bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of the plant hormone gibberellin by rhizobia increases host legume nodule size
Authors: Nett Ryan S , Bender Kelly S , Peters Reuben J 
Published: April 2022

Abstract
Plant-associated microbes have evolved the ability to independently produce gibberellin (GA) phytohormones as a mechanism to influence their host. Indeed, GA was first discovered as a metabolite from the fungal rice pathogen Gibberella fujikuroi, which uses it as a virulence factor. Though some bacterial plant pathogens similarly use GA to promote infection, symbiotic nitrogen-fixing bacteria (rhizobia), which inhabit the root nodules of legumes, also can produce GA, suggesting a role in symbiosis. The bacterial GA biosynthetic operon has been identified, but in rhizobia this typically no longer encodes the final metabolic gene (cyp115), so that these symbionts can only produce the penultimate intermediate GA9. Here, we demonstrate that soybean (Glycine max) expresses functional GA 3-oxidases (GA3ox) within its nodules, which have the capability to convert GA9 produced by the enclosed rhizobial symbiont Bradyrhizobium diazoefficiens to bioactive GA4. This rhizobia-derived GA is demonstrated to cause an increase in nodule size and decrease in the number of nodules. The increase in individual nodule size correlates to greater numbers of bacterial progeny within a nodule, thereby providing a selective advantage to rhizobia that produce GA during the rhizobia-legume symbiosis. The expression of GA3ox in nodules and resultant nodulation effects of the GA product suggests that soybean has co-opted control of bioactive GA production, and thus nodule size, for its own benefit. Thus, our results suggest rhizobial GA biosynthesis has coevolved with host plant metabolism for cooperative production of a phytohormone that influences nodulation in a mutually beneficial manner.
A positive feedback loop: RAD18-YAP-TGF-β between triple-negative breast cancer and macrophages regulates cancer stemness and progression
Authors: Yan Xueqi , He Yaozhou , Yang Shikun , Zeng Tianyu , Hua Yijia , Bao Shengnan , Yang Fan , Duan Ningjun , Sun Chunxiao , Liang Yan , Fu Ziyi , Huang Xiang , Li Wei , Yin Yongmei 
Published: April 2022

AbstractAs a key regulator of the DNA translesion synthesis (TLS) pathway, RAD18 is error-prone and contributes to the accumulation of DNA mutations. Our previous study showed that it plays an essential role in the progression of multiple tumors. However, the mechanism through which RAD18 influences triple-negative breast cancer (TNBC), especially the interaction between tumor cells and the tumor microenvironment, remains elusive. In this study, we showed that RAD18 expression is markedly higher in patients with high T stage TNBC and inversely correlated with prognosis. High expression of RAD18 facilitated a highly stem-cell phenotype through the Hippo/YAP pathway, which supports the proliferation of TNBC. In addition, the cytokine byproduct TGF-β activates macrophages to have an M2-like tumor-associated macrophage (TAM) phenotype. Reciprocally, TGF-β from TAMs activated RAD18 in TNBC to enhance tumor stemness, forming a positive feedback loop. Inhibition of YAP or TGF-β breaks this loop and suppresses cancer stemness and proliferation In nude mice, RAD18 promoted subcutaneous transplanted tumor growth and M2-type TAM recruitment. Collectively, the RAD18-YAP-TGF-β loop is essential for the promotion of the stemness phenotype by TNBC and could be a potential therapeutic target for TNBC.
A machine learning algorithm with subclonal sensitivity reveals widespread pan-cancer human leukocyte antigen loss of heterozygosity
Authors: Pyke Rachel Marty , Mellacheruvu Dattatreya , Dea Steven , Abbott Charles W. , McDaniel Lee , Bhave Devayani P. , Zhang Simo V. , Levy Eric , Bartha Gabor , West John , Snyder Michael P. , Chen Richard O. , Boyle Sean Michael 
Published: April 2022

