bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-equilibrium signal integration in hydrogels
Authors: Korevaar Peter A. , Kaplan C. Nadir , Grinthal Alison , Rust Reanne M. , Aizenberg Joanna
Published: January 2020

Materials that perform complex chemical signal processing are ubiquitous in living systems. Their synthetic analogs would transform developments in biomedicine, catalysis, and many other areas. By drawing inspiration from biological signaling dynamics, we show how simple hydrogels have a previously untapped capacity for non-equilibrium chemical signal processing and integration. Using a common polyacrylic acid hydrogel, with divalent cations and acid as representative stimuli, we demonstrate the emergence of non-monotonic osmosis-driven spikes and waves of expansion/contraction, as well as traveling color waves. These distinct responses emerge from different combinations of rates and sequences of arriving stimuli. A non-equilibrium continuum theory we developed quantitatively captures the non-monotonic osmosis-driven deformation waves and determines the onset of their emergence in terms of the input parameters. These results suggest that simple hydrogels, already built into numerous systems, have a much larger sensing space than currently employed.
Time-of-flight resolved light field fluctuations reveal deep human tissue physiology
Authors: Kholiqov Oybek , Zhou Wenjun , Zhang Tingwei , Du Le V. N. , Srinivasan Vivek J.
Published: January 2020

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.
The SUSTech-SYSU dataset for automatically segmenting and classifying corneal ulcers
Authors: Deng Lijie , Lyu Junyan , Huang Haixiang , Deng Yuqing , Yuan Jin , Tang Xiaoying
Published: January 2020

Corneal ulcer is a common ophthalmic symptom. Segmentation algorithms are needed to identify and quantify corneal ulcers from ocular staining images. Developments of such algorithms have been obstructed by a lack of high quality datasets (the ocular staining images and the corresponding gold-standard ulcer segmentation labels), especially for supervised learning based segmentation algorithms. In such context, we prepare a dataset containing 712 ocular staining images and the associated segmentation labels of flaky corneal ulcers. In addition to segmentation labels for flaky corneal ulcers, we also provide each image with three-fold class labels: firstly, each image has a label in terms of its general ulcer pattern; secondly, each image has a label in terms of its specific ulcer pattern; thirdly, each image has a label indicating its ulcer severity degree. This dataset not only provides an excellent opportunity for investigating the accuracy and reliability of different segmentation and classification algorithms for corneal ulcers, but also advances the development of new supervised learning based algorithms especially those in the deep learning framework.
Seasonal epiphytic microbial dynamics on grapevine leaves under biocontrol and copper fungicide treatments
Authors: Gobbi Alex , Kyrkou Ifigeneia , Filippi Elisa , Ellegaard-Jensen Lea , Hansen Lars Hestbjerg
Published: January 2020

Winemakers have long used copper as a conventional fungicide treatment on grapevine and only recently, the use of biocontrol agents depicted a promising alternative. Most of the studies that investigate the impact of fungicide treatments, focus on specific pathogenic microbes. In the present work instead, a field experiment conducted in South Africa shows the seasonal microbial change occurring on grapevine leaves, periodically treated with two different fungicide treatments: copper sulphate and Lactobacillus plantarum MW-1. In this work, NGS data were combined with strain-specific and community qPCRs to reveal the shift of the microbial communities throughout the growing season and highlight the impact of fungicides on the microbiota. Only the family of Lactobacillaceae systematically changed between treatments, while the bacterial community remained relatively stable over time. MW-1 was exclusively detected on biocontrol-sprayed leaves. Conversely, the fungal community was largely shaped by sampling time, underlining the succession of different dominant taxa over the months. Between treatments, only a few fungal taxa appeared to change significantly and the fungal load was also comparable. Monitoring the dynamics of the microbial community under different fungicide treatments may advise the best timing to apply treatments to the plants, toward the realization of more sustainable agricultural practices.
Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities
Authors: Song Zifeng , Pearce Martin C. , Jiang Yuan , Yang Liping , Goodall Cheri , Miranda Cristobal L. , Milovancev Milan , Bracha Shay , Kolluri Siva K. , Maier Claudia S.
Published: January 2020

Osteosarcoma (OS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. The proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined. To link metastatic propensity to a hypoxia-induced proteotype, we compared the protein profiles of two isogenic canine OS cell lines, POS (low metastatic) and HMPOS (highly metastatic), under normoxia and hypoxia. Label-free shotgun proteomics was applied to comprehensively characterize the hypoxia-responsive proteome profiles in the OS cell phenotypes. Hypothesis-driven parallel reaction monitoring was used to validate the differential proteins observed in the shotgun data and to monitor proteins of which we expected to exhibit hypoxia responsiveness, but which were absent in the label-free shotgun data. We established a “distance” score (|zHMPOS − zPOS|), and “sensitivity” score (|zHypoxia − zNormoxia) to quantitatively evaluate the proteome shifts exhibited by OS cells in response to hypoxia. Evaluation of the sensitivity scores for the proteome shifts observed and principal component analysis of the hypoxia-responsive proteins indicated that both cell types acquire a proteome that supports a Warburg phenotype with enhanced cell migration and proliferation characteristics. Cell migration and glucose uptake assays combined with protein function inhibitor studies provided further support that hypoxia-driven adaption of pathways associated with glycolytic metabolism, collagen biosynthesis and remodeling, redox regulation and immunomodulatory proteins typify a proteotype associated with an aggressive cancer cell phenotype. Our findings further suggest that proteins involved in collagen remodeling and immune editing may warrant further evaluation as potential targets for anti-metastatic treatment strategies in osteosarcoma.
Tempo-spectral multiplexing in flow cytometry with lifetime detection using QD-encoded polymer beads
Authors: Kage Daniel , Hoffmann Katrin , Nifontova Galina , Krivenkov Victor , Sukhanova Alyona , Nabiev Igor , Resch-Genger Ute
Published: January 2020

