bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two novel venom proteins underlie divergent parasitic strategies between a generalist and a specialist parasite
Authors: Huang Jianhua , Chen Jiani , Fang Gangqi , Pang Lan , Zhou Sicong , Zhou Yuenan , Pan Zhongqiu , Zhang Qichao , Sheng Yifeng , Lu Yueqi , Liu Zhiguo , Zhang Yixiang , Li Guiyun , Shi Min , Chen Xuexin , Zhan Shuai 
Published: January 2021

AbstractParasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation.
Isolated copper single sites for high-performance electroreduction of carbon monoxide to multicarbon products
Authors: Bao Haihong , Qiu Yuan , Peng Xianyun , Wang Jia-ao , Mi Yuying , Zhao Shunzheng , Liu Xijun , Liu Yifan , Cao Rui , Zhuo Longchao , Ren Junqiang , Sun Jiaqiang , Luo Jun , Sun Xuping 
Published: January 2021

AbstractElectrochemical carbon monoxide reduction is a promising strategy for the production of value-added multicarbon compounds, albeit yielding diverse products with low selectivities and Faradaic efficiencies. Here, copper single atoms anchored to Ti3C2Tx MXene nanosheets are firstly demonstrated as effective and robust catalysts for electrochemical carbon monoxide reduction, achieving an ultrahigh selectivity of 98% for the formation of multicarbon products. Particularly, it exhibits a high Faradaic efficiency of 71% towards ethylene at −0.7 V versus the reversible hydrogen electrode, superior to the previously reported copper-based catalysts. Besides, it shows a stable activity during the 68-h electrolysis. Theoretical simulations reveal that atomically dispersed Cu–O3 sites favor the C–C coupling of carbon monoxide molecules to generate the key *CO-CHO species, and then induce the decreased free energy barrier of the potential-determining step, thus accounting for the high activity and selectivity of copper single atoms for carbon monoxide reduction.
Light quantum control of persisting Higgs modes in iron-based superconductors
Authors: Vaswani C. , Kang J. H. , Mootz M. , Luo L. , Yang X. , Sundahl C. , Cheng D. , Huang C. , Kim R. H. J. , Liu Z. , Collantes Y. G. , Hellstrom E. E. , Perakis I. E. , Eom C. B. , Wang J. 
Published: January 2021

AbstractThe Higgs mechanism, i.e., spontaneous symmetry breaking of the quantum vacuum, is a cross-disciplinary principle, universal for understanding dark energy, antimatter and quantum materials, from superconductivity to magnetism. Unlike one-band superconductors (SCs), a conceptually distinct Higgs amplitude mode can arise in multi-band, unconventional superconductors via strong interband Coulomb interaction, but is yet to be accessed. Here we discover such hybrid Higgs mode and demonstrate its quantum control by light in iron-based high-temperature SCs. Using terahertz (THz) two-pulse coherent spectroscopy, we observe a tunable amplitude mode coherent oscillation of the complex order parameter from coupled lower and upper bands. The nonlinear dependence of the hybrid Higgs mode on the THz driving fields is distinct from any known SC results: we observe a large reversible modulation of resonance strength, yet with a persisting mode frequency. Together with quantum kinetic modeling of a hybrid Higgs mechanism, distinct from charge-density fluctuations and without invoking phonons or disorder, our result provides compelling evidence for a light-controlled coupling between the electron and hole amplitude modes assisted by strong interband quantum entanglement. Such light-control of Higgs hybridization can be extended to probe many-body entanglement and hidden symmetries in other complex systems.
Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity
Authors: Sarvestani Samaneh K. , Signs Steven , Hu Bo , Yeu Yunku , Feng Hao , Ni Ying , Hill David R. , Fisher Robert C. , Ferrandon Sylvain , DeHaan Reece K. , Stiene Jennifer , Cruise Michael , Hwang Tae Hyun , Shen Xiling , Spence Jason R. , Huang Emina H. 
Published: January 2021