AbstractHuman leukocyte antigen loss of heterozygosity (HLA LOH) allows cancer cells to escape immune recognition by deleting HLA alleles, causing the suppressed presentation of tumor neoantigens. Despite its importance in immunotherapy response, few methods exist to detect HLA LOH, and their accuracy is not well understood. Here, we develop DASH (Deletion of Allele-Specific HLAs), a machine learning-based algorithm to detect HLA LOH from paired tumor-normal sequencing data. With cell line mixtures, we demonstrate increased sensitivity compared to previously published tools. Moreover, our patient-specific digital PCR validation approach provides a sensitive, robust orthogonal approach that could be used for clinical validation. Using DASH on 610 patients across 15 tumor types, we find that 18% of patients have HLA LOH. Moreover, we show inflated HLA LOH rates compared to genome-wide LOH and correlations between CD274 (encodes PD-L1) expression and microsatellite instability status, suggesting the HLA LOH is a key immune resistance strategy.
ComFC mediates transport and handling of single-stranded DNA during natural transformation
Authors: Damke Prashant P. , Celma Louisa , Kondekar Sumedha M. , Di Guilmi Anne Marie , Marsin Stéphanie , Dépagne Jordane , Veaute Xavier , Legrand Pierre , Walbott Hélène , Vercruyssen Julien , Guérois Raphaël , Quevillon-Cheruel Sophie , Radicella J. Pablo 
Published: April 2022

AbstractThe ComFC protein is essential for natural transformation, a process that plays a major role in the spread of antibiotic resistance genes and virulence factors across bacteria. However, its role remains largely unknown. Here, we show that Helicobacter pylori ComFC is involved in DNA transport through the cell membrane, and is required for the handling of the single-stranded DNA once it is delivered into the cytoplasm. The crystal structure of ComFC includes a zinc-finger motif and a putative phosphoribosyl transferase domain, both necessary for the protein’s in vivo activity. Furthermore, we show that ComFC is a membrane-associated protein with affinity for single-stranded DNA. Our results suggest that ComFC provides the link between the transport of the transforming DNA into the cytoplasm and its handling by the recombination machinery.
Persistent COVID-19 symptoms in a community study of 606,434 people in England
Authors: Whitaker Matthew , Elliott Joshua , Chadeau-Hyam Marc , Riley Steven , Darzi Ara , Cooke Graham , Ward Helen , Elliott Paul 
Published: April 2022

AbstractLong COVID remains a broadly defined syndrome, with estimates of prevalence and duration varying widely. We use data from rounds 3–5 of the REACT-2 study (n = 508,707; September 2020 – February 2021), a representative community survey of adults in England, and replication data from round 6 (n = 97,717; May 2021) to estimate the prevalence and identify predictors of persistent symptoms lasting 12 weeks or more; and unsupervised learning to cluster individuals by reported symptoms. At 12 weeks in rounds 3–5, 37.7% experienced at least one symptom, falling to 21.6% in round 6. Female sex, increasing age, obesity, smoking, vaping, hospitalisation with COVID-19, deprivation, and being a healthcare worker are associated with higher probability of persistent symptoms in rounds 3–5, and Asian ethnicity with lower probability. Clustering analysis identifies a subset of participants with predominantly respiratory symptoms. Managing the long-term sequelae of COVID-19 will remain a major challenge for affected individuals and their families and for health services.
Using high-resolution contact networks to evaluate SARS-CoV-2 transmission and control in large-scale multi-day events
Authors: Pung Rachael , Firth Josh A. , Spurgin Lewis G. ,   Singapore CruiseSafe working group, Chang Annie , Kong Jade , Wong Jazzy , Jin Ooi Jo , Selvaraj Deepa , Yong Dominique , Lang Jocelyn , Sivalingam Abilash ,   CMMID COVID-19 working group, Procter Simon R. , Flasche Stefan , Waites William , Prem Kiesha , Pearson Carl A. B. , Gibbs Hamish P. , Sherratt Katharine , Villabona-Arenas C. Julian , Wong Kerry L. M. , Liu Yang , Mee Paul , Chapman Lloyd A. C. , Atkins Katherine E. , Quaife Matthew , Munday James D. , Funk Sebastian , Eggo Rosalind M. , Huè Stèphane , Davies Nicholas G. , Hodgson David , Abbas Kaja , McCarthy Ciara V. , Hellewell Joel , Abbott Sam , Bosse Nikos I. , Brady Oliver , Barnard Rosanna C. , Jit Mark , Tully Damien C. , Medley Graham , Sun Fiona Yueqian , Jarvis Christopher I. , Lowev Rachel , O’Reilly Kathleen , Meakin Sophie R. , Endo Akira , Sandmann Frank G. , Edmunds W. John , Koltai Mihaly , Finch Emilie , Gimma Amy , Rosello Alicia , Quilty Billy J. , Jafari Yalda , Knight Gwenan M. , Clifford Samuel , Russell Timothy W. , Lee Vernon J. , Kucharski Adam J. 
Published: April 2022

