bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Aspects of International Treaties Banning the Proliferation of Nuclear Weapons and Their Significance for the Kyrgyz Republic
Authors: Toktobaev B. , Karabalaeva S.
Published: January 2021

The article considers international legal acts regulating the scope of international security law in the field of nuclear weapons, their varieties, analysis of articles of the Treaty on the Non-Proliferation of Nuclear Weapons, as well as their significance for the Kyrgyz Republic.
Analysis of the Effectiveness of the Mechanism for the Correction of Judicial Errors by the Courts of Appeal and Cassation, Within the Framework of the Judicial Reform
Authors: Platonova K. , Koval K. , Shumova
Published: January 2021

Within the framework of this article, the features of the review of cases are disclosed, in order to correct the admitted judicial errors, in the order of instance by the courts of appeal and cassation. The importance and effectiveness of the transformation of courts of appeal and cassation under the influence of the ongoing judicial reform is analyzed.
Analysis of the Formation of Conflictological Competence of a Modern Teacher
Authors: Smirnova E.
Published: January 2021

This article examines the problem of the formation of conflictological competence, which is fundamental in the teacher’s professiogram. Namely, the reasons for the high conflict potential of the educational environment, the possibility of its optimization. The article describes the analysis of the teacher’s conflictological competence from the standpoint of its essence and structure, as well as the possibility of its development.
Interactional Competence or Communicative Competence: Overview of Related Theories
Authors: Kertaeva Z.
Published: January 2021

The article analyses the relationship of communicative and interactional competences by providing chronological evolution of the terms and discussing contrasting and similar approaches the language scholars presented earlier. Besides, relevant examples for issues of testing and assessing these two competences are illustrated to show the gaps between communicative teaching and testing.
Using Web Technologies in Effective Teaching of Mathematics at Universities
Authors: Yakubova U. , Parpieva N. , Mirhojaeva N.
Published: January 2021

The article describes the role of web technologies in effective teaching of mathematics at universities. The advantages of the use of WebQuests are defined. This study aims to examine the effect of WebQuests used in instruction on students’ academic achievements and the student and teacher opinions on WebQuests.
Human Way of Life as a Form of Organization of Being
Authors: Petrov I.
Published: January 2021

Limiting a person’s lifestyle to objective social conditions is usually due to the fact that they determine the essence and nature of people's life activities. However, not only social, but also natural factors determine people’s life activity. The article shows that the way of life of people can be studied only in unity with the conditions of life. Its essence should be revealed taking into account the influence of natural and social conditions on it. This means that the concepts of “living conditions” and “lifestyle” are inseparable, but it does not mean that one of them becomes an integral part of the other. In fact, living conditions, or rather the natural and social spheres, only describe the possible range of people’s activities. It is emphasized that not only living conditions shape the way of life of a person, but he himself changes the surrounding conditions, both social and natural, during his life.
Values as Defining Elements of Culture
Authors: Petrova S.
Published: January 2021

The article considers values as one of the defining elements of culture. It is noted that culture in the value aspect is a kind of social mechanism that allows a person to navigate in the surrounding space. Value ensures the integration of society, helps a person make the right (socially approved) decision. In the course of the historical development of a society, several parallel processes take place in its culture: development, modernization and preservation, stability, and continuity. On the one hand, culture absorbs or creates new values, and on the other hand, it preserves its identity. The integrity of culture is guaranteed by social selection. Any culture retains at its core only what corresponds to its logic.
Sub-Regional Differences of the Human Amniotic Membrane and Their Potential Impact on Tissue Regeneration Application
Authors: Weidinger Adelheid , Poženel Laura , Wolbank Susanne , Banerjee Asmita
Published: January 2021

For more than 100 years, the human amniotic membrane (hAM) has been used in multiple tissue regeneration applications. The hAM consists of cells with stem cell characteristics and a rich layer of extracellular matrix. Undoubtedly, the hAM with viable cells has remarkable properties such as the differentiation potential into all three germ layers, immuno-modulatory, and anti-fibrotic properties. At first sight, the hAM seems to be one structural entity. However, by integrating its anatomical location, the hAM can be divided into placental, reflected, and umbilical amniotic membrane. Recent studies show that cells of these amniotic sub-regions differ considerably in their properties such as morphology, structure, and content/release of certain bioactive factors. The aim of this review is to summarize these findings and discuss the relevance of these different properties for tissue regeneration. In summary, reflected amnion seems to be more immuno-modulatory and could have a higher reprogramming efficiency, whereas placental amnion seems to be pro-inflammatory, pro-angiogenic, with higher proliferation and differentiation capacity (e.g., chondrogenic and osteogenic), and could be more suitable for certain graft constructions. Therefore, we suggest that the respective hAM sub-region should be selected in consideration of its desired outcome. This will help to optimize and fine-tune the clinical application of the hAM.
Metabolic Glycoengineering Enables the Ultrastructural Visualization of Sialic Acids in the Glycocalyx of the Alveolar Epithelial Cell Line hAELVi
Authors: Brandt Raphael , Timm Sara , Gorenflos López Jacob L. , Kwame Abledu Jubilant , Kuebler Wolfgang M. , Hackenberger Christian P. R. , Ochs Matthias , Lopez-Rodriguez Elena
Published: January 2021

