bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Mutations 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

The 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

Creating 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

CRISPR/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

Sepsis 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

Extinction 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

The 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

Plant 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

Electron 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

The 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

Diverse 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

Methyl-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

Azoles 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

Across 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.
Author Correction: Uncoupling of invasive bacterial mucosal immunogenicity from pathogenicity
Authors: Pfister Simona P. , Schären Olivier P. , Beldi Luca , Printz Andrea , Notter Matheus D. , Mukherjee Mohana , Li Hai , Limenitakis Julien P. , Werren Joel P. , Tandon Disha , Cuenca Miguelangel , Hagemann Stefanie , Uster Stephanie S. , Terrazos Miguel A. , de Agüero Mercedes Gomez , Schürch Christian M. , Coelho Fernanda M. , Curtiss Roy , Slack Emma , Balmer Maria L. , Hapfelmeier Siegfried
Published: January 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21096-5.
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

We 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

Reaching 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

The 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.
LC–MS based case-by-case analysis of the impact of acidic and basic charge variants of bevacizumab on stability and biological activity
Authors: Singh Sumit Kumar , Kumar Deepak , Malani Himanshu , Rathore Anurag S.
Published: January 2021

The present study investigates the impact of charge variants on bevacizumab's structure, stability, and biological activity. Five basic and one acidic charge variants were separated using semi-preparative cation exchange chromatography using linear pH gradient elution with purity > 85%. Based on the commercial biosimilar product's composition, two basic variants, one acidic and the main bevacizumab product, were chosen for further investigation. Intact mass analysis and tryptic peptide mapping established the basic variants' identity as those originating from an incomplete clipping of either one or both C-terminal lysine residues in the heavy chain of bevacizumab. Based on peptide mapping data, the acidic variant formation was attributed to deamidation of asparagine residue (N84), oxidation of M258, and preservation of C-terminal lysine residue, located on the heavy chain of bevacizumab. None of the observed charge heterogeneities in bevacizumab were due to differences in glycosylation among the variants. The basic (lysine) variants exhibited similar structural, functional, and stability profiles as the bevacizumab main product. But it was also noted that both the variants did not improve bevacizumab's therapeutic utility when pooled in different proportions with the main product. The acidic variant was found to have an equivalent secondary structure with subtle differences in the tertiary structure. The conformational difference also translated into a ~ 62% decrease in biological activity. Based on these data, it can be concluded that different charge variants behave differently with respect to their structure and bioactivity. Hence, biopharmaceutical manufacturers need to incorporate this understanding into their process and product development guidelines to maintain consistency in product quality.
First instar larvae of endemic Australian Miltogramminae (Diptera: Sarcophagidae)
Authors: Szpila Krzysztof , Walczak Kinga , Johnston Nikolas P. , Pape Thomas , Wallman James F.
Published: January 2021

The first instar larva of a species of the Australian endemic genus Aenigmetopia Malloch is described for the first time, along with the first instar larvae of three other Australian species representing the genera Amobia Robineau-Desvoidy and Protomiltogramma Townsend. Larval morphology was analysed using a combination of light microscopy, confocal laser scanning microscopy and scanning electron microscopy. The following morphological structures are documented: pseudocephalon, antennal complex, maxillary palpus, facial mask, modifications of thoracic and abdominal segments, anal region, spiracular field, posterior spiracles and details of the cephaloskeleton. Substantial morphological differences are observed between the three genera, most notably in the labrum and mouthhooks of the cephaloskeleton, sensory organs of the pseudocephalon, spinulation, sculpture of the integument and form of the spiracular field. The first instar larval morphology of Aenigmetopia amissa Johnston, Wallman, Szpila & Pape corroborates the close phylogenetic affinity of Aenigmetopia Malloch with Metopia Meigen, inferred from recent molecular analysis. The larval morphology of Amobia auriceps (Baranov), Protomiltogramma cincta Townsend and Protomiltogramma plebeia Malloch is mostly congruent with the morphology of Palaearctic representatives of both genera.
Head motion classification using thread-based sensor and machine learning algorithm
Authors: Jiang Yiwen , Sadeqi Aydin , Miller Eric L. , Sonkusale Sameer
Published: January 2021