Semiconductor quantum dots (QDs) embedded into polymer microbeads are known to be very attractive emitters for spectral multiplexing and colour encoding. Their luminescence lifetimes or decay kinetics have been, however, rarely exploited as encoding parameter, although they cover time ranges which are not easily accessible with other luminophores. We demonstrate here the potential of QDs made from II/VI semiconductors with luminescence lifetimes of several 10 ns to expand the lifetime range of organic encoding luminophores in multiplexing applications using time-resolved flow cytometry (LT-FCM). For this purpose, two different types of QD-loaded beads were prepared and characterized by photoluminescence measurements on the ensemble level and by single-particle confocal laser scanning microscopy. Subsequently, these lifetime-encoded microbeads were combined with dye-encoded microparticles in systematic studies to demonstrate the potential of these QDs to increase the number of lifetime codes for lifetime multiplexing and combined multiplexing in the time and colour domain (tempo-spectral multiplexing). These studies were done with a recently developed novel luminescence lifetime flow cytometer (LT-FCM setup) operating in the time-domain, that presents an alternative to reports on phase-sensitive lifetime detection in flow cytometry.
The dynamic response of the Arabidopsis root metabolome to auxin and ethylene is not predicted by changes in the transcriptome
Authors: Hildreth Sherry B. , Foley Evan E. , Muday Gloria K. , Helm Richard F. , Winkel Brenda S. J.
Published: January 2020

While the effects of phytohormones on plant gene expression have been well characterized, comparatively little is known about how hormones influence metabolite profiles. This study examined the effects of elevated auxin and ethylene on the metabolome of Arabidopsis roots using a high-resolution 24 h time course, conducted in parallel to time-matched transcriptomic analyses. Mass spectrometry using orthogonal UPLC separation strategies (reversed phase and HILIC) in both positive and negative ionization modes was used to maximize identification of metabolites with altered levels. The findings show that the root metabolome responds rapidly to hormone stimulus and that compounds belonging to the same class of metabolites exhibit similar changes. The responses were dominated by changes in phenylpropanoid, glucosinolate, and fatty acid metabolism, although the nature and timing of the response was unique for each hormone. These alterations in the metabolome were not directly predicted by the corresponding transcriptome data, suggesting that post-transcriptional events such as changes in enzyme activity and/or transport processes drove the observed changes in the metabolome. These findings underscore the need to better understand the biochemical mechanisms underlying the temporal reconfiguration of plant metabolism, especially in relation to the hormone-metabolome interface and its subsequent physiological and morphological effects.
Immune gene signatures for predicting durable clinical benefit of anti-PD-1 immunotherapy in patients with non-small cell lung cancer
Authors: Hwang Sohyun , Kwon Ah-Young , Jeong Ju-Yeon , Kim Sewha , Kang Haeyoun , Park Joonsuk , Kim Joo-Hang , Han Ok Jin , Lim Sun Min , An Hee Jung
Published: January 2020

Immune checkpoint blockade is promising for treating non-small-cell lung cancer (NSCLC). We used multipanel markers to predict the response to immune checkpoint inhibitors (ICIs) by characterizing gene expression signatures or individual genes in patients who showed durable clinical benefit to ICIs. Twenty-one patients with NSCLC treated with single-agent anti-programmed cell death protein (PD)-1 antibody were analyzed and their clinicopathological characteristics and response to ICIs were characterized. Nine (43%) showed a durable clinical benefit (DCB), while the remaining 12 (57%) patients showed non-durable benefit (NDB). The M1 and peripheral T cell signatures showed the best performance for discriminating DCB from NDB (sensitivity, specificity, accuracy = 0.89, 1.0, 0.95, respectively). Progression-free survival (PFS) was significantly longer in patients with high M1 signature or high peripheral T cell signature scores. CD137 and PSMB9 mRNA expression was higher in the DCB group than in the NDB group. Patients with high PSMB9 expression showed longer PFS. M1 signature, peripheral T cell signature and high mRNA expression level of CD137 and PSMB9 showed better predictive performance than known biomarkers, such as PD-L1 immunohistochemistry, tumor mutation burden, or tumor-infiltrating lymphocytes.
Identification of emulsifier potato peptides by bioinformatics: application to omega-3 delivery emulsions and release from potato industry side streams
Authors: García-Moreno Pedro J. , Gregersen Simon , Nedamani Elham R. , Olsen Tobias H. , Marcatili Paolo , Overgaard Michael T. , Andersen Mogens L. , Hansen Egon B. , Jacobsen Charlotte
Published: January 2020