The glycocalyx—a plethora of sugars forming a dense layer that covers the cell membrane—is commonly found on the epithelial surface of lumen forming tissue. New glycocalyx specific properties have been defined for various organs in the last decade. However, in the lung alveolar epithelium, its structure and functions remain almost completely unexplored. This is partly due to the lack of physiologically relevant, cost effective in vitro models. As the glycocalyx is an essential but neglected part of the alveolar epithelial barrier, understanding its properties holds the promise to enhance the pulmonary administration of drugs and delivery of nanoparticles. Here, using air-liquid-interface (ALI) cell culture, we focus on combining metabolic glycoengineering with glycan specific electron and confocal microscopy to visualize the glycocalyx of a recently immortalized human alveolar epithelial cell line (hAELVi). For this purpose, we applied different bioorthogonal labeling approaches to visualize sialic acid—an amino sugar that provides negative charge to the lung epithelial glycocalyx—using both fluorescence and gold-nanoparticle labeling. Further, we compared mild chemical fixing/freeze substitution and standard cytochemical electron microscopy embedding protocols for their capacity of contrasting the glycocalyx. In our study, we established hAELVi cells as a convenient model for investigating human alveolar epithelial glycocalyx. Transmission electron microscopy revealed hAELVi cells to develop ultrastructural features reminiscent of alveolar epithelial type II cells (ATII). Further, we visualized extracellular uni- and multilamellar membranous structures in direct proximity to the glycocalyx at ultrastructural level, indicating putative interactions. The lamellar membranes were able to form structures of higher organization, and we report sialic acid to be present within those. In conclusion, combining metabolite specific glycoengineering with ultrastructural localization presents an innovative method with high potential to depict the molecular distribution of individual components of the alveolar epithelial glycocalyx and its interaction partners.
High-Throughput Plant Phenotyping Platform (HT3P) as a Novel Tool for Estimating Agronomic Traits From the Lab to the Field
Authors: Li Daoliang , Quan Chaoqun , Song Zhaoyang , Li Xiang , Yu Guanghui , Li Cheng , Muhammad Akhter
Published: January 2021

Food scarcity, population growth, and global climate change have propelled crop yield growth driven by high-throughput phenotyping into the era of big data. However, access to large-scale phenotypic data has now become a critical barrier that phenomics urgently must overcome. Fortunately, the high-throughput plant phenotyping platform (HT3P), employing advanced sensors and data collection systems, can take full advantage of non-destructive and high-throughput methods to monitor, quantify, and evaluate specific phenotypes for large-scale agricultural experiments, and it can effectively perform phenotypic tasks that traditional phenotyping could not do. In this way, HT3Ps are novel and powerful tools, for which various commercial, customized, and even self-developed ones have been recently introduced in rising numbers. Here, we review these HT3Ps in nearly 7 years from greenhouses and growth chambers to the field, and from ground-based proximal phenotyping to aerial large-scale remote sensing. Platform configurations, novelties, operating modes, current developments, as well the strengths and weaknesses of diverse types of HT3Ps are thoroughly and clearly described. Then, miscellaneous combinations of HT3Ps for comparative validation and comprehensive analysis are systematically present, for the first time. Finally, we consider current phenotypic challenges and provide fresh perspectives on future development trends of HT3Ps. This review aims to provide ideas, thoughts, and insights for the optimal selection, exploitation, and utilization of HT3Ps, and thereby pave the way to break through current phenotyping bottlenecks in botany.
Cell Proliferation and Collective Cell Migration During Zebrafish Lateral Line System Development Are Regulated by Ncam/Fgf-Receptor Interactions
Authors: Dries Ramona , Lange Annemarie , Heiny Sebastian , Berghaus Katja I. , Bastmeyer Martin , Bentrop Joachim
Published: January 2021

The posterior lateral line system (pLLS) of aquatic animals comprises small clustered mechanosensory organs along the side of the animal. They develop from proneuromasts, which are deposited from a migratory primordium on its way to the tip of the tail. We here show, that the Neural Cell Adhesion Molecule Ncam1b is an integral part of the pathways initiating and regulating the development of the pLLS in zebrafish. We find that morpholino-knockdowns ofncam1b(i) reduce cell proliferation within the primordium, (ii) reduce the expression of Fgf target geneerm, (iii) severely affect proneuromast formation, and (iv) affect primordium migration. Ncam1b directly interacts with Fgf receptor Fgfr1a, and a knockdown offgfr1acauses similar phenotypic changes as observed inncam1b-morphants. We conclude that Ncam1b is involved in activating proliferation by triggering the expression oferm. In addition, we demonstrate that Ncam1b is required for the expression of chemokine receptor Cxcr7b, which is crucial for directed primordial migration. Finally, we show that the knockdown ofncam1bdestabilizes proneuromasts, suggesting a further function of Ncam1b in strengthening the cohesion of proneuromast cells.
Microsecond MD Simulation and Multiple-Conformation Virtual Screening to Identify Potential Anti-COVID-19 Inhibitors Against SARS-CoV-2 Main Protease
Authors: Selvaraj Chandrabose , Panwar Umesh , Dinesh Dhurvas Chandrasekaran , Boura Evzen , Singh Poonam , Dubey Vikash Kumar , Singh Sanjeev Kumar
Published: January 2021