Human machine interfaces that can track head motion will result in advances in physical rehabilitation, improved augmented reality/virtual reality systems, and aid in the study of human behavior. This paper presents a head position monitoring and classification system using thin flexible strain sensing threads placed on the neck of an individual. A wireless circuit module consisting of impedance readout circuitry and a Bluetooth module records and transmits strain information to a computer. A data processing algorithm for motion recognition provides near real-time quantification of head position. Incoming data is filtered, normalized and divided into data segments. A set of features is extracted from each data segment and employed as input to nine classifiers including Support Vector Machine, Naive Bayes and KNN for position prediction. A testing accuracy of around 92% was achieved for a set of nine head orientations. Results indicate that this human machine interface platform is accurate, flexible, easy to use, and cost effective.
Post-collisional mantle delamination in the Dinarides implied from staircases of Oligo-Miocene uplifted marine terraces
Authors: Balling Philipp , Grützner Christoph , Tomljenović Bruno , Spakman Wim , Ustaszewski Kamil
Published: January 2021

The Dinarides fold-thrust belt on the Balkan Peninsula resulted from convergence between the Adriatic and Eurasian plates since Mid-Jurassic times. Under the Dinarides, S-wave receiver functions, P-wave tomographic models, and shear-wave splitting data show anomalously thin lithosphere overlying a short down-flexed slab geometry. This geometry suggests a delamination of Adriatic lithosphere. Here, we link the evolution of this continental convergence system to hitherto unreported sets of extensively uplifted Oligocene–Miocene (28–17 Ma) marine terraces preserved at elevations of up to 600 m along the Dinaric coastal range. River incision on either side of the Mediterranean-Black Sea drainage divide is comparable to the amounts of terrace uplift. The preservation of the uplifted terraces implies that the most External Dinarides did not experience substantial deformation other than surface uplift in the Neogene. These observations and the contemporaneous emplacement of igneous rocks (33–22 Ma) in the internal Dinarides suggest that the Oligo-Miocene orogen-wide uplift was driven by post-break-off delamination of the Adriatic lithospheric mantle, this was followed by isostatic readjustment of the remaining crust. Our study details how lithospheric delamination exerts an important control on crustal deformation and that its crustal signature and geomorphic imprint can be preserved for millions of years.
Greenhouse gas emissions from the water–air interface of a grassland river: a case study of the Xilin River
Authors: Hao Xue , Ruihong Yu , Zhuangzhuang Zhang , Zhen Qi , Xixi Lu , Tingxi Liu , Ruizhong Gao
Published: January 2021

Greenhouse gas (GHG) emissions from rivers and lakes have been shown to significantly contribute to global carbon and nitrogen cycling. In spatiotemporal-variable and human-impacted rivers in the grassland region, simultaneous carbon dioxide, methane and nitrous oxide emissions and their relationships under the different land use types are poorly documented. This research estimated greenhouse gas (CO2, CH4, N2O) emissions in the Xilin River of Inner Mongolia of China using direct measurements from 18 field campaigns under seven land use type (such as swamp, sand land, grassland, pond, reservoir, lake, waste water) conducted in 2018. The results showed that CO2 emissions were higher in June and August, mainly affected by pH and DO. Emissions of CH4 and N2O were higher in October, which were influenced by TN and TP. According to global warming potential, CO2 emissions accounted for 63.35% of the three GHG emissions, and CH4 and N2O emissions accounted for 35.98% and 0.66% in the Xilin river, respectively. Under the influence of different degrees of human-impact, the amount of CO2 emissions in the sand land type was very high, however, CH4 emissions and N2O emissions were very high in the artificial pond and the wastewater, respectively. For natural river, the greenhouse gas emissions from the reservoir and sand land were both low. The Xilin river was observed to be a source of carbon dioxide and methane, and the lake was a sink for nitrous oxide.
Continuous learning and inference of individual probability of SARS-CoV-2 infection based on interaction data
Authors: Liu Shangching , Liu Koyun , Chiang Hwaihai , Zhang Jianwei , Chang Tsungyao
Published: January 2021