AbstractThe pathogenesis of ulcerative colitis (UC), a major type of inflammatory bowel disease, remains unknown. No model exists that adequately recapitulates the complexity of clinical UC. Here, we take advantage of induced pluripotent stem cells (iPSCs) to develop an induced human UC-derived organoid (iHUCO) model and compared it with the induced human normal organoid model (iHNO). Notably, iHUCOs recapitulated histological and functional features of primary colitic tissues, including the absence of acidic mucus secretion and aberrant adherens junctions in the epithelial barrier both in vitro and in vivo. We demonstrate that the CXCL8/CXCR1 axis was overexpressed in iHUCO but not in iHNO. As proof-of-principle, we show that inhibition of CXCL8 receptor by the small-molecule non-competitive inhibitor repertaxin attenuated the progression of UC phenotypes in vitro and in vivo. This patient-derived organoid model, containing both epithelial and stromal compartments, will generate new insights into the underlying pathogenesis of UC while offering opportunities to tailor interventions to the individual patient.
Important contributions of non-fossil fuel nitrogen oxides emissions
Authors: Song Wei , Liu Xue-Yan , Hu Chao-Chen , Chen Guan-Yi , Liu Xue-Jun , Walters Wendell W. , Michalski Greg , Liu Cong-Qiang 
Published: January 2021

AbstractSince the industrial revolution, it has been assumed that fossil-fuel combustions dominate increasing nitrogen oxide (NOx) emissions. However, it remains uncertain to the actual contribution of the non-fossil fuel NOxto total NOxemissions. Natural N isotopes of NO3−in precipitation (δ15Nw-NO3−) have been widely employed for tracing atmospheric NOxsources. Here, we compiled global δ15Nw-NO3−observations to evaluate the relative importance of fossil and non-fossil fuel NOxemissions. We found that regional differences in human activities directly influenced spatial-temporal patterns of δ15Nw-NO3−variations. Further, isotope mass-balance and bottom-up calculations suggest that the non-fossil fuel NOxaccounts for 55 ± 7% of total NOxemissions, reaching up to 21.6 ± 16.6Mt yr−1in East Asia, 7.4 ± 5.5Mt yr−1in Europe, and 21.8 ± 18.5Mt yr−1in North America, respectively. These results reveal the importance of non-fossil fuel NOxemissions and provide direct evidence for making strategies on mitigating atmospheric NOxpollution.
A comprehensive re-assessment of the association between vitamin D and cancer susceptibility using Mendelian randomization
Authors: Ong Jue-Sheng , Dixon-Suen Suzanne C. , Han Xikun , An Jiyuan ,   Esophageal Cancer Consortium, Fitzgerald Rebecca , Buas Matt , Gammon Marilie D. , Corley Douglas A. , Shaheen Nicholas J. , Hardie Laura J. , Bird Nigel C. , Reid Brian J. , Chow Wong-Ho , Risch Harvey A. , Ye Weimin , Liu Geoffrey , Romero Yvonne , Bernstein Leslie , Wu Anna H. , Whiteman David E. , Vaughan Thomas ,   23 and Me Research Team, Agee M. , Alipanahi B. , Auton A. , Bell R. K. , Bryc K. , Elson S. L. , Fontanillas P. , Furlotte N. A. , Hinds D. A. , Huber K. E. , Kleinman A. , Litterman N. K. , McIntyre M. H. , Mountain J. L. , Noblin E. S. , Northover C. A. M. , Pitts S. J. , Sathirapongsasuti J. Fah , Sazonova O. V. , Shelton J. F. , Shringarpure S. , Tian C. , Tung J. Y. , Vacic V. , Wilson C. H. , Liyanage Upekha , Dusingize Jean-Cluade , Schumacher Johannes , Gockel Ines , Böhmer Anne , Jankowski Janusz , Palles Claire , O’Mara Tracy , Spurdle Amanda , Law Matthew H. , Iles Mark M. , Pharoah Paul , Berchuck Andrew , Zheng Wei , Thrift Aaron P. , Olsen Catherine , Neale Rachel E. , Gharahkhani Puya , Webb Penelope M. , MacGregor Stuart 
Published: January 2021