The recent pandemic outbreak of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raised global health and economic concerns. Phylogenetically, SARS-CoV-2 is closely related to SARS-CoV, and both encode the enzyme main protease (Mpro/3CLpro), which can be a potential target inhibiting viral replication. Through this work, we have compiled the structural aspects of Mpro conformational changes, with molecular modeling and 1-μs MD simulations. Long-scale MD simulation resolves the mechanism role of crucial amino acids involved in protein stability, followed by ensemble docking which provides potential compounds from the Traditional Chinese Medicine (TCM) database. These lead compounds directly interact with active site residues (His41, Gly143, and Cys145) of Mpro, which plays a crucial role in the enzymatic activity. Through the binding mode analysis in the S1, S1′, S2, and S4 binding subsites, screened compounds may be functional for the distortion of the oxyanion hole in the reaction mechanism, and it may lead to the inhibition of Mpro in SARS-CoV-2. The hit compounds are naturally occurring compounds; they provide a sustainable and readily available option for medical treatment in humans infected by SARS-CoV-2. Henceforth, extensive analysis through molecular modeling approaches explained that the proposed molecules might be promising SARS-CoV-2 inhibitors for the inhibition of COVID-19, subjected to experimental validation.
Identification of Chalcone Derivatives as Inhibitors of Leishmania infantum Arginase and Promising Antileishmanial Agents
Authors: Garcia Andreza R. , Oliveira Danielle M. P. , Jesus Jessica B. , Souza Alessandra M. T. , Sodero Ana Carolina R. , Vermelho Alane B. , Leal Ivana C. R. , Souza Rodrigo Octavio M. A. , Miranda Leandro S. M. , Pinheiro Anderson S. , Rodrigues Igor A.
Published: January 2021

Arginase catalyzes the hydrolysis of l-arginine into l-ornithine and urea, acting as a key enzyme in the biosynthesis of polyamines. Leishmania growth and survival is dependent on polyamine biosynthesis; therefore, inhibition of Leishmania arginase may be a promising therapeutic strategy. Here, we evaluated a series of thirty-six chalcone derivatives as potential inhibitors of Leishmania infantum arginase (LiARG). In addition, the activity of selected inhibitors against L. infantum parasites was assessed in vitro. Seven compounds exhibited LiARG inhibition above 50% at 100 μM. Among them, compounds LC41, LC39, and LC32 displayed the greatest inhibition values (72.3 ± 0.3%, 71.9 ± 11.6%, and 69.5 ± 7.9%, respectively). Molecular docking studies predicted hydrogen bonds and hydrophobic interactions between the most active chalcones (LC32, LC39, and LC41) and specific residues from LiARG's active site, such as His140, Asn153, His155, and Ala193. Compound LC32 showed the highest activity against L. infantum promastigotes (IC50 of 74.1 ± 10.0 μM), whereas compounds LC39 and LC41 displayed the best results against intracellular amastigotes (IC50 of 55.2 ± 3.8 and 70.4 ± 9.6 μM, respectively). Moreover, compound LC39 showed more selectivity against parasites than host cells (macrophages), with a selectivity index (SI) of 107.1, even greater than that of the reference drug Fungizone®. Computational pharmacokinetic and toxicological evaluations showed high oral bioavailability and low toxicity for the most active compounds. The results presented here support the use of substituted chalcone skeletons as promising LiARG inhibitors and antileishmanial drug candidates.
GPU-Accelerated Machine Learning Inference as a Service for Computing in Neutrino Experiments
Authors: Wang Michael , Yang Tingjun , Flechas Maria Acosta , Harris Philip , Hawks Benjamin , Holzman Burt , Knoepfel Kyle , Krupa Jeffrey , Pedro Kevin , Tran Nhan
Published: January 2021

Machine learning algorithms are becoming increasingly prevalent and performant in the reconstruction of events in accelerator-based neutrino experiments. These sophisticated algorithms can be computationally expensive. At the same time, the data volumes of such experiments are rapidly increasing. The demand to process billions of neutrino events with many machine learning algorithm inferences creates a computing challenge. We explore a computing model in which heterogeneous computing with GPU coprocessors is made available as a web service. The coprocessors can be efficiently and elastically deployed to provide the right amount of computing for a given processing task. With our approach, Services for Optimized Network Inference on Coprocessors (SONIC), we integrate GPU acceleration specifically for the ProtoDUNE-SP reconstruction chain without disrupting the native computing workflow. With our integrated framework, we accelerate the most time-consuming task, track and particle shower hit identification, by a factor of 17. This results in a factor of 2.7 reduction in the total processing time when compared with CPU-only production. For this particular task, only 1 GPU is required for every 68 CPU threads, providing a cost-effective solution.
Interdecadal Change in the Relationship Between the Bay of Bengal Summer Monsoon and South China Sea Summer Monsoon Onset
Authors: Zeng Zhenjie , Guo Yuanyuan , Wen Zhiping
Published: January 2021

