bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrical conductivity of warm dense silica from double-shock experiments
Authors: Guarguaglini M. , Soubiran F. , Hernandez J.-A. , Benuzzi-Mounaix A. , Bolis R. , Brambrink E. , Vinci T. , Ravasio A. 
Published: February 2021

AbstractUnderstanding materials behaviour under extreme thermodynamic conditions is fundamental in many branches of science, including High-Energy-Density physics, fusion research, material and planetary science. Silica (SiO2) is of primary importance as a key component of rocky planets’ mantles. Dynamic compression is the most promising approach to explore molten silicates under extreme conditions. Although most experimental studies are restricted to the Hugoniot curve, a wider range of conditions must be reached to distill temperature and pressure effects. Here we present direct measurements of equation of state and two-colour reflectivity of double-shocked α-quartz on a large ensemble of thermodynamic conditions, which were until now unexplored. Combining experimental reflectivity data with numerical simulations we determine the electrical conductivity. The latter is almost constant with pressure while highly dependent on temperature, which is consistent with simulations results. Based on our findings, we conclude that dynamo processes are likely in Super-Earths’ mantles.
Carbon emission from Western Siberian inland waters
Authors: Karlsson Jan , Serikova Svetlana , Vorobyev Sergey N. , Rocher-Ros Gerard , Denfeld Blaize , Pokrovsky Oleg S. 
Published: February 2021

AbstractHigh-latitude regions play a key role in the carbon (C) cycle and climate system. An important question is the degree of mobilization and atmospheric release of vast soil C stocks, partly stored in permafrost, with amplified warming of these regions. A fraction of this C is exported to inland waters and emitted to the atmosphere, yet these losses are poorly constrained and seldom accounted for in assessments of high-latitude C balances. This is particularly relevant for Western Siberia, with its extensive peatland C stocks, which can be strongly sensitive to the ongoing changes in climate. Here we quantify C emission from inland waters, including the Ob’ River (Arctic’s largest watershed), across all permafrost zones of Western Siberia. We show that the inland water C emission is high (0.08–0.10 Pg C yr−1) and of major significance in the regional C cycle, largely exceeding (7–9 times) C export to the Arctic Ocean and reaching nearly half (35–50%) of the region’s land C uptake. This important role of C emission from inland waters highlights the need for coupled land–water studies to understand the contemporary C cycle and its response to warming.
Control of zeolite microenvironment for propene synthesis from methanol
Authors: Lin Longfei , Fan Mengtian , Sheveleva Alena M. , Han Xue , Tang Zhimou , Carter Joseph H. , da Silva Ivan , Parlett Christopher M. A. , Tuna Floriana , McInnes Eric J. L. , Sastre German , Rudić Svemir , Cavaye Hamish , Parker Stewart F. , Cheng Yongqiang , Daemen Luke L. , Ramirez-Cuesta Anibal J. , Attfield Martin P. , Liu Yueming , Tang Chiu C. , Han Buxing , Yang Sihai 
Published: February 2021

AbstractOptimising the balance between propene selectivity, propene/ethene ratio and catalytic stability and unravelling the explicit mechanism on formation of the first carbon–carbon bond are challenging goals of great importance in state-of-the-art methanol-to-olefin (MTO) research. We report a strategy to finely control the nature of active sites within the pores of commercial MFI-zeolites by incorporating tantalum(V) and aluminium(III) centres into the framework. The resultant TaAlS-1 zeolite exhibits simultaneously remarkable propene selectivity (51%), propene/ethene ratio (8.3) and catalytic stability (>50 h) at full methanol conversion. In situ synchrotron X-ray powder diffraction, X-ray absorption spectroscopy and inelastic neutron scattering coupled with DFT calculations reveal that the first carbon–carbon bond is formed between an activated methanol molecule and a trimethyloxonium intermediate. The unprecedented cooperativity between tantalum(V) and Brønsted acid sites creates an optimal microenvironment for efficient conversion of methanol and thus greatly promotes the application of zeolites in the sustainable manufacturing of light olefins.
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
Authors: Muskens Ivo S. , Li Shaobo , Jackson Thomas , Elliot Natalina , Hansen Helen M. , Myint Swe Swe , Pandey Priyatama , Schraw Jeremy M. , Roy Ritu , Anguiano Joaquin , Goudevenou Katerina , Siegmund Kimberly D. , Lupo Philip J. , de Bruijn Marella F. T. R. , Walsh Kyle M. , Vyas Paresh , Ma Xiaomei , Roy Anindita , Roberts Irene , Wiemels Joseph L. , de Smith Adam J. 
Published: February 2021