In this work, we developed a novel approach combining bioinformatics, testing of functionality and bottom-up proteomics to obtain peptide emulsifiers from potato side-streams. This is a significant advancement in the process to obtain emulsifier peptides and it is applicable to any type of protein. Our results indicated that structure at the interface is the major determining factor of the emulsifying activity of peptide emulsifiers. Fish oil-in-water emulsions with high physical stability were stabilized with peptides to be predicted to have facial amphiphilicity: (i) peptides with predominantly α-helix conformation at the interface and having 18–29 amino acids, and (ii) peptides with predominantly β-strand conformation at the interface and having 13–15 amino acids. In addition, high physically stable emulsions were obtained with peptides that were predicted to have axial hydrophobic/hydrophilic regions. Peptides containing the sequence FCLKVGV showed high in vitro antioxidant activity and led to emulsions with high oxidative stability. Peptide-level proteomics data and sequence analysis revealed the feasibility to obtain the potent emulsifier peptides found in this study (e.g. γ-1) by trypsin-based hydrolysis of different side streams in the potato industry.
Information Propagation Formalized Representation of Micro-blog Network Based on Petri Nets
Authors: Liang Xun , Zhang Shusen , Liu Yu , Ma Yuefeng
Published: January 2020

The description of user behavior in social networks is an important issue for studying social networks. Given that Petri nets can describe the resource flow problem, this study utilizes the features of Petri nets to portray the user behavior states during the message propagation of a micro-blog network and presents an information propagation formalized representation method of a micro-blog network. On this basis, this study analyzed the proposed formalized representation method in detail. We provide examples of applying formalized representation (e.g., micro-blog network addiction of users, user behavior influence, and public opinion analysis). In addition, we introduce the algorithms of formalized representation. We conduct experiments using Sina micro-blog data. Results show that the information propagation formalized representation method of micro-blog network based on Petri nets can depict user behaviors of micro-blog network intuitively and accurately. This study reveals a new perspective for information transmission of a micro-blog network and provides some tools to support public opinion monitoring and micro-blog marketing applications.
Prolonged production of 14C during the ~660 BCE solar proton event from Japanese tree rings
Authors: Sakurai Hirohisa , Tokanai Fuyuki , Miyake Fusa , Horiuchi Kazuho , Masuda Kimiaki , Miyahara Hiroko , Ohyama Motonari , Sakamoto Minoru , Mitsutani Takumi , Moriya Toru
Published: January 2020

Annual rings record the intensity of cosmic rays (CRs) that had entered into the Earth’s atmosphere. Several rapid 14C increases in the past, such as the 775 CE and 994CE 14C spikes, have been reported to originate from extreme solar proton events (SPEs). Another rapid 14C increase, also known as the ca. 660 BCE event in German oak tree rings as well as increases of 10Be and 36Cl in ice cores, was presumed similar to the 775 CE event; however, as the 14C increase of approximately 10‰ in 660 BCE had taken a rather longer rise time of 3–4 years as compared to that of the 775 CE event, the occurrence could not be simply associated to an extreme SPE. In this study, to elucidate the rapid increase in 14C concentrations in tree rings around 660 BCE, we have precisely measured the 14C concentrations of earlywoods and latewoods inside the annual rings of Japanese cedar for the period 669–633 BCE. Based on the feature of 14C production rate calculated from the fine measured profile of the 14C concentrations, we found that the 14C rapid increase occurred within 665–663.5 BCE, and that duration of 14C production describing the event is distributed from one month to 41 months. The possibility of occurrence of consecutive SPEs over up to three years is offered.
In vitro testing of a funnel-shaped tip catheter model to decrease clot migration during mechanical thrombectomy
Authors: Tanyildizi Yasemin , Payne Emily , Gerber Tiemo , Seidman Larissa , Heimann Axel , Kempski Oliver , Leithner Doris , Garcia-Bardon Andreas , Kloeckner Roman , Hahn Felix , Keric Naureen , Masomi-Bornwasser Julia , Brockmann Marc A. , Kirschner Stefanie
Published: January 2020

One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig’s blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.
Comparative efficacy and safety of warfarin care bundles and novel oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis
Authors: Ng Siok Shen , Lai Nai Ming , Nathisuwan Surakit , Jahan Nowrozy Kamar , Dilokthornsakul Piyameth , Kongpakwattana Khachen , Hollingworth William , Chaiyakunapruk Nathorn
Published: January 2020

