bluuebunny/crossref_metadata_2025_split huggingface dataset:
Infrared nanospectroscopy reveals the molecular interaction fingerprint of an aggregation inhibitor with single Aβ42 oligomers
Authors: Ruggeri Francesco Simone , Habchi Johnny , Chia Sean , Horne Robert I. , Vendruscolo Michele , Knowles Tuomas P. J. 
Published: January 2021

AbstractSignificant efforts have been devoted in the last twenty years to developing compounds that can interfere with the aggregation pathways of proteins related to misfolding disorders, including Alzheimer’s and Parkinson’s diseases. However, no disease-modifying drug has become available for clinical use to date for these conditions. One of the main reasons for this failure is the incomplete knowledge of the molecular mechanisms underlying the process by which small molecules interact with protein aggregates and interfere with their aggregation pathways. Here, we leverage the single molecule morphological and chemical sensitivity of infrared nanospectroscopy to provide the first direct measurement of the structure and interaction between single Aβ42 oligomeric and fibrillar species and an aggregation inhibitor, bexarotene, which is able to prevent Aβ42 aggregation in vitro and reverses its neurotoxicity in cell and animal models of Alzheimer’s disease. Our results demonstrate that the carboxyl group of this compound interacts with Aβ42 aggregates through a single hydrogen bond. These results establish infrared nanospectroscopy as a powerful tool in structure-based drug discovery for protein misfolding diseases.
Gene therapy via canalostomy approach preserves auditory and vestibular functions in a mouse model of Jervell and Lange-Nielsen syndrome type 2
Authors: Wu Xuewen , Zhang Li , Li Yihui , Zhang Wenjuan , Wang Jianjun , Cai Cuiyun , Lin Xi 
Published: January 2021

AbstractMutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.
Evolution of DNA methylome from precancerous lesions to invasive lung adenocarcinomas
Authors: Hu Xin , Estecio Marcos R. , Chen Runzhe , Reuben Alexandre , Wang Linghua , Fujimoto Junya , Carrot-Zhang Jian , McGranahan Nicholas , Ying Lisha , Fukuoka Junya , Chow Chi-Wan , Pham Hoa H. N. , Godoy Myrna C. B. , Carter Brett W. , Behrens Carmen , Zhang Jianhua , Antonoff Mara B. , Sepesi Boris , Lu Yue , Pass Harvey I. , Kadara Humam , Scheet Paul , Vaporciyan Ara A. , Heymach John V. , Wistuba Ignacio I. , Lee J. Jack , Futreal P. Andrew , Su Dan , Issa Jean-Pierre J. , Zhang Jianjun 
Published: January 2021

AbstractThe evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis of lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing of invasive lung adenocarcinoma and its precursors, atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. We observe gradual increase of methylation aberrations and significantly higher level of methylation ITH in later-stage lesions. The phylogenetic patterns inferred from methylation aberrations resemble those based on somatic mutations suggesting parallel methylation and genetic evolution. De-convolution reveal higher ratio of T regulatory cells (Tregs) versus CD8 + T cells in later-stage diseases, implying progressive immunosuppression with neoplastic progression. Furthermore, increased global hypomethylation is associated with higher mutation burden, copy number variation burden and AI burden as well as higher Treg/CD8 ratio, highlighting the potential impact of methylation on chromosomal instability, mutagenesis and tumor immune microenvironment during early carcinogenesis of lung adenocarcinomas.
Geminate labels programmed by two-tone microdroplets combining structural and fluorescent color
Authors: Qin Lang , Liu Xiaojun , He Kunyun , Yu Guodong , Yuan Hang , Xu Ming , Li Fuyou , Yu Yanlei 
Published: January 2021