The interdecadal change of the BOBSM–SCSSM relationship around the late 1970s is investigated in this paper. We found that the correlation between the BOBSM and SCSSM is 0.22 in 1958–1979, while it is 0.66 in 1980–2018. Further analyses showed that the strength of the South Asian High (SAH) at upper troposphere circulation experiences an interdecadal enhancement around the late 1970s; meanwhile its meridional shift exhibits a wider range in the second subperiod. Both the interdecadal change of the strength and meridional shift of the SAH contribute to a closer relationship of the BOBSM and SCSSM through modulating the divergent field at upper troposphere. As for the external forcing, the basin warming of the Indian Ocean after the late 1970s may serve as a relatively primary factor, which could induce a consistent background flow that may favor a closer BOBSM–SCSSM relationship in the second period. It is noted that the Indian Ocean warming is related to high pressure anomaly widely lying to the south of 20°N at upper troposphere, accompanied by the low pressure anomaly center to the north of 20°N. And this kind of upper-level circulation may result in strong westerly anomaly at the domain where the pressure gradient is large and then modulate the onset of the BOBSM and SCSSM in 1980–2018 through changing the upper-level divergent field. Besides, the low troposphere circulation associated with Indian Ocean warming is featured by the zonal-elongated high pressure anomaly spanning from the BOB and SCS to the northwest Pacific. The above coupling of the upper and lower troposphere, as a larger-scale consistent background flow controls the BOB and SCS, can modulate the interannual variation of the BOBSM and SCSSM synchronously and contributes to the closer relationship of the BOBSM and SCSSM in the second subperiod.
Teacher Practices, Peer Dynamics, and Academic Enablers: A Pilot Study Exploring Direct and Indirect Effects Among Children at Risk for ADHD and Their Classmates
Authors: Owens Julie Sarno , Qi Hongyuan , Himawan Lina K. , Lee Mary , Mikami Amori Yee
Published: January 2021

Establishing a positive peer climate in elementary school classrooms is an important goal for educators because peer dynamics are thought to affect academic learning. Thus, it is important to (a) understand the relationship between children's peer dynamics and academic functioning, and (b) identify teacher practices that influence both peer processes and academic outcomes. In this pilot study, we explored whether specific teacher strategies that promote positive behaviors in children and positive peer dynamics influence children's better academic enablers, as well as whether they do so indirectly via improving peer sociometric ratings. Such teacher strategies may be particularly relevant for supporting children who demonstrate impairment in both social and academic domains, such as children at risk for attention-deficit/hyperactivity disorder (ADHD). Thus, we also examined whether these relationships differ for children with elevated ADHD symptoms and peer problems (i.e., target students), relative to classmates (i.e., non-target students). Participants were 194 children in the classrooms of 12 teachers (grades K-4) who participated in an open-trial pilot study of the school-based version of the Making Socially Accepting Inclusive Classrooms (MOSAIC) program. In the fall and spring of a school year, we assessed children's sociometric ratings received from peers, and academic enabler skills as rated by teachers. Throughout one academic year, we obtained assessments of teachers' use of MOSAIC strategies (observed and self-reported). Results showed that, after accounting for fall academic enablers, the teacher strategy of CARE time (involving one-on-one interaction with the student to build the teacher-student relationship) was positively associated with spring academic enablers. However, findings did not support the hypothesized indirect effect of peer sociometric ratings on the relationship between teacher strategy use and academic enablers, or the moderated indirect effect by target student status. Implications for future research and classroom interventions are discussed.
A Call for Rethinking Schooling and Leadership in the Time of COVID-19
Authors: Rincones Rodolfo , Peña Isela , Canaba Karina Chantal
Published: January 2021

COVID-19 forced a sudden closure of schools, prompting a hasty and unplanned reaction of educators to deliver educational content. Inspired by Ivan Illich's book Deschooling Society, where he argues for the delivery of educational content by utilizing technology and forging intentional partnerships with parents and communities to assist in the delivery of educational content, we reflect on how these ideas impact school leadership and preparation of school leaders. This “forced” deschooling has offered educators an opportunity to rethink the true purpose of education, and redesign flexible, creative and innovative instructional strategies for delivering educational materials and knowledge, as well as rethinking the role of and preparation of educational leaders. While we do not offer quick solutions, our intent is to revisit Illich's Deschooling Society as a means to examine and question our school system introspectively and collectively.
Associations of Prenatal Exposure to Triclosan and Maternal Thyroid Hormone Levels: A Systematic Review and Meta-Analysis
Authors: Chen Danrong , Liu Jiani , Yan Wu , Fang Kacey , Xia Yankai , Lv Wei , Shi Zhonghua
Published: January 2021

Objective

To quantitatively evaluate associations between exposure to triclosan during pregnancy and maternal thyroid hormone levels.