AbstractPrevious Mendelian randomization (MR) studies on 25-hydroxyvitamin D (25(OH)D) and cancer have typically adopted a handful of variants and found no relationship between 25(OH)D and cancer; however, issues of horizontal pleiotropy cannot be reliably addressed. Using a larger set of variants associated with 25(OH)D (74 SNPs, up from 6 previously), we perform a unified MR analysis to re-evaluate the relationship between 25(OH)D and ten cancers. Our findings are broadly consistent with previous MR studies indicating no relationship, apart from ovarian cancers (OR 0.89; 95% C.I: 0.82 to 0.96 per 1 SD change in 25(OH)D concentration) and basal cell carcinoma (OR 1.16; 95% C.I.: 1.04 to 1.28). However, after adjustment for pigmentation related variables in a multivariable MR framework, the BCC findings were attenuated. Here we report that lower 25(OH)D is unlikely to be a causal risk factor for most cancers, with our study providing more precise confidence intervals than previously possible.
BRD4-mediated repression of p53 is a target for combination therapy in AML
Authors: Latif Anne-Louise , Newcombe Ashley , Li Sha , Gilroy Kathryn , Robertson Neil A. , Lei Xue , Stewart Helen J. S. , Cole John , Terradas Maria Terradas , Rishi Loveena , McGarry Lynn , McKeeve Claire , Reid Claire , Clark William , Campos Joana , Kirschner Kristina , Davis Andrew , Lopez Jonathan , Sakamaki Jun-ichi , Morton Jennifer P. , Ryan Kevin M. , Tait Stephen W. G. , Abraham Sheela A. , Holyoake Tessa , Higgins Brian , Huang Xu , Blyth Karen , Copland Mhairi , Chevassut Timothy J. T. , Keeshan Karen , Adams Peter D. 
Published: January 2021

AbstractAcute myeloid leukemia (AML) is a typically lethal molecularly heterogeneous disease, with few broad-spectrum therapeutic targets. Unusually, most AML retain wild-type TP53, encoding the pro-apoptotic tumor suppressor p53. MDM2 inhibitors (MDM2i), which activate wild-type p53, and BET inhibitors (BETi), targeting the BET-family co-activator BRD4, both show encouraging pre-clinical activity, but limited clinical activity as single agents. Here, we report enhanced toxicity of combined MDM2i and BETi towards AML cell lines, primary human blasts and mouse models, resulting from BETi’s ability to evict an unexpected repressive form of BRD4 from p53 target genes, and hence potentiate MDM2i-induced p53 activation. These results indicate that wild-type TP53 and a transcriptional repressor function of BRD4 together represent a potential broad-spectrum synthetic therapeutic vulnerability for AML.
BET inhibition disrupts transcription but retains enhancer-promoter contact
Authors: Crump Nicholas T. , Ballabio Erica , Godfrey Laura , Thorne Ross , Repapi Emmanouela , Kerry Jon , Tapia Marta , Hua Peng , Lagerholm Christoffer , Filippakopoulos Panagis , Davies James O. J. , Milne Thomas A. 
Published: January 2021

AbstractEnhancers are DNA sequences that enable complex temporal and tissue-specific regulation of genes in higher eukaryotes. Although it is not entirely clear how enhancer-promoter interactions can increase gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential for the maintenance of gene expression. Bromodomain and Extra-Terminal domain (BET) and Mediator proteins have been shown capable of forming phase condensates and are thought to be essential for super-enhancer function. Here, we show that targeting of cells with inhibitors of BET proteins or pharmacological degradation of BET protein Bromodomain-containing protein 4 (BRD4) has a strong impact on transcription but very little impact on enhancer-promoter interactions. Dissolving phase condensates reduces BRD4 and Mediator binding at enhancers and can also strongly affect gene transcription, without disrupting enhancer-promoter interactions. These results suggest that activation of transcription and maintenance of enhancer-promoter interactions are separable events. Our findings further indicate that enhancer-promoter interactions are not dependent on high levels of BRD4 and Mediator, and are likely maintained by a complex set of factors including additional activator complexes and, at some sites, CTCF and cohesin.
Engineering of a bona fide light-operated calcium channel
Authors: He Lian , Wang Liuqing , Zeng Hongxiang , Tan Peng , Ma Guolin , Zheng Sisi , Li Yaxin , Sun Lin , Dou Fei , Siwko Stefan , Huang Yun , Wang Youjun , Zhou Yubin 
Published: January 2021