Warfarin care bundles (e.g. genotype-guided warfarin dosing, patient’s self-testing [PST] or patient’s self-management [PSM] and left atrial appendage closure) are based on the concept of combining several interventions to improve anticoagulation care. NOACs are also introduced for stroke prevention in atrial fibrillation (SPAF). However, these interventions have not been compared in head-to-head trials yet. We did a network meta-analysis based on a systematic review of randomized controlled trials comparing anticoagulant interventions for SPAF. Studies comparing these interventions in adults, whether administered alone or as care bundles were included in the analyses. The primary efficacy outcome was stroke and the primary safety outcome was major bleeding. Thirty-seven studies, involving 100,142 patients were assessed. Compared to usual care, PSM significantly reduced the risk of stroke (risk ratio [RR] 0.24, 95% CI 0.08–0.68). For major bleeding, edoxaban 60 mg (0.80, 0.71–0.90), edoxaban 30 mg (0.48, 0.42–0.56), and dabigatran 110 mg (0.81, 0.71–0.94) significantly reduced the risk of major bleeding compared with usual warfarin care. Cluster rank plot incorporating stroke and major bleeding outcomes indicates that some warfarin care bundles perform as well as NOACs. Both interventions are therefore viable options to be considered for SPAF. Additional studies including head-to-head trials and cost-effectiveness evaluation are still warranted.
A Machine Learning Approach to Growth Direction Finding for Automated Planting of Bulbous Plants
Authors: Booth Brian G. , Sijbers Jan , De Beenhouwer Jan
Published: January 2020

In agricultural robotics, a unique challenge exists in the automated planting of bulbous plants: the estimation of the bulb’s growth direction. To date, no existing work addresses this challenge. Therefore, we propose the first robotic vision framework for the estimation of a plant bulb’s growth direction. The framework takes as input three x-ray images of the bulb and extracts shape, edge, and texture features from each image. These features are then fed into a machine learning regression algorithm in order to predict the 2D projection of the bulb’s growth direction. Using the x-ray system’s geometry, these 2D estimates are then mapped to the 3D world coordinate space, where a filtering on the estimate’s variance is used to determine whether the estimate is reliable. We applied our algorithm on 27,200 x-ray simulations from T. Apeldoorn bulbs on a standard desktop workstation. Results indicate that our machine learning framework is fast enough to meet industry standards (<0.1 seconds per bulb) while providing acceptable accuracy (e.g. error < 30° in 98.40% of cases using an artificial 3-layer neural network). The high success rates of the proposed framework indicate that it is worthwhile to proceed with the development and testing of a physical prototype of a robotic bulb planting system.
Clinical heterogeneity under induction with different dosages of cytarabine in core binding factor acute myeloid leukaemia
Authors: Wang Biao , Zhang Jihong , Hua Xiaoying , Li Haiqian , Wang Zhilin , Yang Bin
Published: January 2020

Repeated cycles of post-remission high-dose cytarabine (Ara-C) have been suggested to improve survival in core binding factor (CBF) acute myeloid leukaemia (AML). High-dose Ara-C used for induction regimens has also been reported to be associated with increased treatment-related mortality (TRM). Few data are available about intermediate-dose Ara-C serving as induction therapy. The aim of our study was to compare the tolerance and outcomes of standard- and intermediate-dose levels of Ara-C as induction in CBF AML and to analyse the clinical heterogeneity of the two AML entities under these induction settings. We retrospectively investigated the outcomes in adults with CBF AML induced with regimens based on standard-dose Ara-C at 100 to 200 mg/m2 or intermediate-dose Ara-C at 1,000 mg/m2. In total, 152 patients with t(8; 21) and 54 patients with inv(16) AML were administered an induction regimen containing anthracyclines plus either standard- or intermediate-dose Ara-C. After a single course of induction, the complete remission (CR) rate in the inv(16) cohort was 52/52 (100%), higher than the 127/147 (86.4%) in the t(8; 21) cohort (P = 0.005). Intermediate-dose Ara-C (HR = 9.931 [2.135–46.188], P = 0.003) and negative KITmut (HR = 0.304 [0.106–0.874], P = 0.027) independently produced an increased CR rate in the t(8; 21) cohort. Positive CD19 expression (HR = 0.133 [0.045–0.387], P = 0.000) and sex (male) (HR = 0.238 [0.085–0.667], P = 0.006) were associated with superior leukaemia-free survival (LFS) in the t(8; 21) cohort independently of KITmut status or the induction regimen. We conclude that intermediate-dose Ara-C is superior to standard-dose Ara-C for induction of remission in t(8; 21) AML, and CD19 status and sex independently confer prognostic significance for LFS. The KITmut status alone does not have an independent effect on survival in t(8; 21) AML. More intensive induction therapy is unnecessary in inv(16) AML.
Distribution Optimization: An evolutionary algorithm to separate Gaussian mixtures
Authors: Lerch Florian , Ultsch Alfred , Lötsch Jörn
Published: January 2020