AbstractCreating a security label that carries entirely distinct information in reflective and fluorescent states would enhance anti-counterfeiting levels to deter counterfeits ranging from currencies to pharmaceuticals, but has proven extremely challenging. Efforts to tune the reflection color of luminescent materials by modifying inherent chemical structures remain outweighed by substantial trade-offs in fluorescence properties, and vice versa, which destroys the information integrity of labels in either reflection or fluorescent color. Here, a strategy is reported to design geminate labels by programming fluorescent cholesteric liquid crystal microdroplets (two-tone inks), where the luminescent material is ‘coated’ with the structural color from helical superstructures. These structurally defined microdroplets fabricated by a capillary microfluidic technique contribute to different but intact messages of both reflective and fluorescent patterns in the geminate labels. Such two-tone inks have enormous potential to provide a platform for encryption and protection of valuable authentic information in anti-counterfeiting technology.
Cas9-AAV6 gene correction of beta-globin in autologous HSCs improves sickle cell disease erythropoiesis in mice
Authors: Wilkinson Adam C. , Dever Daniel P. , Baik Ron , Camarena Joab , Hsu Ian , Charlesworth Carsten T. , Morita Chika , Nakauchi Hiromitsu , Porteus Matthew H. 
Published: January 2021

AbstractCRISPR/Cas9-mediated beta-globin (HBB) gene correction of sickle cell disease (SCD) patient-derived hematopoietic stem cells (HSCs) in combination with autologous transplantation represents a recent paradigm in gene therapy. Although several Cas9-based HBB-correction approaches have been proposed, functional correction of in vivo erythropoiesis has not been investigated previously. Here, we use a humanized globin-cluster SCD mouse model to study Cas9-AAV6-mediated HBB-correction in functional HSCs within the context of autologous transplantation. We discover that long-term multipotent HSCs can be gene corrected ex vivo and stable hemoglobin-A production can be achieved in vivo from HBB-corrected HSCs following autologous transplantation. We observe a direct correlation between increased HBB-corrected myeloid chimerism and normalized in vivo red blood cell (RBC) features, but even low levels of chimerism resulted in robust hemoglobin-A levels. Moreover, this study offers a platform for gene editing of mouse HSCs for both basic and translational research.
Artificial intelligence in sepsis early prediction and diagnosis using unstructured data in healthcare
Authors: Goh Kim Huat , Wang Le , Yeow Adrian Yong Kwang , Poh Hermione , Li Ke , Yeow Joannas Jie Lin , Tan Gamaliel Yu Heng 
Published: January 2021

AbstractSepsis is a leading cause of death in hospitals. Early prediction and diagnosis of sepsis, which is critical in reducing mortality, is challenging as many of its signs and symptoms are similar to other less critical conditions. We develop an artificial intelligence algorithm, SERA algorithm, which uses both structured data and unstructured clinical notes to predict and diagnose sepsis. We test this algorithm with independent, clinical notes and achieve high predictive accuracy 12 hours before the onset of sepsis (AUC 0.94, sensitivity 0.87 and specificity 0.87). We compare the SERA algorithm against physician predictions and show the algorithm’s potential to increase the early detection of sepsis by up to 32% and reduce false positives by up to 17%. Mining unstructured clinical notes is shown to improve the algorithm’s accuracy compared to using only clinical measures for early warning 12 to 48 hours before the onset of sepsis.
Coherent characterisation of a single molecule in a photonic black box
Authors: Boissier Sebastien , Schofield Ross C. , Jin Lin , Ovvyan Anna , Nur Salahuddin , Koppens Frank H. L. , Toninelli Costanza , Pernice Wolfram H. P. , Major Kyle D. , Hinds E. A. , Clark Alex S. 
Published: January 2021

AbstractExtinction spectroscopy is a powerful tool for demonstrating the coupling of a single quantum emitter to a photonic structure. However, it can be challenging in all but the simplest of geometries to deduce an accurate value of the coupling efficiency from the measured spectrum. Here we develop a theoretical framework to deduce the coupling efficiency from the measured transmission and reflection spectra without precise knowledge of the photonic environment. We then consider the case of a waveguide interrupted by a transverse cut in which an emitter is placed. We apply that theory to a silicon nitride waveguide interrupted by a gap filled with anthracene that is doped with dibenzoterrylene molecules. We describe the fabrication of these devices, and experimentally characterise the waveguide coupling of a single molecule in the gap.
Bayesian data analysis reveals no preference for cardinal Tafel slopes in CO2 reduction electrocatalysis
Authors: Limaye Aditya M. , Zeng Joy S. , Willard Adam P. , Manthiram Karthish 
Published: January 2021