This study presents a new approach to determine the likelihood of asymptomatic carriers of the SARS-CoV-2 virus by using interaction-based continuous learning and inference of individual probability (CLIIP) for contagious ranking. This approach is developed based on an individual directed graph (IDG), using multi-layer bidirectional path tracking and inference searching. The IDG is determined by the appearance timeline and spatial data that can adapt over time. Additionally, the approach takes into consideration the incubation period and several features that can represent real-world circumstances, such as the number of asymptomatic carriers present. After each update of confirmed cases, the model collects the interaction features and infers the individual person’s probability of getting infected using the status of the surrounding people. The CLIIP approach is validated using the individualized bidirectional SEIR model to simulate the contagion process. Compared to traditional contact tracing methods, our approach significantly reduces the screening and quarantine required to search for the potential asymptomatic virus carriers by as much as 94%.
Comparative gene expression analysis reveals that multiple mechanisms regulate the weeping trait in Prunus mume
Authors: Li Lulu , Zhang Yichi , Zheng Tangchun , Zhuo Xiaokang , Li Ping , Qiu Like , Liu Weichao , Wang Jia , Cheng Tangren , Zhang Qixiang
Published: January 2021

Prunus mume (also known as Mei) is an important ornamental plant that is popular with Asians. The weeping trait in P. mume has attracted the attention of researchers for its high ornamental value. However, the formation of the weeping trait of woody plants is a complex process and the molecular basis of weeping stem development is unclear. Here, the morphological and histochemical characteristics and transcriptome profiles of upright and weeping stems from P. mume were studied. Significant alterations in the histochemical characteristics of upright and weeping stems were observed, and the absence of phloem fibres and less xylem in weeping stems might be responsible for their inability to resist gravity and to grow downward. Transcriptome analysis showed that differentially expressed genes (DEGs) were enriched in phenylpropanoid biosynthesis and phytohormone signal transduction pathways. To investigate the differential responses to hormones, upright and weeping stems were treated with IAA (auxin) and GA3 (gibberellin A3), respectively, and the results revealed that weeping stems had a weaker IAA response ability and reduced upward bending angles than upright stems. On the contrary, weeping stems had increased upward bending angles than upright stems with GA3 treatment. Compared to upright stems, interestingly, DEGs associated with diterpenoid biosynthesis and phenylpropanoid biosynthesis were significantly enriched after being treated with IAA, and expression levels of genes associated with phenylpropanoid biosynthesis, ABC transporters, glycosylphosphatidylinositol (GPI)—anchor biosynthesis were altered after being treated with GA3 in weeping stems. Those results reveal that multiple molecular mechanisms regulate the formation of weeping trait in P. mume, which lays a theoretical foundation for the cultivation of new varieties.
Simulating self-learning in photorefractive optical reservoir computers
Authors: Laporte Floris , Dambre Joni , Bienstman Peter
Published: January 2021

Photorefractive materials exhibit an interesting plasticity under the influence of an optical field. By extending the finite-difference time-domain method to include the photorefractive effect, we explore how this property can be exploited in the context of neuromorphic computing for telecom applications. By first priming the photorefractive material with a random bit stream, the material reorganizes itself to better recognize simple patterns in the stream. We demonstrate this by simulating a typical reservoir computing setup, which gets a significant performance boost on performing the XOR on two consecutive bits in the stream after this initial priming step.
Evaluation of an eye tracking setup for studying visual attention in face-to-face conversations
Authors: Vehlen Antonia , Spenthof Ines , Tönsing Daniel , Heinrichs Markus , Domes Gregor
Published: January 2021

Many eye tracking studies use facial stimuli presented on a display to investigate attentional processing of social stimuli. To introduce a more realistic approach that allows interaction between two real people, we evaluated a new eye tracking setup in three independent studies in terms of data quality, short-term reliability and feasibility. Study 1 measured the robustness, precision and accuracy for calibration stimuli compared to a classical display-based setup. Study 2 used the identical measures with an independent study sample to compare the data quality for a photograph of a face (2D) and the face of the real person (3D). Study 3 evaluated data quality over the course of a real face-to-face conversation and examined the gaze behavior on the facial features of the conversation partner. Study 1 provides evidence that quality indices for the scene-based setup were comparable to those of a classical display-based setup. Average accuracy was better than 0.4° visual angle. Study 2 demonstrates that eye tracking quality is sufficient for 3D stimuli and robust against short interruptions without re-calibration. Study 3 confirms the long-term stability of tracking accuracy during a face-to-face interaction and demonstrates typical gaze patterns for facial features. Thus, the eye tracking setup presented here seems feasible for studying gaze behavior in dyadic face-to-face interactions. Eye tracking data obtained with this setup achieves an accuracy that is sufficient for investigating behavior such as eye contact in social interactions in a range of populations including clinical conditions, such as autism spectrum and social phobia.
Comparison of DNA sequencing and morphological identification techniques to characterize environmental fungal communities
Authors: Shinohara Naohide , Woo Cheolwoon , Yamamoto Naomichi , Hashimoto Kazuhiro , Yoshida-Ohuchi Hiroko , Kawakami Yuji
Published: January 2021