Finding subgroups in biomedical data is a key task in biomedical research and precision medicine. Already one-dimensional data, such as many different readouts from cell experiments, preclinical or human laboratory experiments or clinical signs, often reveal a more complex distribution than a single mode. Gaussian mixtures play an important role in the multimodal distribution of one-dimensional data. However, although fitting of Gaussian mixture models (GMM) is often aimed at obtaining the separate modes composing the mixture, current technical implementations, often using the Expectation Maximization (EM) algorithm, are not optimized for this task. This occasionally results in poorly separated modes that are unsuitable for determining a distinguishable group structure in the data. Here, we introduce “Distribution Optimization” an evolutionary algorithm to GMM fitting that uses an adjustable error function that is based on chi-square statistics and the probability density. The algorithm can be directly targeted at the separation of the modes of the mixture by employing additional criterion for the degree by which single modes overlap. The obtained GMM fits were comparable with those obtained with classical EM based fits, except for data sets where the EM algorithm produced unsatisfactory results with overlapping Gaussian modes. There, the proposed algorithm successfully separated the modes, providing a basis for meaningful group separation while fitting the data satisfactorily. Through its optimization toward mode separation, the evolutionary algorithm proofed particularly suitable basis for group separation in multimodally distributed data, outperforming alternative EM based methods.
A Protein Interaction Information-based Generative Model for Enhancing Gene Clustering
Authors: Dutta Pratik , Saha Sriparna , Pai Sanket , Kumar Aviral
Published: January 2020

In the field of computational bioinformatics, identifying a set of genes which are responsible for a particular cellular mechanism, is very much essential for tasks such as medical diagnosis or disease gene identification. Accurately grouping (clustering) the genes is one of the important tasks in understanding the functionalities of the disease genes. In this regard, ensemble clustering becomes a promising approach to combine different clustering solutions to generate almost accurate gene partitioning. Recently, researchers have used generative model as a smart ensemble method to produce the right consensus solution. In the current paper, we develop a protein-protein interaction-based generative model that can efficiently perform a gene clustering. Utilizing protein interaction information as the generative model’s latent variable enables enhance the generative model’s efficiency in inferring final probabilistic labels. The proposed generative model utilizes different weak supervision sources rather utilizing any ground truth information. For weak supervision sources, we use a multi-objective optimization based clustering technique together with the world’s largest gene ontology based knowledge-base named Gene Ontology Consortium(GOC). These weakly supervised labels are supplied to a generative model that eventually assigns all genes to probabilistic labels. The comparative study with respect to silhouette score, Biological Homogeneity Index (BHI) and Biological Stability Index (BSI) proves that the proposed generative model outperforms than other state-of-the-art techniques.
Natural drivers of multidecadal Arctic sea ice variability over the last millennium
Authors: Halloran Paul R. , Hall Ian R. , Menary Matthew , Reynolds David J. , Scourse James D. , Screen James A. , Bozzo Alessio , Dunstone Nick , Phipps Steven , Schurer Andrew P. , Sueyoshi Tetsuo , Zhou Tianjun , Garry Freya
Published: January 2020

The climate varies due to human activity, natural climate cycles, and natural events external to the climate system. Understanding the different roles played by these drivers of variability is fundamental to predicting near-term climate change and changing extremes, and to attributing observed change to anthropogenic or natural factors. Natural drivers such as large explosive volcanic eruptions or multidecadal cycles in ocean circulation occur infrequently and are therefore poorly represented within the observational record. Here we turn to the first high-latitude annually-resolved and absolutely dated marine record spanning the last millennium, and the Paleoclimate Modelling Intercomparison Project (PMIP) Phase 3 Last Millennium climate model ensemble spanning the same time period, to examine the influence of natural climate drivers on Arctic sea ice. We show that bivalve oxygen isotope data are recording multidecadal Arctic sea ice variability and through the climate model ensemble demonstrate that external natural drivers explain up to third of this variability. Natural external forcing causes changes in sea-ice mediated export of freshwater into areas of active deep convection, affecting the strength of the Atlantic Meridional Overturning Circulation (AMOC) and thereby northward heat transport to the Arctic. This in turn leads to sustained anomalies in sea ice extent. The models capture these positive feedbacks, giving us improved confidence in their ability to simulate future sea ice in in a rapidly evolving Arctic.
Plasmonic ternary hybrid photocatalyst based on polymeric g-C3N4 towards visible light hydrogen generation
Authors: Che Yuping , Liu Qingqing , Lu Bingxin , Zhai Jin , Wang Kefeng , Liu Zhaoyue
Published: January 2020

Surface plasmon resonance (SPR) effect of noble metal nanoparticles (NPs) for photocatalysis has a significant enhancement. In this system, a plasmonic ternary hybrid photocatalyst of Ag/AgBr/g-C3N4was synthetized and used in water splitting to generation H2under visible light irradiation. 18%Ag/AgBr/g-C3N4showed the highest photoactivity, with the efficiency of hydrogen generation as high as 27-fold to that of pristine g-C3N4. Compared to simple mixture of Ag/AgBr and g-C3N4, hetero-composite Ag/AgBr/g-C3N4showed a higher photoactivity, even though they contained same content of Ag/AgBr. We find that significant factors for enhancing properties were the synergistic effect between Ag/AgBr and g-C3N4, and the light absorption enhancing by SPR effect of Ag NPs. Ag/AgBr NPs firmly anchored on the surface of g-C3N4and their high dispersion were also responsible for the improved activity and long-term recycling ability. The structure of Ag/AgBr/g-C3N4hybrid materials and their enhancement to photocatalytic activity were discussed. Meanwhile, the possible reaction mechanism of this system was proposed.
Manatee: detection and quantification of small non-coding RNAs from next-generation sequencing data
Authors: Handzlik Joanna E. , Tastsoglou Spyros , Vlachos Ioannis S. , Hatzigeorgiou Artemis G.
Published: January 2020