AbstractDown syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10−8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome.
Integrative molecular characterization of sarcomatoid and rhabdoid renal cell carcinoma
Authors: Bakouny Ziad , Braun David A. , Shukla Sachet A. , Pan Wenting , Gao Xin , Hou Yue , Flaifel Abdallah , Tang Stephen , Bosma-Moody Alice , He Meng Xiao , Vokes Natalie , Nyman Jackson , Xie Wanling , Nassar Amin H. , Abou Alaiwi Sarah , Flippot Ronan , Bouchard Gabrielle , Steinharter John A. , Nuzzo Pier Vitale , Ficial Miriam , Sant’Angelo Miriam , Forman Juliet , Berchuck Jacob E. , Dudani Shaan , Bi Kevin , Park Jihye , Camp Sabrina , Sticco-Ivins Maura , Hirsch Laure , Baca Sylvan C. , Wind-Rotolo Megan , Ross-Macdonald Petra , Sun Maxine , Lee Gwo-Shu Mary , Chang Steven L. , Wei Xiao X. , McGregor Bradley A. , Harshman Lauren C. , Genovese Giannicola , Ellis Leigh , Pomerantz Mark , Hirsch Michelle S. , Freedman Matthew L. , Atkins Michael B. , Wu Catherine J. , Ho Thai H. , Linehan W. Marston , McDermott David F. , Heng Daniel Y. C. , Viswanathan Srinivas R. , Signoretti Sabina , Van Allen Eliezer M. , Choueiri Toni K. 
Published: February 2021

AbstractSarcomatoid and rhabdoid (S/R) renal cell carcinoma (RCC) are highly aggressive tumors with limited molecular and clinical characterization. Emerging evidence suggests immune checkpoint inhibitors (ICI) are particularly effective for these tumors, although the biological basis for this property is largely unknown. Here, we evaluate multiple clinical trial and real-world cohorts of S/R RCC to characterize their molecular features, clinical outcomes, and immunologic characteristics. We find that S/R RCC tumors harbor distinctive molecular features that may account for their aggressive behavior, including BAP1 mutations, CDKN2A deletions, and increased expression of MYC transcriptional programs. We show that these tumors are highly responsive to ICI and that they exhibit an immune-inflamed phenotype characterized by immune activation, increased cytotoxic immune infiltration, upregulation of antigen presentation machinery genes, and PD-L1 expression. Our findings build on prior work and shed light on the molecular drivers of aggressivity and responsiveness to ICI of S/R RCC.
C-STABILITY an innovative modeling framework to leverage the continuous representation of organic matter
Authors: Sainte-Marie Julien , Barrandon Matthieu , Saint-André Laurent , Gelhaye Eric , Martin Francis , Derrien Delphine 
Published: February 2021

AbstractThe understanding of soil organic matter (SOM) dynamics has considerably advanced in recent years. It was previously assumed that most SOM consisted of recalcitrant compounds, whereas the emerging view considers SOM as a range of polymers continuously processed into smaller molecules by decomposer enzymes. Mainstreaming this new paradigm in current models is challenging because of their ill-adapted framework. We propose the C-STABILITY model to resolve this issue. Its innovative framework combines compartmental and continuous modeling approaches to accurately reproduce SOM cycling processes. C-STABILITY emphasizes the influence of substrate accessibility on SOM turnover and makes enzymatic and microbial biotransformations of substrate explicit. Theoretical simulations provide new insights on how depolymerization and decomposers ecology impact organic matter chemistry and amount during decomposition and at steady state. The flexible mathematical structure of C-STABILITY offers a promising foundation for exploring new mechanistic hypotheses and supporting the design of future experiments.
Efficacy and tolerability of bevacizumab in patients with severe Covid-19
Authors: Pang Jiaojiao , Xu Feng , Aondio Gianmarco , Li Yu , Fumagalli Alberto , Lu Ming , Valmadre Giuseppe , Wei Jie , Bian Yuan , Canesi Margherita , Damiani Giovanni , Zhang Yuan , Yu Dexin , Chen Jun , Ji Xiang , Sui Wenhai , Wang Bailu , Wu Shuo , Kovacs Attila , Revera Miriam , Wang Hao , Jing Xu , Zhang Ying , Chen Yuguo , Cao Yihai 
Published: February 2021

