, by combining SAXS, single-molecule FRET and computational modeling, we elaborate the folding energy landscape of a translational T-box aptamer consisting of stems I, II and IIA/B, which Mg2+-induced global folding and tRNA binding are cooperatively coupled. smFRET measurements reveal that high Mg2+ stabilizes IIA/B and its stacking on II, which drives the pre-docking of I and II into a competent conformation, subsequent tRNA binding promotes docking of I and II to form a high-affinity tRNA binding groove, of which the essentiality of IIA/B and S-turn in II is substantiated with mutational analysis. We highlight a delicate balance among Mg2+, the intra- and intermolecular RNA-RNA interactions in modulating RNA folding and function.
M. mazei glutamine synthetase and glutamine synthetase-GlnK1 structures reveal enzyme regulation by oligomer modulation
Authors: Schumacher Maria A. , Salinas Raul , Travis Brady A. , Singh Rajiv Ranjan , Lent Nicholas 
Published: November 2023

AbstractGlutamine synthetases (GS) play central roles in cellular nitrogen assimilation. Although GS active-site formation requires the oligomerization of just two GS subunits, all GS form large, multi-oligomeric machines. Here we describe a structural dissection of the archaeal Methanosarcina mazei (Mm) GS and its regulation. We show that Mm GS forms unstable dodecamers. Strikingly, we show this Mm GS oligomerization property is leveraged for a unique mode of regulation whereby labile Mm GS hexamers are stabilized by binding the nitrogen regulatory protein, GlnK1. Our GS-GlnK1 structure shows that GlnK1 functions as molecular glue to affix GS hexamers together, stabilizing formation of GS active-sites. These data, therefore, reveal the structural basis for a unique form of enzyme regulation by oligomer modulation.
Deep learning of human polyadenylation sites at nucleotide resolution reveals molecular determinants of site usage and relevance in disease
Authors: Stroup Emily Kunce , Ji Zhe 
Published: November 2023

AbstractThe genomic distribution of cleavage and polyadenylation (polyA) sites should be co-evolutionally optimized with the local gene structure. Otherwise, spurious polyadenylation can cause premature transcription termination and generate aberrant proteins. To obtain mechanistic insights into polyA site optimization across the human genome, we develop deep/machine learning models to identify genome-wide putative polyA sites at unprecedented nucleotide-level resolution and calculate their strength and usage in the genomic context. Our models quantitatively measure position-specific motif importance and their crosstalk in polyA site formation and cleavage heterogeneity. The intronic site expression is governed by the surrounding splicing landscape. The usage of alternative polyA sites in terminal exons is modulated by their relative locations and distance to downstream genes. Finally, we apply our models to reveal thousands of disease- and trait-associated genetic variants altering polyadenylation activity. Altogether, our models represent a valuable resource to dissect molecular mechanisms mediating genome-wide polyA site expression and characterize their functional roles in human diseases.
Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease
Authors: Gnirck Ann-Christin , Philipp Marie-Sophie , Waterhölter Alex , Wunderlich Malte , Shaikh Nikhat , Adamiak Virginia , Henneken Lena , Kautz Tobias , Xiong Tingting , Klaus Daniela , Tomczyk Pascal , Al-Bahra Mohamad M. , Menche Dirk , Walkenhorst Mark , Lantz Olivier , Willing Anne , Friese Manuel A. , Huber Tobias B. , Krebs Christian F. , Panzer Ulf , Kurts Christian , Turner Jan-Eric 
Published: November 2023

AbstractMucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAITCAST mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-β. Interactome analysis predicts CXCR6 – CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6+ MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.
Pan-genome analysis of 13 Malus accessions reveals structural and sequence variations associated with fruit traits
Authors: Wang Ting , Duan Shiyao , Xu Chen , Wang Yi , Zhang Xinzhong , Xu Xuefeng , Chen Liyang , Han Zhenhai , Wu Ting 
Published: November 2023