AbstractThe Tafel slope is a key parameter often quoted to characterize the efficacy of an electrochemical catalyst. In this paper, we develop a Bayesian data analysis approach to estimate the Tafel slope from experimentally-measured current-voltage data. Our approach obviates the human intervention required by current literature practice for Tafel estimation, and provides robust, distributional uncertainty estimates. Using synthetic data, we illustrate how data insufficiency can unknowingly influence current fitting approaches, and how our approach allays these concerns. We apply our approach to conduct a comprehensive re-analysis of data from the CO2reduction literature. This analysis reveals no systematic preference for Tafel slopes to cluster around certain "cardinal values” (e.g. 60 or 120 mV/decade). We hypothesize several plausible physical explanations for this observation, and discuss the implications of our finding for mechanistic analysis in electrochemical kinetic investigations.
Perception of a divergent family of phytocytokines by the Arabidopsis receptor kinase MIK2
Authors: Rhodes Jack , Yang Huanjie , Moussu Steven , Boutrot Freddy , Santiago Julia , Zipfel Cyril 
Published: January 2021

AbstractPlant genomes encode hundreds of receptor kinases and peptides, but the number of known plant receptor-ligand pairs is limited. We report that the Arabidopsis leucine-rich repeat receptor kinase LRR-RK MALE DISCOVERER 1-INTERACTING RECEPTOR LIKE KINASE 2 (MIK2) is the receptor for the SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) phytocytokines. MIK2 is necessary and sufficient for immune responses triggered by multiple SCOOP peptides, suggesting that MIK2 is the receptor for this divergent family of peptides. Accordingly, the SCOOP12 peptide directly binds MIK2 and triggers complex formation between MIK2 and the BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) co-receptor. MIK2 is required for resistance to the important root pathogen Fusarium oxysporum. Notably, we reveal that Fusarium proteomes encode SCOOP-like sequences, and corresponding synthetic peptides induce MIK2-dependent immune responses. These results suggest that MIK2 may recognise Fusarium-derived SCOOP-like sequences to induce immunity against Fusarium. The definition of SCOOPs as MIK2 ligands will help to unravel the multiple roles played by MIK2 during plant growth, development and stress responses.
Highly efficient photoelectric effect in halide perovskites for regenerative electron sources
Authors: Liu Fangze , Sidhik Siraj , Hoffbauer Mark A. , Lewis Sina , Neukirch Amanda J. , Pavlenko Vitaly , Tsai Hsinhan , Nie Wanyi , Even Jacky , Tretiak Sergei , Ajayan Pulickel M. , Kanatzidis Mercouri G. , Crochet Jared J. , Moody Nathan A. , Blancon Jean-Christophe , Mohite Aditya D. 
Published: January 2021

AbstractElectron sources are a critical component in a wide range of applications such as electron-beam accelerator facilities, photomultipliers, and image intensifiers for night vision. We report efficient, regenerative and low-cost electron sources based on solution-processed halide perovskites thin films when they are excited with light with energy equal to or above their bandgap. We measure a quantum efficiency up to 2.2% and a lifetime of more than 25 h. Importantly, even after degradation, the electron emission can be completely regenerated to its maximum efficiency by deposition of a monolayer of Cs. The electron emission from halide perovskites can be tuned over the visible and ultraviolet spectrum, and operates at vacuum levels with pressures at least two-orders higher than in state-of-the-art semiconductor electron sources.
NeissLock provides an inducible protein anhydride for covalent targeting of endogenous proteins
Authors: Scheu Arne H. A. , Lim Sheryl Y. T. , Metzner Felix J. , Mohammed Shabaz , Howarth Mark 
Published: January 2021