AbstractOn the basis of Covid-19-induced pulmonary pathological and vascular changes, we hypothesize that the anti-vascular endothelial growth factor (VEGF) drug bevacizumab might be beneficial for treating Covid-19 patients. From Feb 15 to April 5, 2020, we conducted a single-arm trial (NCT04275414) and recruited 26 patients from 2-centers (China and Italy) with severe Covid-19, with respiratory rate ≥30 times/min, oxygen saturation ≤93% with ambient air, or partial arterial oxygen pressure to fraction of inspiration O2 ratio (PaO2/FiO2) >100 mmHg and ≤300 mmHg, and diffuse pneumonia confirmed by chest imaging. Followed up for 28 days. Among these, bevacizumab plus standard care markedly improves the PaO2/FiO2 ratios at days 1 and 7. By day 28, 24 (92%) patients show improvement in oxygen-support status, 17 (65%) patients are discharged, and none show worsen oxygen-support status nor die. Significant reduction of lesion areas/ratios are shown in chest computed tomography (CT) or X-ray within 7 days. Of 14 patients with fever, body temperature normalizes within 72 h in 13 (93%) patients. Relative to comparable controls, bevacizumab shows clinical efficacy by improving oxygenation and shortening oxygen-support duration. Our findings suggest bevacizumab plus standard care is highly beneficial for patients with severe Covid-19. Randomized controlled trial is warranted.
Structures of active-state orexin receptor 2 rationalize peptide and small-molecule agonist recognition and receptor activation
Authors: Hong Chuan , Byrne Noel J. , Zamlynny Beata , Tummala Srivanya , Xiao Li , Shipman Jennifer M. , Partridge Andrea T. , Minnick Christina , Breslin Michael J. , Rudd Michael T. , Stachel Shawn J. , Rada Vanessa L. , Kern Jeffrey C. , Armacost Kira A. , Hollingsworth Scott A. , O’Brien Julie A. , Hall Dawn L. , McDonald Terrence P. , Strickland Corey , Brooun Alexei , Soisson Stephen M. , Hollenstein Kaspar 
Published: February 2021

AbstractNarcolepsy type 1 (NT1) is a chronic neurological disorder that impairs the brain’s ability to control sleep-wake cycles. Current therapies are limited to the management of symptoms with modest effectiveness and substantial adverse effects. Agonists of the orexin receptor 2 (OX2R) have shown promise as novel therapeutics that directly target the pathophysiology of the disease. However, identification of drug-like OX2R agonists has proven difficult. Here we report cryo-electron microscopy structures of active-state OX2R bound to an endogenous peptide agonist and a small-molecule agonist. The extended carboxy-terminal segment of the peptide reaches into the core of OX2R to stabilize an active conformation, while the small-molecule agonist binds deep inside the orthosteric pocket, making similar key interactions. Comparison with antagonist-bound OX2R suggests a molecular mechanism that rationalizes both receptor activation and inhibition. Our results enable structure-based discovery of therapeutic orexin agonists for the treatment of NT1 and other hypersomnia disorders.
Phylogenetic analyses suggest centipede venom arsenals were repeatedly stocked by horizontal gene transfer
Authors: Undheim Eivind A. B. , Jenner Ronald A. 
Published: February 2021

AbstractVenoms have evolved over a hundred times in animals. Venom toxins are thought to evolve mostly by recruitment of endogenous proteins with physiological functions. Here we report phylogenetic analyses of venom proteome-annotated venom gland transcriptome data, assisted by genomic analyses, to show that centipede venoms have recruited at least five gene families from bacterial and fungal donors, involving at least eight horizontal gene transfer events. These results establish centipedes as currently the only known animals with venoms used in predation and defence that contain multiple gene families derived from horizontal gene transfer. The results also provide the first evidence for the implication of horizontal gene transfer in the evolutionary origin of venom in an animal lineage. Three of the bacterial gene families encode virulence factors, suggesting that horizontal gene transfer can provide a fast track channel for the evolution of novelty by the exaptation of bacterial weapons into animal venoms.
Genetics of nodulation in Aeschynomene evenia uncovers mechanisms of the rhizobium–legume symbiosis
Authors: Quilbé Johan , Lamy Léo , Brottier Laurent , Leleux Philippe , Fardoux Joël , Rivallan Ronan , Benichou Thomas , Guyonnet Rémi , Becana Manuel , Villar Irene , Garsmeur Olivier , Hufnagel Bárbara , Delteil Amandine , Gully Djamel , Chaintreuil Clémence , Pervent Marjorie , Cartieaux Fabienne , Bourge Mickaël , Valentin Nicolas , Martin Guillaume , Fontaine Loïc , Droc Gaëtan , Dereeper Alexis , Farmer Andrew , Libourel Cyril , Nouwen Nico , Gressent Frédéric , Mournet Pierre , D’Hont Angélique , Giraud Eric , Klopp Christophe , Arrighi Jean-François 
Published: February 2021