AbstractThe current optogenetic toolkit lacks a robust single-component Ca2+-selective ion channel tailored for remote control of Ca2+ signaling in mammals. Existing tools are either derived from engineered channelrhodopsin variants without strict Ca2+ selectivity or based on the stromal interaction molecule 1 (STIM1) that might crosstalk with other targets. Here, we describe the design of a light-operated Ca2+ channel (designated LOCa) by inserting a plant-derived photosensory module into the intracellular loop of an engineered ORAI1 channel. LOCa displays biophysical features reminiscent of the ORAI1 channel, which enables precise optical control over Ca2+ signals and hallmark Ca2+-dependent physiological responses. Furthermore, we demonstrate the use of LOCa to modulate aberrant hematopoietic stem cell self-renewal, transcriptional programming, cell suicide, as well as neurodegeneration in a Drosophila model of amyloidosis.
Moiré metrology of energy landscapes in van der Waals heterostructures
Authors: Halbertal Dorri , Finney Nathan R. , Sunku Sai S. , Kerelsky Alexander , Rubio-Verdú Carmen , Shabani Sara , Xian Lede , Carr Stephen , Chen Shaowen , Zhang Charles , Wang Lei , Gonzalez-Acevedo Derick , McLeod Alexander S. , Rhodes Daniel , Watanabe Kenji , Taniguchi Takashi , Kaxiras Efthimios , Dean Cory R. , Hone James C. , Pasupathy Abhay N. , Kennes Dante M. , Rubio Angel , Basov D. N. 
Published: January 2021

AbstractThe emerging field of twistronics, which harnesses the twist angle between two-dimensional materials, represents a promising route for the design of quantum materials, as the twist-angle-induced superlattices offer means to control topology and strong correlations. At the small twist limit, and particularly under strain, as atomic relaxation prevails, the emergent moiré superlattice encodes elusive insights into the local interlayer interaction. Here we introduce moiré metrology as a combined experiment-theory framework to probe the stacking energy landscape of bilayer structures at the 0.1 meV/atom scale, outperforming the gold-standard of quantum chemistry. Through studying the shapes of moiré domains with numerous nano-imaging techniques, and correlating with multi-scale modelling, we assess and refine first-principle models for the interlayer interaction. We document the prowess of moiré metrology for three representative twisted systems: bilayer graphene, double bilayer graphene and H-stacked MoSe2/WSe2. Moiré metrology establishes sought after experimental benchmarks for interlayer interaction, thus enabling accurate modelling of twisted multilayers.
Spite is contagious in dynamic networks
Authors: Fulker Zachary , Forber Patrick , Smead Rory , Riedl Christoph 
Published: January 2021

AbstractSpite, costly behavior that harms others, presents an evolutionary puzzle: given that both the actor and recipient do worse, how could it emerge? We show that dynamically evolving interaction networks provide a novel explanation for the evolution of costly harm. Previous work has shown that anti-correlated interaction (e.g., negative assortment or negative relatedness) among behavioral strategies in populations can lead to the evolution of costly harm. We show that these approaches are blind to important features of interaction brought about by a co-evolution of network and behavior and that these features enable the emergence of spite. We analyze a new model in which agents can inflict harm on others at a cost to themselves, and simultaneously learn how to behave and with whom to interact. We find spite emerges reliably under a wide range of conditions. Our model reveals that when interactions occur in dynamic networks the population can exhibit correlated and anti-correlated behavioral interactions simultaneously, something not possible in standard models. In dynamic networks spite evolves due to transient and partial anti-correlated interaction, even when other behaviors are positively correlated and average degree of correlated interaction in the population is low.
Isolation of MERS-related coronavirus from lesser bamboo bats that uses DPP4 and infects human-DPP4-transgenic mice
Authors: Lau Susanna K. P. , Fan Rachel Y. Y. , Zhu Longchao , Li Kenneth S. M. , Wong Antonio C. P. , Luk Hayes K. H. , Wong Emily Y. M. , Lam Carol S. F. , Lo George C. S. , Fung Joshua , He Zirong , Fok Felix C. H. , Au-Yeung Rex K. H. , Zhang Libiao , Kok Kin-Hang , Yuen Kwok-Yung , Woo Patrick C. Y. 
Published: January 2021