AbstractStructural variations (SVs) and copy number variations (CNVs) contribute to trait variations in fleshy-fruited species. Here, we assemble 10 genomes of genetically diverse Malus accessions, including the ever-green cultivar ‘Granny Smith’ and the widely cultivated cultivar ‘Red Fuji’. Combining with three previously reported genomes, we assemble the pan-genome of Malus species and identify 20,220 CNVs and 317,393 SVs. We also observe CNVs that are positively correlated with expression levels of the genes they are associated with. Furthermore, we show that the noncoding RNA generated from a 209 bp insertion in the intron of mitogen-activated protein kinase homology encoding gene, MMK2, regulates the gene expression and affects fruit coloration. Moreover, we identify overlapping SVs associated with fruit quality and biotic resistance. This pan-genome uncovers possible contributions of CNVs to gene expression and highlights the role of SVs in apple domestication and economically important traits.
Impulsive-compulsive behaviour in early Parkinson’s disease is determined by apathy and dopamine receptor D3 polymorphism
Authors: Theis Hendrik , Prange Stéphane , Bischof Gérard N. , Hoenig Merle C. , Tittgemeyer Marc , Timmermann Lars , Fink Gereon R. , Drzezga Alexander , Eggers Carsten , van Eimeren Thilo 
Published: November 2023

AbstractImpulsive-compulsive behaviour (ICB) is a frequently observed non-motor symptom in early Parkinson’s disease after initiating dopamine replacement therapy. At the opposite end of the motivated behaviour spectrum, apathy occurs in early Parkinson’s disease even before dopamine replacement is started. The co-occurrence of these behavioural conditions in Parkinson’s disease raises questions about their relationship and underlying pathophysiological determinants. In previous imaging or genetic studies, both conditions have been associated with the limbic dopaminergic system. The risk variant of the Ser9Gly polymorphism of the dopamine receptor D3 (DRD3) is linked to increased dopamine affinity in the limbic striatum. With this in mind, we investigated how ICB expression is explained by apathy and DRD3 polymorphisms and their effects on grey matter volume and dopamine synthesis capacity. Fifty-four patients with early Parkinson’s disease took part in anatomical T1-weighted MRI. Forty of them also underwent dynamic PET imaging using [18F]DOPA to measure striatal dopamine synthesis capacity. Further, Ser9Gly (rs6280) gene polymorphism influencing the DRD3 dopamine-binding affinity was determined in all patients. The severity of impulsive-compulsive behaviour and apathy was assessed using the Questionnaire for Impulsive-Compulsive Disorders Rating Scale and the Apathy Evaluation Scale. ICB and the severity of apathy were indeed positively correlated. Apathy and the DRD3 polymorphism were interactive risk factors for ICB severity. Apathy was significantly linked to atrophy of the bilateral putamen. Patients with the DRD3 risk type had reduced dopamine synthesis capacity in the putamen and limbic striatum, apathy was associated with reduced dopamine synthesis capacity in the limbic striatum. The results of [18F]DOPA reached only trend significance. Apathy in drug-naïve PD patients might be a consequence of impaired striatal dopaminergic tone. This may represent a predisposing factor for the development of ICB after the initiation of dopamine replacement therapy. The risk type of DRD3 could further amplify this predisposition due to its higher affinity to dopamine.
Single-cell, whole-embryo phenotyping of mammalian developmental disorders
Authors: Huang Xingfan , Henck Jana , Qiu Chengxiang , Sreenivasan Varun K. A. , Balachandran Saranya , Amarie Oana V. , Hrabě de Angelis Martin , Behncke Rose Yinghan , Chan Wing-Lee , Despang Alexandra , Dickel Diane E. , Duran Madeleine , Feuchtinger Annette , Fuchs Helmut , Gailus-Durner Valerie , Haag Natja , Hägerling Rene , Hansmeier Nils , Hennig Friederike , Marshall Cooper , Rajderkar Sudha , Ringel Alessa , Robson Michael , Saunders Lauren M. , da Silva-Buttkus Patricia , Spielmann Nadine , Srivatsan Sanjay R. , Ulferts Sascha , Wittler Lars , Zhu Yiwen , Kalscheuer Vera M. , Ibrahim Daniel M. , Kurth Ingo , Kornak Uwe , Visel Axel , Pennacchio Len A. , Beier David R. , Trapnell Cole , Cao Junyue , Shendure Jay , Spielmann Malte 
Published: November 2023