Culture-independent DNA sequencing of fungal internal transcribed spacer 2 (ITS2) region was compared to a culture-dependent morphological identification technique to characterize house dust-borne fungal communities. The abundant genera were Aspergillus, Wallemia, Cladosporium, and Penicillium. Statistically significant between-method correlations were observed for Wallemia and Cladosporium (Spearman’s ρ = 0.75 and 0.72, respectively; p < 0.001). Penicillium tended to be detected with much higher (averaged 26-times) relative abundances by the culture-based method than by the DNA-based method, although statistically significant inter-method correlation was observed with Spearman’s ρ = 0.61 (p = 0.002). Large DNA sequencing-based relative abundances observed for Alternaria and Aureobasidium were likely due to multicellularity of their spores with large number of per-spore ITS2 copies. The failure of the culture-based method in detectiing Toxicocladosporium, Verrucocladosporium, and Sterigmatomyces was likely due to their fastidiousness growth on our nutrient medium. Comparing between the two different techniques clarified the causes of biases in identifying environmental fungal communities, which should be amended and/or taken into consideration when the methods are used for future fungal ecological studies.
Peat deposits store more carbon than trees in forested peatlands of the boreal biome
Authors: Beaulne Joannie , Garneau Michelle , Magnan Gabriel , Boucher Étienne
Published: January 2021

Peatlands are significant carbon (C) stores, playing a key role in nature-based climate change mitigation. While the effectiveness of non-forested peatlands as C reservoirs is increasingly recognized, the C sequestration function of forested peatlands remains poorly documented, despite their widespread distribution. Here, we evaluate the C sequestration potential of pristine boreal forested peatlands over both recent and millennial timescales. C stock estimates reveal that most of the carbon stored in these ecosystems is found in organic horizons (22.6–66.0 kg m−2), whereas tree C mass (2.8–5.7 kg m−2) decreases with thickening peat. For the first time, we compare the boreal C storage capacities of peat layers and tree biomass on the same timescale, showing that organic horizons (11.0–12.6 kg m−2) can store more carbon than tree aboveground and belowground biomass (2.8–5.7 kg m−2) even over a short time period (last 200 years). We also show that forested peatlands have similar recent rates of C accumulation to boreal non-forested peatlands but lower long-term rates, suggesting higher decay and more important peat layer combustion during fire events. Our findings highlight the significance of forested peatlands for C sequestration and suggest that greater consideration should be given to peat C stores in national greenhouse gas inventories and conservation policies.
Macaque monkeys learn and perform a non-match-to-goal task using an automated home cage training procedure
Authors: Sacchetti Stefano , Ceccarelli Francesco , Ferrucci Lorenzo , Benozzo Danilo , Brunamonti Emiliano , Nougaret Simon , Genovesio Aldo
Published: January 2021