Method

The databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched to identify relevant studies on the relationship between prenatal exposure to triclosan and maternal levels of serum thyroid hormone published before October 22, 2019. Stata 12.0 was used to examine the heterogeneity among the eligible studies.

Results

Seven studies involving a total of 4,136 participants were included. Overall, descriptive analysis provided no indication that exposure to TCS during pregnancy was related to either maternal FT4 levels (ES = 0.01, 95% CI: −0.03 to 0.05, P = 0.00) or TSH levels (ES = −0.03, 95% CI: −0.13 to 0.07, P = 0.412). Although the results were statistically insignificant, with the increase of urine TCS concentration, maternal FT4 levels exhibited a tendency to increase while TSH levels had a tendency to decrease during pregnancy.

Conclusion

The results indicated that exposure to triclosan during pregnancy has no significant influence on maternal levels of thyroid hormone. On account of the inconsistency of existing research designs and study locations, further studies and replication are necessary to confirm these findings.
Dynamic Characteristics of Accelerator-Driven Subcritical Reactor With Self-Adapting Multi-Mode Core Few-Group Constants
Authors: Deng Nianbiao , Xie Jinsen , Hou Cheng , Zeng Wenjie , Chen Zhenping , Yu Tao , Zhao Pengcheng , Liu Zijing , Xie Chao , Xie Qin
Published: January 2021

In this study, the dynamic characteristics of accelerator-driven subcritical reactor (ADSR) under beam transients with high heterogeneity of neutron flux in time-space are investigated. Multi-mode core few-group constants are generated by three kinds of neutron fluxes: steady state of ADSR, λ-eigenvalue fundamental wave, and α-eigenvalue fundamental wave. The proposed few-group constants overcome the limitation of single few-group constant generated by two-step method that cannot consider the variation in neutron flux density and neutron energy spectrum with time and space. Compared to the existing few-group constants generated by two-step method under different operating conditions, the self-adapting multi-mode core few-group constants exhibit higher accuracy in the case of following two modes: steady-state mode of ADSR in the starting process and λ-eigenvalue mode in the beam trip condition. Overall, this research provides useful insights on neutron kinetics and can boost the development of ADSRs.
High Application Rates of Biochar to Mitigate N2O Emissions From a N-Fertilized Tropical Soil Under Warming Conditions
Authors: Rittl Tatiana F. , Oliveira Dener M. S. , Canisares Luiza P. , Sagrilo Edvaldo , Butterbach-Bahl Klaus , Dannenmann Michael , Cerri Carlos E. P.
Published: January 2021

Biochar application has been suggested as a strategy to decrease nitrous oxide emissions from agricultural soils while increasing soil C stocks, especially in tropical regions. Climate change, specifically increasing temperatures, will affect soil environmental conditions and thereby directly influence soil N2O fluxes. Here, we show that Miscanthus giganteus biochar applied at high rates suppresses the typical warming-induced stimulation of N2O emissions. Specifically, in experiments with high biochar addition (25 Mg ha−1), N2O emissions under 40°C were equal to or even lower compared to those observed at 20°C. In this sense, the mitigation potential of biochar for N2O emissions might increase under the auspices of climate change.
Specialist Birds Replace Generalists in Grassland Remnants as Land Use Change Intensifies
Authors: Staude Ingmar R. , Overbeck Gerhard E. , Fontana Carla Suertegaray , Bencke Glayson A. , Silva Thaiane Weinert da , Mimet Anne , Pereira Henrique M.
Published: January 2021

The ideal free distribution theory predicts that mobile species distribute themselves among habitat patches so as to optimize their fitness. Changes in land use alter the quality of habitat patches and thereby affect the distribution of species. Following the loss of native habitat, habitat specialists are expected to move to patches where native habitat still remains in order to survive. Competition for resources in habitat remnants should consequently increase. As generalists are able to use other habitats, generalists are expected to gradually disappear in remnants in order to avoid increasing competition with specialists. Here, we test these predictions by studying the response of habitat specialist and generalist birds to land-use change in Brazil's southern grasslands. Using a space-for-time substitution approach, we surveyed bird communities in native grassland sites (~4 ha) in 31 regions (10 × 10 km) with differing levels of conversion to agriculture (1–94%). We found a higher abundance of specialists in native grassland patches with increasing agricultural cover in the region, while the total number of individuals in remnants remained constant. At the same time, the share of generalists in total abundance and total species richness decreased. To gain insights into whether these patterns could be driven by shifts in competition, we tested whether generalists that continued to co-occur with specialists in remnants, had less dietary overlap with specialists. As a consequence of community composition in remnants, a higher proportion of generalists were omnivorous and the average generalist species fed less on seeds, whereas the average specialist species fed more on seeds when agricultural cover was high in the region. Our results, therefore, support predictions of the ideal free distribution theory. Specialists that are assumed to have a low survivorship outside of their specialized habitat, distribute to remnants of this habitat when it is converted elsewhere, while generalists, being able to survive in other habitats, disappear gradually in remnants. Such a process could partly explain the segregation of habitat specialist and generalist birds observed in many agricultural landscapes. Finally, our results suggest that native habitat remnants can be important temporary refugia for specialists.
Reticulate Evolution, Ancient Chloroplast Haplotypes, and Rapid Radiation of the Australian Plant Genus Adenanthos (Proteaceae)
Authors: Nge Francis J. , Biffin Ed , Thiele Kevin R. , Waycott Michelle
Published: January 2021