AbstractThe emergence of highly transmissible SARS-CoV-2 variants has created a need to reassess the risk posed by increasing social contacts as countries resume pre-pandemic activities, particularly in the context of resuming large-scale events over multiple days. To examine how social contacts formed in different activity settings influences interventions required to control Delta variant outbreaks, we collected high-resolution data on contacts among passengers and crew on cruise ships and combined the data with network transmission models. We found passengers had a median of 20 (IQR 10–36) unique close contacts per day, and over 60% of their contact episodes were made in dining or sports areas where mask wearing is typically limited. In simulated outbreaks, we found that vaccination coverage and rapid antigen tests had a larger effect than mask mandates alone, indicating the importance of combined interventions against Delta to reduce event risk in the vaccine era.
Therapeutic homology-independent targeted integration in retina and liver
Authors: Tornabene Patrizia , Ferla Rita , Llado-Santaeularia Manel , Centrulo Miriam , Dell’Anno Margherita , Esposito Federica , Marrocco Elena , Pone Emanuela , Minopoli Renato , Iodice Carolina , Nusco Edoardo , Rossi Settimio , Lyubenova Hristiana , Manfredi Anna , Di Filippo Lucio , Iuliano Antonella , Torella Annalaura , Piluso Giulio , Musacchia Francesco , Surace Enrico Maria , Cacchiarelli Davide , Nigro Vincenzo , Auricchio Alberto 
Published: April 2022

AbstractChallenges to the widespread application of gene therapy with adeno-associated viral (AAV) vectors include dominant conditions due to gain-of-function mutations which require allele-specific knockout, as well as long-term transgene expression from proliferating tissues, which is hampered by AAV DNA episomal status. To overcome these challenges, we used CRISPR/Cas9-mediated homology-independent targeted integration (HITI) in retina and liver as paradigmatic target tissues. We show that AAV-HITI targets photoreceptors of both mouse and pig retina, and this results in significant improvements to retinal morphology and function in mice with autosomal dominant retinitis pigmentosa. In addition, we show that neonatal systemic AAV-HITI delivery achieves stable liver transgene expression and phenotypic improvement in a mouse model of a severe lysosomal storage disease. We also show that HITI applications predominantly result in on-target editing. These results lay the groundwork for the application of AAV-HITI for the treatment of diseases affecting various organs.
The crystal structure of iC3b-CR3 αI reveals a modular recognition of the main opsonin iC3b by the CR3 integrin receptor
Authors: Fernández Francisco J. , Santos-López Jorge , Martínez-Barricarte Rubén , Querol-García Javier , Martín-Merinero Héctor , Navas-Yuste Sergio , Savko Martin , Shepard William E. , Rodríguez de Córdoba Santiago , Vega M. Cristina 
Published: April 2022

AbstractComplement activation on cell surfaces leads to the massive deposition of C3b, iC3b, and C3dg, the main complement opsonins. Recognition of iC3b by complement receptor type 3 (CR3) fosters pathogen opsonophagocytosis by macrophages and the stimulation of adaptive immunity by complement-opsonized antigens. Here, we present the crystallographic structure of the complex between human iC3b and the von Willebrand A inserted domain of the α chain of CR3 (αI). The crystal contains two composite interfaces for CR3 αI, encompassing distinct sets of contiguous macroglobulin (MG) domains on the C3c moiety, MG1-MG2 and MG6-MG7 domains. These composite binding sites define two iC3b-CR3 αI complexes characterized by specific rearrangements of the two semi-independent modules, C3c moiety and TED domain. Furthermore, we show the structure of iC3b in a physiologically-relevant extended conformation. Based on previously available data and novel insights reported herein, we propose an integrative model that reconciles conflicting facts about iC3b structure and function and explains the molecular basis for iC3b selective recognition by CR3 on opsonized surfaces.
SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes
Authors: Nikolov Vladislav N. , Malavia Dhara , Kubota Takashi 
Published: April 2022

AbstractThe Pleiotropic Drug Resistance (PDR) network is central to the drug response in fungi, and its overactivation is associated with drug resistance. However, gene regulation of the PDR network is not well understood. Here, we show that the histone chaperone Rtt106 and the chromatin remodeller SWI/SNF control expression of the PDR network genes and confer drug resistance. In Saccharomyces cerevisiae, Rtt106 specifically localises to PDR network gene promoters dependent on transcription factor Pdr3, but not Pdr1, and is essential for Pdr3-mediated basal expression of the PDR network genes, while SWI/SNF is essential for both basal and drug-induced expression. Also in the pathogenic fungus Candida glabrata, Rtt106 and SWI/SNF regulate drug-induced PDR gene expression. Consistently, loss of Rtt106 or SWI/SNF sensitises drug-resistant S. cerevisiae mutants and C. glabrata to antifungal drugs. Since they cooperatively drive PDR network gene expression, Rtt106 and SWI/SNF represent potential therapeutic targets to combat antifungal resistance.
Anopheles mosquitoes reveal new principles of 3D genome organization in insects
Authors: Lukyanchikova Varvara , Nuriddinov Miroslav , Belokopytova Polina , Taskina Alena , Liang Jiangtao , Reijnders Maarten J. M. F. , Ruzzante Livio , Feron Romain , Waterhouse Robert M. , Wu Yang , Mao Chunhong , Tu Zhijian , Sharakhov Igor V. , Fishman Veniamin 
Published: April 2022