In neurophysiology, nonhuman primates represent an important model for studying the brain. Typically, monkeys are moved from their home cage to an experimental room daily, where they sit in a primate chair and interact with electronic devices. Refining this procedure would make the researchers’ work easier and improve the animals’ welfare. To address this issue, we used home-cage training to train two macaque monkeys in a non-match-to-goal task, where each trial required a switch from the choice made in the previous trial to obtain a reward. The monkeys were tested in two versions of the task, one in which they acted as the agent in every trial and one in which some trials were completed by a “ghost agent”. We evaluated their involvement in terms of their performance and their interaction with the apparatus. Both monkeys were able to maintain a constant involvement in the task with good, stable performance within sessions in both versions of the task. Our study confirms the feasibility of home-cage training and demonstrates that even with challenging tasks, monkeys can complete a large number of trials at a high performance level, which is a prerequisite for electrophysiological studies of monkey behavior.
Prenatal disorders and congenital Zika syndrome in squirrel monkeys
Authors: Imbeloni Aline Amaral , de Alcantara Bianca Nascimento , Coutinho Leandro Nassar , de Azevedo Scalercio Sarah Raphaella Rocha , Carneiro Liliane Almeida , Oliveira Karol Guimarães , Filho Arnaldo Jorge Martins , de Brito Simith Durans Darlene , da Silva Wellington Bandeira , Nunes Bruno Tardelli Diniz , Casseb Livia Medeiros Neves , Chiang Jannifer Oliveira , de Carvalho Carlos Alberto Marques , Machado Mariana Borges , Quaresma Juarez Antônio Simões , de Almeida Medeiros Daniele Barbosa , da Costa Vasconcelos Pedro Fernando
Published: January 2021

During the Zika virus (ZIKV) outbreak in Brazil (2015–2016), the clinical manifestations associated with its infection were complex and included miscarriage and congenital malformations, not previously described. In this study, we evaluated the prenatal conditions of pregnant female squirrel monkeys (Saimiri collinsi) infected during different gestational thirds (GTs) and assessed all clinical aspects, diagnostic imaging, viremia and the immune response. In our study, 75% of the infected animals in the 1st GT group had significant clinical manifestations, such as miscarriage and prolonged viremia associated with a late immune response. Consequently, their neonates showed fetal neuropathology, such as cerebral hemorrhage, lissencephaly or malformations of the brain grooves, ventriculomegaly, and craniofacial malformations. Thus, our study demonstrated the relevance of pregnant squirrel monkeys as a model for the study of ZIKV infection in neonates due to the broad clinical manifestations presented, including the typical congenital Zika syndrome manifestations described in humans.
High level of pre-treatment C-reactive protein to albumin ratio predicts inferior prognosis in diffuse large B-cell lymphoma
Authors: Jung Jongheon , Lee Hyewon , Heo Ja Yoon , Chang Myung Hee , Lee Eunyoung , Park Weon Seo , Park Ju-Hyun , Eom Hyeon-Seok
Published: January 2021

The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p < 0.001), 3-year overall survival (OS) (68.3% vs. 96.2%; p < 0.0001), and 3-year progression-free survival (PFS) (53.5% vs. 88.0%; p < 0.0001). After adjusting for the International Prognostic Index components, a high CAR value independently predicted poor OS (HR: 6.02, 95% CI 1.19–30.38; p = 0.030) and PFS (HR: 3.62, 95% CI 1.40–9.36; p = 0.008). In an independent validation cohort (n = 50), patients with CAR > 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases.
Transcriptome analysis reveals the long intergenic noncoding RNAs contributed to skeletal muscle differences between Yorkshire and Tibetan pig
Authors: Huang Ziying , Li Qianqian , Li Mengxun , Li Changchun
Published: January 2021

The difference between the skeletal muscle growth rates of Western and domestic breeds is remarkable, but the potential regulatory mechanism involved is still unclear. Numerous studies have pointed out that long intergenic noncoding RNA (lincRNA) plays a key role in skeletal muscle development. This study used published Yorkshire (LW) and Tibetan pig (TP) transcriptome data to explore the possible role of lincRNA in the difference in skeletal muscle development between the two breeds. 138 differentially expressed lincRNAs (DELs) were obtained between the two breeds, and their potential target genes (PTGs) were predicted. The results of GO and KEGG analysis revealed that PTGs are involved in multiple biological processes and pathways related to muscle development. The quantitative trait loci (QTLs) of DELs were predicted, and the results showed that most QTLs are related to muscle development. Finally, we constructed a co-expression network between muscle development related PTGs (MDRPTGs) and their corresponding DELs on the basis of their expression levels. The expression of DELs was significantly correlated with the corresponding MDRPTGs. Also, multiple MDRPTGs are involved in the key regulatory pathway of muscle fiber hypertrophy, which is the IGF-1-AKT-mTOR pathway. In summary, multiple lincRNAs that may cause differences in skeletal muscle development between the two breeds were identified, and their possible regulatory roles were explored. The findings of this study may provide a valuable reference for further research on the role of lincRNA in skeletal muscle development.