AbstractAmong legumes (Fabaceae) capable of nitrogen-fixing nodulation, several Aeschynomene spp. use a unique symbiotic process that is independent of Nod factors and infection threads. They are also distinctive in developing root and stem nodules with photosynthetic bradyrhizobia. Despite the significance of these symbiotic features, their understanding remains limited. To overcome such limitations, we conduct genetic studies of nodulation in Aeschynomene evenia, supported by the development of a genome sequence for A. evenia and transcriptomic resources for 10 additional Aeschynomene spp. Comparative analysis of symbiotic genes substantiates singular mechanisms in the early and late nodulation steps. A forward genetic screen also shows that AeCRK, coding a receptor-like kinase, and the symbiotic signaling genes AePOLLUX, AeCCamK, AeCYCLOPS, AeNSP2, and AeNIN are required to trigger both root and stem nodulation. This work demonstrates the utility of the A. evenia model and provides a cornerstone to unravel mechanisms underlying the rhizobium–legume symbiosis.
Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy
Authors: Yang Riyao , Sun Linlin , Li Ching-Fei , Wang Yu-Han , Yao Jun , Li Hui , Yan Meisi , Chang Wei-Chao , Hsu Jung-Mao , Cha Jong-Ho , Hsu Jennifer L. , Chou Cheng-Wei , Sun Xian , Deng Yalan , Chou Chao-Kai , Yu Dihua , Hung Mien-Chie 
Published: February 2021

AbstractThe two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1+TIM-3+ T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3+ cytotoxic CD8 T cells and immunosuppressive regulatory T cells (Treg cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes Treg cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.
Ph2 encodes the mismatch repair protein MSH7-3D that inhibits wheat homoeologous recombination
Authors: Serra Heïdi , Svačina Radim , Baumann Ute , Whitford Ryan , Sutton Tim , Bartoš Jan , Sourdille Pierre 
Published: February 2021

AbstractMeiotic recombination is a critical process for plant breeding, as it creates novel allele combinations that can be exploited for crop improvement. In wheat, a complex allohexaploid that has a diploid-like behaviour, meiotic recombination between homoeologous or alien chromosomes is suppressed through the action of several loci. Here, we report positional cloning of Pairing homoeologous 2 (Ph2) and functional validation of the wheat DNA mismatch repair protein MSH7-3D as a key inhibitor of homoeologous recombination, thus solving a half-century-old question. Similar to ph2 mutant phenotype, we show that mutating MSH7-3D induces a substantial increase in homoeologous recombination (up to 5.5 fold) in wheat-wild relative hybrids, which is also associated with a reduction in homologous recombination. These data reveal a role for MSH7-3D in meiotic stabilisation of allopolyploidy and provides an opportunity to improve wheat’s genetic diversity through alien gene introgression, a major bottleneck facing crop improvement.
Nonenzymatic polymerase-like template-directed synthesis of acyclic l-threoninol nucleic acid
Authors: Murayama Keiji , Okita Hikari , Kuriki Takumi , Asanuma Hiroyuki 
Published: February 2021