AbstractMouse models are a critical tool for studying human diseases, particularly developmental disorders1. However, conventional approaches for phenotyping may fail to detect subtle defects throughout the developing mouse2. Here we set out to establish single-cell RNA sequencing of the whole embryo as a scalable platform for the systematic phenotyping of mouse genetic models. We applied combinatorial indexing-based single-cell RNA sequencing3 to profile 101 embryos of 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than 1.6 million nuclei. The 22 mutants represent a range of anticipated phenotypic severities, from established multisystem disorders to deletions of individual regulatory regions4,5. We developed and applied several analytical frameworks for detecting differences in composition and/or gene expression across 52 cell types or trajectories. Some mutants exhibit changes in dozens of trajectories whereas others exhibit changes in only a few cell types. We also identify differences between widely used wild-type strains, compare phenotyping of gain- versus loss-of-function mutants and characterize deletions of topological associating domain boundaries. Notably, some changes are shared among mutants, suggesting that developmental pleiotropy might be ‘decomposable’ through further scaling of this approach. Overall, our findings show how single-cell profiling of whole embryos can enable the systematic molecular and cellular phenotypic characterization of mouse mutants with unprecedented breadth and resolution.
The social and structural architecture of the yeast protein interactome
Authors: Michaelis André C. , Brunner Andreas-David , Zwiebel Maximilian , Meier Florian , Strauss Maximilian T. , Bludau Isabell , Mann Matthias 
Published: November 2023

AbstractCellular functions are mediated by protein–protein interactions, and mapping the interactome provides fundamental insights into biological systems. Affinity purification coupled to mass spectrometry is an ideal tool for such mapping, but it has been difficult to identify low copy number complexes, membrane complexes and complexes that are disrupted by protein tagging. As a result, our current knowledge of the interactome is far from complete, and assessing the reliability of reported interactions is challenging. Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. Thousand-fold reduced volumes in 96-well format enabled replicate analysis of the endogenous GFP-tagged library covering the entire expressed yeast proteome1. The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions, doubling the number of proteins and tripling the number of reliable interactions compared with existing interactome maps2. This includes very-low-abundance epigenetic complexes, organellar membrane complexes and non-taggable complexes inferred by abundance correlation. This nearly saturated interactome reveals that the vast majority of yeast proteins are highly connected, with an average of 16 interactors. Similar to social networks between humans, the average shortest distance between proteins is 4.2 interactions. AlphaFold-Multimer provided novel insights into the functional roles of previously uncharacterized proteins in complexes. Our web portal (www.yeast-interactome.org) enables extensive exploration of the interactome dataset.
A chromosome-level genome assembly of the Knoxia roxburghii (Rubiaceae)
Authors: Zhang Yingmin , Zhang Fan , Jin Ling , Zhang Ticao , Pu Xinying , Qiu Bin , Li Guodong 
Published: November 2023

AbstractKnoxia roxburghii is a well-known medicinal plant that is widely distributed in southern China and Southeast Asia. Its dried roots, known as hongdaji in traditional Chinese medicine, are used to treat a range of diseases, including cancers, carbuncles, and ascites. In this study, we report a de novo chromosome-level genome sequence for this diploid plant, which has a length of approximately 446.30 Mb with a contig N50 size of 42.26 Mb and scaffold N50 size of 44.38 Mb. Approximately 99.78% of the assembled sequences were anchored to 10 pseudochromosomes and 3 gapless assembled chromosomes were included in this assembly. A total of 24,507 genes were annotated, along with 68.92% of repetitive elements. Overall, our results will facilitate further active component biosynthesis for K. roxburghii and provide insights for future functional genomic studies and DNA-informed breeding.