AbstractChromosomes are hierarchically folded within cell nuclei into territories, domains and subdomains, but the functional importance and evolutionary dynamics of these hierarchies are poorly defined. Here, we comprehensively profile genome organizations of five Anopheles mosquito species and show how different levels of chromatin architecture influence each other. Patterns observed on Hi-C maps are associated with known cytological structures, epigenetic profiles, and gene expression levels. Evolutionary analysis reveals conservation of chromatin architecture within synteny blocks for tens of millions of years and enrichment of synteny breakpoints in regions with increased genomic insulation. However, in-depth analysis shows a confounding effect of gene density on both insulation and distribution of synteny breakpoints, suggesting limited causal relationship between breakpoints and regions with increased genomic insulation. At the level of individual loci, we identify specific, extremely long-ranged looping interactions, conserved for ~100 million years. We demonstrate that the mechanisms underlying these looping contacts differ from previously described Polycomb-dependent interactions and clustering of active chromatin.
Deforestation-induced climate change reduces carbon storage in remaining tropical forests
Authors: Li Yue , Brando Paulo M. , Morton Douglas C. , Lawrence David M. , Yang Hui , Randerson James T. 
Published: April 2022

AbstractBiophysical effects from deforestation have the potential to amplify carbon losses but are often neglected in carbon accounting systems. Here we use both Earth system model simulations and satellite–derived estimates of aboveground biomass to assess losses of vegetation carbon caused by the influence of tropical deforestation on regional climate across different continents. In the Amazon, warming and drying arising from deforestation result in an additional 5.1 ± 3.7% loss of aboveground biomass. Biophysical effects also amplify carbon losses in the Congo (3.8 ± 2.5%) but do not lead to significant additional carbon losses in tropical Asia due to its high levels of annual mean precipitation. These findings indicate that tropical forests may be undervalued in carbon accounting systems that neglect climate feedbacks from surface biophysical changes and that the positive carbon–climate feedback from deforestation-driven climate change is higher than the feedback originating from fossil fuel emissions.
Trade-off between tree planting and wetland conservation in China
Authors: Xi Yi , Peng Shushi , Liu Gang , Ducharne Agnès , Ciais Philippe , Prigent Catherine , Li Xinyu , Tang Xutao 
Published: April 2022

AbstractTrade-offs between tree planting programs and wetland conservation are unclear. Here, we employ satellite-derived inundation data and a process-based land surface model (ORCHIDEE-Hillslope) to investigate the impacts of tree planting on wetland dynamics in China for 2000–2016 and the potential impacts of near-term tree planting activities for 2017–2035. We find that 160,000–190,000 km2(25.3–25.6%) of historical tree planting over wetland grid cells has resulted in 1,300–1,500 km2(0.3–0.4%) net wetland loss. Compared to moist southern regions, the dry northern and western regions show a much higher sensitivity of wetland reduction to tree planting. With most protected wetlands in China located in the drier northern and western basins, continuing tree planting scenarios are projected to lead to a > 10% wetland loss relative to 2000 across 4–8 out of 38 national wetland nature reserves. Our work shows how spatial optimization can help the balance of tree planting and wetland conservation targets.
Lossless multi-scale constitutive elastic relations with artificial intelligence
Authors: Mianroodi Jaber Rezaei , Rezaei Shahed , Siboni Nima H. , Xu Bai-Xiang , Raabe Dierk 
Published: April 2022