AbstractWhile a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.
Cooperative function of synaptophysin and synapsin in the generation of synaptic vesicle-like clusters in non-neuronal cells
Authors: Park Daehun , Wu Yumei , Lee Sang-Eun , Kim Goeun , Jeong Seonyoung , Milovanovic Dragomir , De Camilli Pietro , Chang Sunghoe 
Published: January 2021

AbstractClusters of tightly packed synaptic vesicles (SVs) are a defining feature of nerve terminals. While SVs are mobile within the clusters, the clusters have no boundaries consistent with a liquid phase. We previously found that purified synapsin, a peripheral SV protein, can assemble into liquid condensates and trap liposomes into them. How this finding relates to the physiological formation of SV clusters in living cells remains unclear. Here, we report that synapsin alone, when expressed in fibroblasts, has a diffuse cytosolic distribution. However, when expressed together with synaptophysin, an integral SV membrane protein previously shown to be localized on small synaptic-like microvesicles when expressed in non-neuronal cells, is sufficient to organize such vesicles in clusters highly reminiscent of SV clusters and with liquid-like properties. This minimal reconstitution system can be a powerful model to gain mechanistic insight into the assembly of structures which are of fundamental importance in synaptic transmission.
Cryo-EM structure of Helicobacter pylori urease with an inhibitor in the active site at 2.0 Å resolution
Authors: Cunha Eva S. , Chen Xiaorui , Sanz-Gaitero Marta , Mills Deryck J. , Luecke Hartmut 
Published: January 2021

AbstractInfection of the human stomach by Helicobacter pylori remains a worldwide problem and greatly contributes to peptic ulcer disease and gastric cancer. Without active intervention approximately 50% of the world population will continue to be infected with this gastric pathogen. Current eradication, called triple therapy, entails a proton-pump inhibitor and two broadband antibiotics, however resistance to either clarithromycin or metronidazole is greater than 25% and rising. Therefore, there is an urgent need for a targeted, high-specificity eradication drug. Gastric infection by H. pylori depends on the expression of a nickel-dependent urease in the cytoplasm of the bacteria. Here, we report the 2.0 Å resolution structure of the 1.1 MDa urease in complex with an inhibitor by cryo-electron microscopy and compare it to a β-mercaptoethanol-inhibited structure at 2.5 Å resolution. The structural information is of sufficient detail to aid in the development of inhibitors with high specificity and affinity.
CXCR5 CAR-T cells simultaneously target B cell non-Hodgkin’s lymphoma and tumor-supportive follicular T helper cells
Authors: Bunse Mario , Pfeilschifter Janina , Bluhm Julia , Zschummel Maria , Joedicke Jara J. , Wirges Anthea , Stark Helen , Kretschmer Vivien , Chmielewski Markus , Uckert Wolfgang , Abken Hinrich , Westermann Jörg , Rehm Armin , Höpken Uta E. 
Published: January 2021

AbstractCAR-T cell therapy targeting CD19 demonstrated strong activity against advanced B cell leukemia, however shows less efficacy against lymphoma with nodal dissemination. To target both B cell Non-Hodgkin’s lymphoma (B-NHLs) and follicular T helper (Tfh) cells in the tumor microenvironment (TME), we apply here a chimeric antigen receptor (CAR) that recognizes human CXCR5 with high avidity. CXCR5, physiologically expressed on mature B and Tfh cells, is also highly expressed on nodal B-NHLs. Anti-CXCR5 CAR-T cells eradicate B-NHL cells and lymphoma-supportive Tfh cells more potently than CD19 CAR-T cells in vitro, and they efficiently inhibit lymphoma growth in a murine xenograft model. Administration of anti-murine CXCR5 CAR-T cells in syngeneic mice specifically depletes endogenous and malignant B and Tfh cells without unexpected on-target/off-tumor effects. Collectively, anti-CXCR5 CAR-T cells provide a promising treatment strategy for nodal B-NHLs through the simultaneous elimination of lymphoma B cells and Tfh cells of the tumor-supporting TME.