Cytonuclear discordance, commonly detected in phylogenetic studies, is often attributed to hybridization and/or incomplete lineage sorting (ILS). New sequencing technologies and analytical approaches can provide new insights into the relative importance of these processes. Hybridization has previously been reported in the Australian endemic plant genusAdenanthos(Proteaceae). Like many Australian genera,Adenanthosis of relatively ancient origin, and provides an opportunity to examine long-term evolutionary consequences of gene flow between lineages. Using a hybrid capture approach, we assembled densely sampled low-copy nuclear and plastid DNA sequences forAdenanthos, inferred its evolutionary history, and used a Bayesian posterior predictive approach and coalescent simulations to assess relative contributions of hybridization and ILS to cytonuclear discordance. Our analyses indicate that strong incongruence detected between our plastid and nuclear phylogenies is not only the result of ILS, but also results from extensive ancient introgression as well as recent chloroplast capture and introgression between extantAdenanthosspecies. The deep reticulation was also detected from long-persisting chloroplast haplotypes shared between evolutionarily distant species. These haplotypes may have persisted for over 12 Ma in localized populations across southwest Western Australia, indicating that the region is not only an important area for old endemic lineages and accumulation of species, but is also characterized by persistence of high genetic diversity. Deep introgression inAdenanthoscoincided with the rapid radiation of the genus during the Miocene, a time when many Australian temperate plant groups radiated in response to large-scale climatic change. This study suggests that ancient introgression may play an important role in the evolution of the Australian flora more broadly.
Genome-Wide Identification and Comparative Analysis of ARF Family Genes in Three Apiaceae Species
Authors: Pei Qiaoying , Li Nan , Yang Qihang , Wu Tong , Feng Shuyan , Feng Xuehuan , Jing Zange , Zhou Rong , Gong Ke , Yu Tong , Wang Zhen , Song Xiaoming
Published: January 2021

The family Apiaceae includes many important vegetables and medicinal plants. Auxin response factors (ARFs) play critical roles in regulating plant growth and development. Here, we performed a comprehensive analysis of the ARF gene family in three Apiaceae species, celery, coriander, and carrot, and compared the results with the ARF gene family of lettuce, Arabidopsis, and grape. We identified 156 ARF genes in all six species and 89 genes in the three Apiaceae species, including 28, 34, and 27 in celery, coriander, and carrot, respectively. The paralogous gene number in coriander was far greater than that in carrot and celery. Our analysis revealed that ARF genes of the three Apiaceae species in 34 branches of the phylogenetic tree underwent significant positive selection. Additionally, our findings indicated that whole-genome duplication played an important role in ARF gene family expansion. Coriander contained a greater number of ARF genes than celery and carrot because of more gene duplications and less gene losses. We also analyzed the expression of ARF genes in three tissues by RNA-seq and verified the results by quantitative real-time PCR. Furthermore, we found that several paralogous genes exhibited divergent expression patterns. Overall, this study provides a valuable resource for exploring how ARF family genes regulate plant growth and development in other plants. Since this is the first report of the ARF gene family in Apiaceae, our results will serve as a guide for comparative and functional analyses of ARF and other gene families in Apiaceae.
The Functional Impact of Alternative Splicing on the Survival Prognosis of Triple-Negative Breast Cancer
Authors: Wu Sijia , Wang Jiachen , Zhu Xinchao , Chyr Jacqueline , Zhou Xiaobo , Wu Xiaoming , Huang Liyu
Published: January 2021

Purpose

Triple-negative breast cancer (TNBC) is a type of breast cancer (BC) showing a high recurrence ratio and a low survival probability, which requires novel actionable molecular targets. The involvement of alternative splicing (AS) in TNBC promoted us to study the potential roles of AS events in the survival prognosis of TNBC patients.