AbstractA seamless and lossless transition of the constitutive description of the elastic response of materials between atomic and continuum scales has been so far elusive. Here we show how this problem can be overcome by using artificial intelligence (AI). A convolutional neural network (CNN) model is trained, by taking the structure image of a nanoporous material as input and the corresponding elasticity tensor, calculated from molecular statics (MS), as output. Trained with the atomistic data, the CNN model captures the size- and pore-dependency of the material’s elastic properties which, on the physics side, derive from its intrinsic stiffness as well as from surface relaxation and non-local effects. To demonstrate the accuracy and the efficiency of the trained CNN model, a finite element method (FEM)-based result of an elastically deformed nanoporous beam equipped with the CNN as constitutive law is compared with that obtained by a full atomistic simulation. The trained CNN model predicts the elasticity tensor in the test dataset with a root-mean-square error of 2.4 GPa (3.0% of the bulk modulus) when compared to atomistic calculations. On the other hand, the CNN model is about 230 times faster than the MS calculation and does not require changing simulation methods between different scales. The efficiency of the CNN evaluation together with the preservation of important atomistic effects makes the trained model an effective atomistically informed constitutive model for macroscopic simulations of nanoporous materials, optimization of nanostructures, and the solution of inverse problems.
A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia
Authors: Miyagawa Taku , Tanaka Susumu , Shimada Mihoko , Sakai Noriaki , Tanida Kotomi , Kotorii Nozomu , Kotorii Tatayu , Ariyoshi Yu , Hashizume Yuji , Ogi Kimihiro , Hiejima Hiroshi , Kanbayashi Takashi , Imanishi Aya , Ikegami Azusa , Kamei Yuichi , Hida Akiko , Wada Yamato , Miyamoto Masayuki , Takami Masanori , Kondo Hideaki , Tamura Yoshiyuki , Taniyama Yukari , Omata Naoto , Mizuno Tomoyuki , Moriya Shunpei , Furuya Hirokazu , Kato Mitsuhiro , Kato Kayoko , Ishigooka Jun , Tsuruta Kazuhito , Chiba Shigeru , Yamada Naoto , Okawa Masako , Hirata Koichi , Kuroda Kenji , Kume Kazuhiko , Uchimura Naohisa , Kitada Masaaki , Kodama Tohru , Inoue Yuichi , Nishino Seiji , Mishima Kazuo , Tokunaga Katsushi , Honda Makoto 
Published: April 2022

AbstractIdiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH. We performed a variation screening of the prepro-orexin/hypocretin and orexin receptors genes and an association study for IH in a Japanese population, with replication (598 patients and 9826 controls). We identified a rare missense variant (g.42184347T>C; p.Lys68Arg; rs537376938) in the cleavage site of prepro-orexin that was associated with IH (minor allele frequency of 1.67% in cases versus 0.32% in controls, P = 2.7 × 10−8, odds ratio = 5.36). Two forms of orexin (orexin-A and -B) are generated from cleavage of one precursor peptide, prepro-orexin. The difference in cleavage efficiency between wild-type (Gly-Lys-Arg; GKR) and mutant (Gly-Arg-Arg; GRR) peptides was examined by assays using proprotein convertase subtilisin/kexin (PCSK) type 1 and PCSK type 2. In both PCSK1 and PCSK2 assays, the cleavage efficiency of the mutant peptide was lower than that of the wild-type peptide. We also confirmed that the prepro-orexin peptides themselves transmitted less signaling through orexin receptors than mature orexin-A and orexin-B peptides. These results indicate that a subgroup of IH is associated with decreased orexin signaling, which is believed to be a hallmark of narcolepsy type 1.
The corrosion behavior of EW75 magnesium alloy in the research vessel KEXUE during the ocean voyage
Authors: Jiang Quantong , Lu Dongzhu , Cheng Liren , Liu Nazhen , Yang Lihui , Hou Baorong 
Published: April 2022

AbstractThe corrosion behavior of EW75 magnesium alloy in the Research Vessel KEXUE (RV KEXUE) during the ocean voyage was researched. The weight loss, corrosion depths, corrosion morphologies, and corrosion products were all analyzed. The mean weight loss rate of EW75 alloy Extrusion Surface was 0.0672 mg cm−2 y−1 (0.0903 mm y−1) after exposure corrosion tests, whereas that of Cross-section Surface was 0.0938 mg cm−2 y−1 (0.1537 mm y−1). Both extrusion direction and transverse direction of magnesium alloy samples occurred the brittle fracture in the harsh marine environment, and the mechanical strength fell precipitously after the exposure tests. The corrosion resistance of EW75 magnesium alloys obviously showed the anisotropy, which was due to the texture of the magnesium alloy in the microstructure. High salinity and high humidity environment led to a severe corrosion of EW75 magnesium alloys during exposure in the RV KEXUE during the ocean voyage. This study will provide the effective data for the service of magnesium alloys in typical marine atmospheric environment.