Small non-coding RNAs (sncRNAs) play important roles in health and disease. Next Generation Sequencing (NGS) technologies are considered as the most powerful and versatile methodologies to explore small RNA (sRNA) transcriptomes in diverse experimental and clinical studies. Small RNA-Seq (sRNA-Seq) data analysis proved to be challenging due to non-unique genomic origin, short length, and abundant post-transcriptional modifications of sRNA species. Here, we present Manatee, an algorithm for the quantification of sRNA classes and the detection of novel expressed non-coding loci. Manatee combines prior annotation of sRNAs with reliable alignment density information and extensive rescue of usually neglected multimapped reads to provide accurate transcriptome-wide sRNA expression quantification. Comparison of Manatee against state-of-the-art implementations using real and simulated data demonstrates its high accuracy across diverse sRNA classes. Manatee also goes beyond common pipelines by identifying and quantifying expression from unannotated loci and microRNA isoforms (isomiRs). It is user-friendly, can be easily incorporated in pipelines, and provides a simplified output suitable for direct usage in downstream analyses and functional studies.
Rice pyramided line IRBB67 (Xa4/Xa7) homeostasis under combined stress of high temperature and bacterial blight
Authors: Dossa Gerbert Sylvestre , Quibod Ian , Atienza-Grande Genelou , Oliva Ricardo , Maiss Edgar , Vera Cruz Casiana , Wydra Kerstin
Published: January 2020

Rice bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) implies substantial yield loss to rice. In times of climate change, increasing temperatures are observed and further acceleration is expected worldwide. Increasing temperature often turns into inhibition of host plant defense to pathogens. Recently, a reduced resistance in rice IRBB4 carrying Xa4, but an increase in resistance in IRBB7 carrying Xa7 resistance by increasing temperature has been reported. Influence of high temperature on both R genes (Xa4+Xa7) combined in IRBB67 was analyzed under growth chamber conditions and transcriptomic analysis performed. The pyramided line IRBB67 showed no differences in lesion length between both temperature regimes, demonstrating that non-effectiveness of Xa4 at high temperature did not affect IRBB67 resistance. Moreover, Xa4 complements Xa7 resistance with no Xoo spread in planta beyond the symptomatic area under both temperature regimes in IRBB67. Time course transcriptomic analysis revealed that temperature enhanced IRBB67 resistance to combined heat and Xoo. Our findings highlight altered cellular compartments and point at a role of the cell wall involved in Xoo resistance and heat stress tolerance in both susceptible (IR24) and the resistant (IRBB67) NILs. Interestingly, up-regulation of trehalose-6-phosphatase gene and low affinity cation transporter in IRBB67 suggest that IRBB67 maintained a certain homeostasis under high temperature which may have enhanced its resistance. The interplay of both heat stress and Xoo responses as determined by up-regulated and down-regulated genes demonstrates how resistant plants cope with combined biotic and abiotic stresses.
Extracellular NAD+ enhances PARP-dependent DNA repair capacity independently of CD73 activity
Authors: Wilk Anna , Hayat Faisal , Cunningham Richard , Li Jianfeng , Garavaglia Silvia , Zamani Leila , Ferraris Davide M. , Sykora Peter , Andrews Joel , Clark Jennifer , Davis Amanda , Chaloin Laurent , Rizzi Menico , Migaud Marie , Sobol Robert W.
Published: January 2020

Changes in nicotinamide adenine dinucleotide (NAD+) levels that compromise mitochondrial function trigger release of DNA damaging reactive oxygen species. NAD+ levels also affect DNA repair capacity as NAD+ is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (deacetylation). The ecto-5′-nucleotidase CD73, an ectoenzyme highly expressed in cancer, is suggested to regulate intracellular NAD+ levels by processing NAD+ and its bio-precursor, nicotinamide mononucleotide (NMN), from tumor microenvironments, thereby enhancing tumor DNA repair capacity and chemotherapy resistance. We therefore investigated whether expression of CD73 impacts intracellular NAD+ content and NAD+-dependent DNA repair capacity. Reduced intracellular NAD+ levels suppressed recruitment of the DNA repair protein XRCC1 to sites of genomic DNA damage and impacted the amount of accumulated DNA damage. Further, decreased NAD+ reduced the capacity to repair DNA damage induced by DNA alkylating agents. Overall, reversal of these outcomes through NAD+ or NMN supplementation was independent of CD73. In opposition to its proposed role in extracellular NAD+ bioprocessing, we found that recombinant human CD73 only poorly processes NMN but not NAD+. A positive correlation between CD73 expression and intracellular NAD+ content could not be made as CD73 knockout human cells were efficient in generating intracellular NAD+ when supplemented with NAD+ or NMN.
Analysis of O-glycoforms of the IgA1 hinge region by sequential deglycosylation
Authors: Ohyama Yukako , Yamaguchi Hisateru , Nakajima Kazuki , Mizuno Tomohiro , Fukamachi Yukihiro , Yokoi Yasuto , Tsuboi Naotake , Inaguma Daijo , Hasegawa Midori , Renfrow Matthew B. , Novak Jan , Yuzawa Yukio , Takahashi Kazuo
Published: January 2020