Methods

A total of 150 TNBC patients from The Cancer Genome Atlas (TCGA) were involved in this work. To study the effects of AS in the recurrence-free survival (RFS) prognosis of TNBC, we performed the analyses as follows. First, univariate Cox regression model was applied to identify RFS-related AS events. Their host genes were analyzed by Metascape to discover the potential functions and involved pathways. Next, least absolute shrinkage and selection operator (LASSO) method was used to select the most informative RFS-related AS events to constitute an AS risk factor for RFS prognosis, which was evaluated by Kaplan–Meier (KM) and receiver operating characteristic (ROC) curves in all the data and also in different clinical subgroups. Furthermore, we analyzed the relationships between splicing factors (SFs) and these RFS-related AS events to seek the possibility that SFs regulated AS events to influence RFS. Then, we evaluated the potential of these RFS-related AS events in the overall survival (OS) prognosis from all the above aspects.

Results

We identified a total of 546 RFS-related AS events, which were enriched in some splicing and TNBC-associated pathways. Among them, seven RFS-related events were integrated into a risk factor, exhibiting satisfactory RFS prognosis alone and even better performance when combined with clinical tumor–node–metastasis stages. Furthermore, the correlation analysis between SFs and the seven AS events revealed the hypotheses that SRPK3 might upregulate PCYT2_44231_AA to have an effect on RFS prognosis and that three other SFs may work together to downregulate FLAD1_7874_RI to influence RFS prognosis. In addition, the seven RFS-related AS events were validated to be promising in the OS prognosis of TNBC as well.

Conclusion

The abnormal AS events regulated by SFs may act as a kind of biomarker for the survival prognosis of TNBC.
Does Angiotensin II Peak in Response to SARS-CoV-2?
Authors: Xavier Léder Leal , Neves Paula Fernanda Ribas , Paz Lisiê Valeria , Neves Laura Tartari , Bagatini Pamela Brambilla , Timmers Luís Fernando Saraiva Macedo , Rasia-Filho Alberto Antônio , Mestriner Régis Gemerasca , Wieck Andrea
Published: January 2021

Human infection by the SARS-CoV-2 is causing the current COVID-19 pandemic. With the growing numbers of cases and deaths, there is an urgent need to explore pathophysiological hypotheses in an attempt to better understand the factors determining the course of the disease. Here, we hypothesize that COVID-19 severity and its symptoms could be related to transmembrane and soluble Angiotensin-converting enzyme 2 (tACE2 and sACE2); Angiotensin II (ANG II); Angiotensin 1-7 (ANG 1-7) and angiotensin receptor 1 (AT1R) activation levels. Additionally, we hypothesize that an early peak in ANG II and ADAM-17 might represent a physiological attempt to reduce viral infection via tACE2. This viewpoint presents: (1) a brief introduction regarding the renin-angiotensin-aldosterone system (RAAS), detailing its receptors, molecular synthesis, and degradation routes; (2) a description of the proposed early changes in the RAAS in response to SARS-CoV-2 infection, including biological scenarios for the best and worst prognoses; and (3) the physiological pathways and reasoning for changes in the RAAS following SARS-CoV-2 infection.
A Population of Radio-Resistant Macrophages in the Deep Myenteric Plexus Contributes to Postoperative Ileus Via Toll-Like Receptor 3 Signaling
Authors: Enderes Jana , Mallesh Shilpashree , Schneider Reiner , Hupa Kristof J. , Lysson Mariola , Schneiker Bianca , Händler Kristian , Schlotmann Balthasar , Günther Patrick , Schultze Joachim L. , Kalff Jörg C. , Wehner Sven
Published: January 2021

Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter’s contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter-inducing interferon-β (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-β reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit and leukocyte extravasation into the ME. TRIF/TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.
Peripheral Immune Cell Ratios and Clinical Outcomes in Seropositive Autoimmune Encephalitis: A Study by the Australian Autoimmune Encephalitis Consortium
Authors: Broadley James , Wesselingh Robb , Seneviratne Udaya , Kyndt Chris , Beech Paul , Buzzard Katherine , Nesbitt Cassie , D’Souza Wendyl , Brodtmann Amy , Kalincik Tomas , Butzkueven Helmut , O’Brien Terence J. , Monif Mastura ,   Australian Autoimmune Encephalitis Consortium
Published: January 2021

Objective

To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE).

Methods

In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissions between January 2008 and June 2019. The initial full blood examination was used to determine each patients’ NLR and MLR. The modified Rankin Scale (mRS) was utilized to assess the patients’ follow-up disability at 12 months and then at final follow-up. Primary outcomes were mortality and mRS, while secondary outcomes were failure of first line treatment, ICU admission, and clinical relapse. Univariate and multivariable regression analysis was performed.

Results

During initial hospital admission 44.7% of patients had unsuccessful first line treatment. After a median follow-up of 700 days, 82.7% had good functional outcome (mRS ≤2) while five patients had died. On multivariable analysis, high NLR was associated with higher odds of first line treatment failure (OR 1.32, 95% CI 1.03–1.69, p = 0.029). Increased MLR was not associated with any short or long-term outcome.