AbstractThe Neisseria meningitidisproteinFrpCcontains a self-processing module (SPM) undergoing autoproteolysis via an aspartic anhydride. Herein, we establish NeissLock, using a binding protein genetically fused to SPM. Upon calcium triggering of SPM, the anhydride at the C-terminus of the binding protein allows nucleophilic attack by its target protein, ligating the complex. We establish a computational tool to search the Protein Data Bank, assessing proximity of amines to C-termini. We optimize NeissLock using the Ornithine Decarboxylase/Antizyme complex. Various sites on the target (α-amine or ε-amines) react with the anhydride, but reaction is blocked if the partner does not dock. Ligation is efficient at pH 7.0, with half-time less than 2 min. We arm Transforming Growth Factor-α with SPM, enabling specific covalent coupling to Epidermal Growth Factor Receptor at the cell-surface. NeissLock harnesses distinctive protein chemistry for high-yield covalent targeting of endogenous proteins, advancing the possibilities for molecular engineering.
Role of an ancient light-harvesting protein of PSI in light absorption and photoprotection
Authors: Lu Yandu , Gan Qinhua , Iwai Masakazu , Alboresi Alessandro , Burlacot Adrien , Dautermann Oliver , Takahashi Hiroko , Crisanto Thien , Peltier Gilles , Morosinotto Tomas , Melis Anastasios , Niyogi Krishna K. 
Published: January 2021

AbstractDiverse algae of the red lineage possess chlorophyll a-binding proteins termed LHCR, comprising the PSI light-harvesting system, which represent an ancient antenna form that evolved in red algae and was acquired through secondary endosymbiosis. However, the function and regulation of LHCR complexes remain obscure. Here we describe isolation of a Nannochloropsis oceanica LHCR mutant, named hlr1, which exhibits a greater tolerance to high-light (HL) stress compared to the wild type. We show that increased tolerance to HL of the mutant can be attributed to alterations in PSI, making it less prone to ROS production, thereby limiting oxidative damage and favoring growth in HL. HLR1 deficiency attenuates PSI light-harvesting capacity and growth of the mutant under light-limiting conditions. We conclude that HLR1, a member of a conserved and broadly distributed clade of LHCR proteins, plays a pivotal role in a dynamic balancing act between photoprotection and efficient light harvesting for photosynthesis.
Backbone-independent NMR resonance assignments of methyl probes in large proteins
Authors: Nerli Santrupti , De Paula Viviane S. , McShan Andrew C. , Sgourakis Nikolaos G. 
Published: January 2021

AbstractMethyl-specific isotope labeling is a powerful tool to study the structure, dynamics and interactions of large proteins and protein complexes by solution-state NMR. However, widespread applications of this methodology have been limited by challenges in obtaining confident resonance assignments. Here, we present Methyl Assignments Using Satisfiability (MAUS), leveraging Nuclear Overhauser Effect cross-peak data, peak residue type classification and a known 3D structure or structural model to provide robust resonance assignments consistent with all the experimental inputs. Using data recorded for targets with known assignments in the 10–45 kDa size range, MAUS outperforms existing methods by up to 25,000 times in speed while maintaining 100% accuracy. We derive de novo assignments for multiple Cas9 nuclease domains, demonstrating that the methyl resonances of multi-domain proteins can be assigned accurately in a matter of days, while reducing biases introduced by manual pre-processing of the raw NOE data. MAUS is available through an online web-server.
Posttranslational chemical installation of azoles into translated peptides
Authors: Tsutsumi Haruka , Kuroda Tomohiro , Kimura Hiroyuki , Goto Yuki , Suga Hiroaki 
Published: January 2021

AbstractAzoles are five-membered heterocycles often found in the backbones of peptidic natural products and synthetic peptidomimetics. Here, we report a method of ribosomal synthesis of azole-containing peptides involving specific ribosomal incorporation of a bromovinylglycine derivative into the nascent peptide chain and its chemoselective conversion to a unique azole structure. The chemoselective conversion was achieved by posttranslational dehydrobromination of the bromovinyl group and isomerization in aqueous media under fairly mild conditions. This method enables us to install exotic azole groups, oxazole and thiazole, at designated positions in the peptide chain with both linear and macrocyclic scaffolds and thereby expand the repertoire of building blocks in the mRNA-templated synthesis of designer peptides.
Gut bacteria are essential for normal cuticle development in herbivorous turtle ants
Authors: Duplais Christophe , Sarou-Kanian Vincent , Massiot Dominique , Hassan Alia , Perrone Barbara , Estevez Yannick , Wertz John T. , Martineau Estelle , Farjon Jonathan , Giraudeau Patrick , Moreau Corrie S. 
Published: January 2021