AbstractEvolution of xeno nucleic acid (XNA) world essentially requires template-directed synthesis of XNA polymers. In this study, we demonstrate template-directed synthesis of an acyclic XNA, acyclicl-threoninol nucleic acid (l-aTNA), via chemical ligation mediated by N-cyanoimidazole. The ligation of an l-aTNA fragment on an l-aTNA template is significantly faster and occurs in considerably higher yield than DNA ligation. Both l-aTNA ligation on a DNA template and DNA ligation on an l-aTNA template are also observed. High efficiency ligation of trimer l-aTNA fragments to a template-bound primer is achieved. Furthermore, a pseudo primer extension reaction is demonstrated using a pool of random l-aTNA trimers as substrates. To the best of our knowledge, this is the first example of polymerase-like primer extension of XNA with all four nucleobases, generating phosphodiester bonding without any special modification. This technique paves the way for a genetic system of the l-aTNA world.
IL-22-dependent dysbiosis and mononuclear phagocyte depletion contribute to steroid-resistant gut graft-versus-host disease in mice
Authors: Song Qingxiao , Wang Xiaoning , Wu Xiwei , Kang Tae Hyuk , Qin Hanjun , Zhao Dongchang , Jenq Robert R. , van den Brink Marcel R. M. , Riggs Arthur D. , Martin Paul J. , Chen Yuan-Zhong , Zeng Defu 
Published: February 2021

AbstractEfforts to improve the prognosis of steroid-resistant gut acute graft-versus-host-disease (SR-Gut-aGVHD) have suffered from poor understanding of its pathogenesis. Here we show that the pathogenesis of SR-Gut-aGVHD is associated with reduction of IFN-γ+ Th/Tc1 cells and preferential expansion of IL-17−IL-22+ Th/Tc22 cells. The IL-22 from Th/Tc22 cells causes dysbiosis in a Reg3γ-dependent manner. Transplantation of IFN-γ-deficient donor CD8+ T cells in the absence of CD4+ T cells produces a phenocopy of SR-Gut-aGVHD. IFN-γ deficiency in donor CD8+ T cells also leads to a PD-1-dependent depletion of intestinal protective CX3CR1hi mononuclear phagocytes (MNP), which also augments expansion of Tc22 cells. Supporting the dual regulation, simultaneous dysbiosis induction and depletion of CX3CR1hi MNP results in full-blown Gut-aGVHD. Our results thus provide insights into SR-Gut-aGVHD pathogenesis and suggest the potential efficacy of IL-22 antagonists and IFN-γ agonists in SR-Gut-aGVHD therapy.
Photo thermal effect graphene detector featuring 105 Gbit s−1 NRZ and 120 Gbit s−1 PAM4 direct detection
Authors: Marconi S. , Giambra M. A. , Montanaro A. , Mišeikis V. , Soresi S. , Tirelli S. , Galli P. , Buchali F. , Templ W. , Coletti C. , Sorianello V. , Romagnoli M. 
Published: February 2021

AbstractOne of the main challenges of next generation optical communication is to increase the available bandwidth while reducing the size, cost and power consumption of photonic integrated circuits. Graphene has been recently proposed to be integrated with silicon photonics to meet these goals because of its high mobility, fast carrier dynamics and ultra-broadband optical properties. We focus on graphene photodetectors for high speed datacom and telecom applications based on the photo-thermo-electric effect, allowing for direct optical power to voltage conversion, zero dark current, and ultra-fast operation. We report on a chemical vapour deposition graphene photodetector based on the photo-thermoelectric effect, integrated on a silicon waveguide, providing frequency response >65 GHz and optimized to be interfaced to a 50 Ω voltage amplifier for direct voltage amplification. We demonstrate a system test leading to direct detection of 105 Gbit s−1non-return to zero and 120 Gbit s−14-level pulse amplitude modulation optical signals.
Experimental quantum homomorphic encryption
Authors: Zeuner Jonas , Pitsios Ioannis , Tan Si-Hui , Sharma Aditya N. , Fitzsimons Joseph F. , Osellame Roberto , Walther Philip 
Published: February 2021

AbstractQuantum computers promise not only to outperform classical machines for certain important tasks, but also to preserve privacy of computation. For example, the blind quantum computing protocol enables secure delegated quantum computation, where a client can protect the privacy of their data and algorithms from a quantum server assigned to run the computation. However, this security comes with the practical limitation that the client and server must communicate after each step of computation. A practical alternative is homomorphic encryption, which does not require any interactions, while providing quantum-enhanced data security for a variety of computations. In this scenario, the server specifies the computation to be performed, and the client provides only the input data, thus enabling secure noninteractive computation. Here, we demonstrate homomorphic-encrypted quantum computing with unitary transformations of individual qubits, as well as multi-qubit quantum walk computations using single-photon states and non-birefringent integrated optics. The client encrypts their input in the photons’ polarization state, while the server performs the computation using the path degree of freedom. Our demonstration using integrated quantum photonics underlines the applicability of homomorphic-encrypted quantum computations, and shows the potential for delegated quantum computing using photons.