Conclusions

NLR on initial hospital admission blood tests may be provide important prognostic information for cases of seropositive AE. This study demonstrates the potential use of NLR as a prognostic marker in the clinical evaluation of patients with seropositive AE.
Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury
Authors: Li Xiangyun , Berg Nathanial K. , Mills Tingting , Zhang Kaiying , Eltzschig Holger K. , Yuan Xiaoyi
Published: January 2021

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine signaling to inhibit the inflammatory response in ARDS, while in chronic lung diseases, it promotes inflammation and tissue injury. In this review, we discuss the role of adenosine at the interphase of hypoxia and inflammation in ARDS and chronic lung diseases, as well as the current strategy for therapeutic targeting of the adenosine signaling pathway.
CCR2- and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01
Authors: Bosteels Cedric , Fierens Kaat , De Prijck Sofie , Van Moorleghem Justine , Vanheerswynghels Manon , De Wolf Caroline , Chalon Aurélie , Collignon Catherine , Hammad Hamida , Didierlaurent Arnaud M. , Lambrecht Bart N.
Published: January 2021

The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of adaptive immunity by AS01 is highly dependent on the ability to recruit and activate dendritic cells (DCs) that migrate to the draining lymph node for T and B cell stimulation. The objective of this study was to more precisely address the contribution of the different conventional (cDC) and monocyte-derived DC (MC) subsets in the orchestration of the adaptive immune response after immunization with AS01 adjuvanted vaccine. The combination of MPL and QS-21 in AS01 induced strong recruitment of CD26+XCR1+ cDC1s, CD26+CD172+ cDC2s and a recently defined CCR2-dependent CD64-expressing inflammatory cDC2 (inf-cDC2) subset to the draining lymph node compared to antigen alone, while CD26-CD64+CD88+ MCs were barely detectable. At 24 h post-vaccination, cDC2s and inf-cDC2s were superior amongst the different subsets in priming antigen-specific CD4+ T cells, while simultaneously presenting antigen to CD8+ T cells. Diphtheria toxin (DT) mediated depletion of all DCs prior to vaccination completely abolished adaptive immune responses, while depletion 24 h after vaccination mainly affected CD8+ T cell responses. Vaccinated mice lacking Flt3 or the chemokine receptor CCR2 showed a marked deficit in inf-cDC2 recruitment and failed to raise proper antibody and T cell responses. Thus, the adjuvant activity of AS01 is associated with the potent activation of subsets of cDC2s, including the newly described inf-cDC2s.
Glycoproteoform Profiles of Individual Patients’ Plasma Alpha-1-Antichymotrypsin are Unique and Extensively Remodeled Following a Septic Episode
Authors: Čaval Tomislav , Lin Yu-Hsien , Varkila Meri , Reiding Karli R. , Bonten Marc J. M. , Cremer Olaf L. , Franc Vojtech , Heck Albert J. R.
Published: January 2021

Sepsis and septic shock remain the leading causes of death in intensive care units (ICUs), yet the pathogenesis originating from the inflammatory response during sepsis remains ambiguous. Acute-phase proteins are typically highly glycosylated, and the nature of the glycans have been linked to the incidence and severity of such inflammatory responses. To further build upon these findings we here monitored, the longitudinal changes in the plasma proteome and, in molecular detail, glycoproteoform profiles of alpha-1-antichymotrypsin (AACT) extracted from plasma of ten individual septic patients. For each patient we included four different time-points, including post-operative (before sepsis) and following discharge from the ICU. We isolated AACT from plasma depleted for albumin, IgG and serotransferrin and used high-resolution native mass spectrometry to qualitatively and quantitatively monitor the multifaceted glycan microheterogeneity of desialylated AACT, which allowed us to monitor how changes in the glycoproteoform profiles reflected the patient’s physiological state. Although we observed a general trend in the remodeling of the AACT glycoproteoform profiles, e.g. increased fucosylation and branching/LacNAc elongation, each patient exhibited unique features and responses, providing a resilient proof-of-concept for the importance of personalized longitudinal glycoproteoform profiling. Importantly, we observed that the AACT glycoproteoform changes induced by sepsis did not readily subside after discharge from ICU.
Non-Epithelial Thymic Stromal Cells: Unsung Heroes in Thymus Organogenesis and T Cell Development
Authors: Nitta Takeshi , Takayanagi Hiroshi
Published: January 2021

The stromal microenvironment in the thymus is essential for generating a functional T cell repertoire. Thymic epithelial cells (TECs) are numerically and phenotypically one of the most prominent stromal cell types in the thymus, and have been recognized as one of most unusual cell types in the body by virtue of their unique functions in the course of the positive and negative selection of developing T cells. In addition to TECs, there are other stromal cell types of mesenchymal origin, such as fibroblasts and endothelial cells. These mesenchymal stromal cells are not only components of the parenchymal and vascular architecture, but also have a pivotal role in controlling TEC development, although their functions have been less extensively explored than TECs. Here, we review both the historical studies on and recent advances in our understanding of the contribution of such non-TEC stromal cells to thymic organogenesis and T cell development. In particular, we highlight the recently discovered functional effect of thymic fibroblasts on T cell repertoire selection.