A common renal disease, immunoglobulin A (IgA) nephropathy (IgAN), is associated with glomerular deposition of IgA1-containing immune complexes. IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine with β1,3-linked galactose and variable sialylation. IgA1 glycoforms with some galactose-deficient (Gd) HR O-glycans play a key role in IgAN pathogenesis. The clustered and variable O-glycans make the IgA1 glycomic analysis challenging and better approaches are needed. Here, we report a comprehensive analytical workflow for IgA1 HR O-glycoform analysis. We combined an automated quantitative analysis of the HR O-glycopeptide profiles with sequential deglycosylation to remove all but Gd O-glycans from the HR. The workflow was tested using serum IgA1 from healthy subjects. Twelve variants of glycopeptides corresponding to the HR with three to six O-glycans were detected; nine glycopeptides carried up to three Gd O-glycans. Sites with Gd O-glycans were unambiguously identified by electron-transfer/higher-energy collision dissociation tandem mass spectrometry. Extracted ion chromatograms of isomeric glycoforms enabled quantitative assignment of Gd sites. The most frequent Gd site was T236, followed by S230, T233, T228, and S232. The new workflow for quantitative profiling of IgA1 HR O-glycoforms with site-specific resolution will enable identification of pathogenic IgA1 HR O-glycoforms in IgAN.
Effects of the Van der Waals Force on the Vibration of Typical Multi-layered Two-dimensional Nanostructures
Authors: Zhang Yiqing , Wang Lifeng
Published: January 2020

Recently, two-dimensional nanostructures have caught much attention because of their magnificent physical characteristics. The vibrational behavior of typical multi-layered two-dimensional nanostructures (TMLTNs) is extraordinary significant to TMLTN-based nanoresonantors. In this investigation, the vibrational behavior of TMLTNs, taking black phosphorus (BP), graphene and BN as examples, is studied adopting molecular dynamics (MD) simulations and the sandwich plate model (SPM). The MD results show that the fundamental resonant frequency of multi-layered BP (MLBP) and multi-layered BN (MLBN) increase obviously with the number of layers. However, the fundamental resonant frequency of a multi-layered graphene sheet (MLGS) rise slightly when the number of layers increases. This phenomenon is caused by the shear modulus in the xz-plane and yz-plane resulted by the vdW force. Hence, an SPM considering the shear modulus in the xz-plane and yz-plane caused by the vdW force is used to investigate the vibration of the TMLTN. Compared with the MD results, it is shown that the SPM can better predict the vibration of the TMLTN.
Exploring ion-ion preferences through structure-property correlations: amino acid-derived, bis(guanidinium) disiloxane salts
Authors: Tabisz Łukasz , Rozwadowski Zbigniew , Katrusiak Andrzej , Łęska Bogusława
Published: January 2020

In a more synthetical approach to the study of ion-specific phenomena, four dipodal bis(guanidinium) siloxanes have been synthesized starting from glycine, β-alanine, γ-aminobutanoic acid, L-proline and 1,3-bis(3-aminopropyl)tetramethyldisiloxane. Together with their non-amide progenitor they were comparatively studied in regards to their interactions with nine different anions: sulphate, chromate, molybdate, benzoate, chloride, azide, nitrite, nitrate and thiocyanate. Their aqueous solubilities, form, 1H NMR and FT-IR spectra were examined while searching for anion-specific interactions falling in- or outside of the Hofmeister series. We show that although the “chao-” and “kosmotropic” ions affect the properties of solutions in a predictable way, more selective cation-anion pairing is responsible for phase separation and crystallinity. As a prominent example, crystal structure of one of the benzoate salts was successfully obtained and reveals a synergy of hydrophobic packing, ionic and hydrogen bonding. Immobilized but still flexible siloxane bridges give rise to crystals described by P 42/n space group and neatly segregated into hydro- and lipophilic sections.
Autogenous Healing in Cementitious Materials with Superabsorbent Polymers Quantified by Means of NMR
Authors: Snoeck D. , Pel L. , De Belie N.
Published: January 2020