AbstractAcross the evolutionary history of insects, the shift from nitrogen-rich carnivore/omnivore diets to nitrogen-poor herbivorous diets was made possible through symbiosis with microbes. The herbivorous turtle ants Cephalotes possess a conserved gut microbiome which enriches the nutrient composition by recycling nitrogen-rich metabolic waste to increase the production of amino acids. This enrichment is assumed to benefit the host, but we do not know to what extent. To gain insights into nitrogen assimilation in the ant cuticle we use gut bacterial manipulation, 15N isotopic enrichment, isotope-ratio mass spectrometry, and 15N nuclear magnetic resonance spectroscopy to demonstrate that gut bacteria contribute to the formation of proteins, catecholamine cross-linkers, and chitin in the cuticle. This study identifies the cuticular components which are nitrogen-enriched by gut bacteria, highlighting the role of symbionts in insect evolution, and provides a framework for understanding the nitrogen flow from nutrients through bacteria into the insect cuticle.
Towards fully automated GW band structure calculations: What we can learn from 60.000 self-energy evaluations
Authors: Rasmussen Asbjørn , Deilmann Thorsten , Thygesen Kristian S. 
Published: January 2021

AbstractWe analyze a data set comprising 370 GW band structures of two-dimensional (2D) materials covering 14 different crystal structures and 52 chemical elements. The band structures contain a total of 61716 quasiparticle (QP) energies obtained from plane-wave-based one-shot G0W0@PBE calculations with full frequency integration. We investigate the distribution of key quantities, like the QP self-energy corrections and QP weights, and explore their dependence on chemical composition and magnetic state. The linear QP approximation is identified as a significant error source and we propose schemes for controlling and drastically reducing this error at low computational cost. We analyze the reliability of the 1/N basis set extrapolation and find that is well-founded with a narrow distribution of coefficients of determination (r2) peaked very close to 1. Finally, we explore the accuracy of the scissors operator approximation and conclude that its validity is very limited. Our work represents a step towards the development of automatized workflows for high-throughput G0W0 band structure calculations for solids.
Leakage reduction in fast superconducting qubit gates via optimal control
Authors: Werninghaus M. , Egger D. J. , Roy F. , Machnes S. , Wilhelm F. K. , Filipp S. 
Published: January 2021

AbstractReaching high-speed, high-fidelity qubit operations requires precise control over the shape of the underlying pulses. For weakly anharmonic systems, such as superconducting transmon qubits, short gates lead to leakage to states outside of the computational subspace. Control pulses designed with open-loop optimal control may reduce such leakage. However, model inaccuracies can severely limit the usability of such pulses. We implemented a closed-loop optimization that simultaneously adapts all control parameters based on measurements of a cost function built from Clifford gates. We directly optimize the amplitude and phase of each sample point of the digitized control pulse. We thereby fully exploit the capabilities of the pulse generation electronics and create a 4.16 ns single-qubit pulse with 99.76 % fidelity and 0.044 % leakage. This is a sevenfold reduction of the leakage rate and a threefold reduction in standard errors of the best DRAG pulse we have calibrated at such short durations on the same system.
Optimizing a polynomial function on a quantum processor
Authors: Li Keren , Wei Shijie , Gao Pan , Zhang Feihao , Zhou Zengrong , Xin Tao , Wang Xiaoting , Rebentrost Patrick , Long Guilu 
Published: January 2021

AbstractThe gradient descent method is central to numerical optimization and is the key ingredient in many machine learning algorithms. It promises to find a local minimum of a function by iteratively moving along the direction of the steepest descent. Since for high-dimensional problems the required computational resources can be prohibitive, it is desirable to investigate quantum versions of the gradient descent, such as the recently proposed (Rebentrost et al.1). Here, we develop this protocol and implement it on a quantum processor with limited resources. A prototypical experiment is shown with a four-qubit nuclear magnetic resonance quantum processor, which demonstrates the iterative optimization process. Experimentally, the final point converged to the local minimum with a fidelity >94%, quantified via full-state tomography. Moreover, our method can be employed to a multidimensional scaling problem, showing the potential to outperform its classical counterparts. Considering the ongoing efforts in quantum information and data science, our work may provide a faster approach to solving high-dimensional optimization problems and a subroutine for future practical quantum computers.