A recent advance in construction technology is the use of self-healing cementitious materials containing synthetic microfibers and superabsorbent polymers. By stimulating autogenous healing by means of superabsorbent polymers, cracks are closed and this will cause an increase in durability and service life. However, this improved healing capacity has not been quantified yet in terms of increased further hydration and volume of healing products. This is needed to model the material and to stimulate the practical application in constructions. This paper provides quantitative data, obtained by an NMR study. Addition of 1 m% of selected superabsorbent polymer versus cement to a cementitious material, stimulated further hydration with nearly 40% in comparison with a traditional cementitious material, if 1 h water contact per day was allowed. At 90% relative humidity, no healing was observed in reference samples. While the further hydration around a crack in specimens with superabsorbent polymers was still 68% of that of a reference system with cyclic water contact, due to the uptake of moisture by the superabsorbent polymers. As such, NMR results quantify the positive influence of superabsorbent polymers in terms of stimulated autogenous healing and substantiate their benefits for application in the construction area.
Molecular phylogeny of one extinct and two critically endangered Central Asian sturgeon species (genus Pseudoscaphirhynchus) based on their mitochondrial genomes
Authors: Nedoluzhko Artem V. , Sharko Fedor S. , Tsygankova Svetlana V. , Boulygina Eugenia S. , Barmintseva Anna E. , Krasivskaya Anna A. , Ibragimova Amina S. , Gruzdeva Natalia M. , Rastorguev Sergey M. , Mugue Nikolai S.
Published: January 2020

The enigmatic and poorly studied sturgeon genus Pseudoscaphirhynchus (Scaphirhynchinae: Acipenseridae) comprises three species: the Amu Darya shovelnose sturgeon (Pseudoscaphirhynchus kaufmanni (Bogdanow)), dwarf Amu Darya shovelnose sturgeon P. hermanni (Kessler), and Syr Darya shovelnose sturgeon (P. fedtschenkoi (Bogdanow). Two species – P. hermanni and P. kaufmanni – are critically endangered due to the Aral Sea area ecological disaster, caused by massive water use for irrigation to support cotton agriculture, subsequent pesticide pollution and habitat degradation. For another species – P. fedtschenkoi – no sightings have been reported since 1960-s and it is believed to be extinct, both in nature and in captivity. In this study, complete mitochondrial (mt) genomes of these three species of Pseudoscaphirhynchus were characterized using Illumina and Sanger sequencing platforms. Phylogenetic analyses showed the significant divergence between Amu Darya and Syr Darya freshwater sturgeons and supported the monophyletic origin of the Pseudoscaphirhynchus species. We confirmed that two sympatric Amu Darya species P. kaufmanni and P. hermanni form a single genetic cluster, which may require further morphological and genetic study to assess possible hybridization, intraspecific variation and taxonomic status and to develop conservation measures to protect these unique fishes.
Ventral striatum supports Methylphenidate therapeutic effects on impulsive choices expressed in temporal discounting task
Authors: Martinez Eva , Pasquereau Benjamin , Drui Guillaume , Saga Yosuke , Météreau Élise , Tremblay Léon
Published: January 2020

Methylphenidate (MPH) is a dopamine transporter (DAT) inhibitor used to treat attention-deficit/hyperactivity-disorder (ADHD). ADHD patients make impulsive choices in delay discounting tasks (DDT) and MPH reduces such impulsivity, but its therapeutic site of action remains unknown. Based on the high density of DAT in the striatum, we hypothesized that the striatum, especially the ventral striatum (VS) and caudate nucleus which both encode temporal discounting, can be preferential MPH action sites. To determine whether one of these striatal territories is predominantly involved in the effect of MPH, we trained monkeys to make choices during DDT. First, consistent with clinical observations, we found an overall reduction of impulsive choices with a low dose of MPH administered via intramuscular injections, whereas we reported sedative-like effects with a higher dose. Then, using PET-imaging, we found that the therapeutic reduction of impulsive choices was associated with selective DAT occupancy of MPH in the VS. Finally, we confirmed the selective involvement of the VS in the effect of MPH by testing the animals’ impulsivity with microinjections of the drug in distinct striatal territories. Together, these results show that the therapeutic effect of MPH on impulsive decisions is mainly restricted to its action in the VS.
Reliability of Frontal Eye Fields Activation and Very Low-Frequency Oscillations Observed during Vergence Eye Movements: an fNIRS Study
Authors: Yaramothu Chang , Li Xiaobo , Morales Cristian , Alvarez Tara L.
Published: January 2020

Functional near-infrared spectroscopy (fNIRS), an imaging tool that utilizes infrared light to measure changes within the concentration of oxygenated (HbO) and deoxygenated (HbR) hemoglobin, holds promise to study functional activity from motor, visual, and memory cortical regions using stimulus-induced tasks. This study investigated the reliability for fNIRS to examine cortical activations within the frontal eye fields (FEF) while initiating vergence eye movements, the inward and outward rotation of the eyes. FNIRS data were collected from twenty participants with normal binocular vision while performing vergence eye movements compared to sustained gaze fixation within a block design during two different sessions. Reliability of the experimental protocol was assessed using the intraclass correlation coefficient (ICC). The ICC values ranged from 0.6 to 0.7 for measuring the HbO activation within the vicinity of the FEF. A frequency power spectrum analysis revealed two predominant frequencies within the functional activation signals from the FEF. One high-intensity signal was present at 0.029 Hz, centering around the block design frequency. The peak-intensity signal was observed between 0.012 and 0.018 Hz where this very low-frequency oscillation (VLFO) was hypothesized to be generated by the macrovasculature present near the FEF and should be avoided as a block design frequency in future fNIRS studies to avoid false positive results.