bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeless Micropayments as Drivers for New Business Models: Two Exemplary Application Cases
Authors: Klein Marvin , Stummer Christian
Published: March 2021

Upcoming cryptocurrency approaches claim to enable feeless micropayments. Assuming that this promise will be kept, this is likely to give rise to new business models that entail transactions worth fractions of a cent. In this mini review, we describe two exemplary application cases and outline the associated research activities for each. The first case considers subscription models in consumer markets for which feeless micropayments might be used to expand and, thus, enrich the range of plans by offering shorter subscription times. The second case is concerned with prosumers who might be willing to sell self-generated data (e.g., data generated through their smart meters).
Crescent-Moon Beam-To-Column Connection for Precast Industrial Buildings
Authors: Bressanelli Michele Egidio , Bosio Marco , Belleri Andrea , Riva Paolo , Biagiotti Piergiovanni
Published: March 2021

The 2012 Emilia earthquakes caused significant damage to existing precast reinforced concrete (RC) industrial buildings not specifically designed to resist seismic actions. The main failure mechanisms were related to the loss of support of beams and roof elements caused by high relative displacements, to the failure of the mechanical connections and consequent fall of cladding panels, to the damage at the base of the columns and to the collapse of RC forks at the top of the columns. In all cases, the behavior of the connections, and specifically of beam-to-column connections, demonstrated to be crucial, given that they may inhibit the exploitation of strength and ductility reserves in precast elements. This paper presents a beam-to-column connection restraint-device for precast industrial buildings. The device can be applied to existing structures to transfer horizontal seismic forces between beams and columns and to increase the energy dissipation of the system. Design criteria were defined with the aim to limit the relative maximum displacement at the beam-to-column interface and to mitigate the out-of-plane overturning of the beam. Numerical analyses were carried out to define a suitable shape of the device and to investigate its effectiveness in terms of both local and global behavior. To validate the computational results, experimental tests have been also carried out. The tests allowed to classify the device as “dissipative” according to UNI EN 15129. Finally, the design procedure has been validated considering a one-story industrial building case study designed in accordance with the Italian building code.
Estimation of Ground Profiles Based on Microtremor Survey in the Bangkok Basin
Authors: Subedi Bidhya , Kiyono Junji , Furukawa Aiko , Ono Yusuke , Ornthammarath Teraphan , Kitaoka Takafumi , Charatpangoon Bhuddarak , Latcharote Panon
Published: March 2021

Multiple earthquakes have been felt in high-rise buildings in Bangkok despite the epicenters being far away. Seismic wave recordings in the Bangkok basin show a low-frequency peak. This study uses horizontal-to-vertical spectral ratio (HVSR) analysis and array analysis of ambient vibration data to find the predominant period of the ground and the shear wave velocity profiles at five sites in Bangkok. The accuracy of the accelerometer used for the ambient data recording was verified by comparing results with velocity-meter results. The estimated predominant period was within 0.68–0.86 s. From the array records, dispersion curves of the Rayleigh-wave phase velocity were extracted and inverted for the deep layers. The results show that the shear-wave velocity of the top clay layer is low (82–120 m/s) at depths of 11–14.3 m. The low-frequency peak in the HVSR of the earthquake data, and the sediment layer with low shear-wave velocity implies that Bangkok is at risk of amplification of long-period earthquake waves.
BRG1 Links TLR4 Trans-Activation to LPS-Induced SREBP1a Expression and Liver Injury
Authors: Dong Wenhui , Zhu Yuwen , Zhang Yangxi , Fan Zhiwen , Zhang Ziyu , Fan Xiangshan , Xu Yong
Published: March 2021

Multiple organ failure is one of the most severe consequences in patients with septic shock. Liver injury is frequently observed during this pathophysiological process. In the present study we investigated the contribution of Brahma related gene 1 (BRG1), a chromatin remodeling protein, to septic shock induced liver injury. When wild type (WT) and liver conditional BRG1 knockout (LKO) mice were injected with lipopolysaccharide (LPS), liver injury was appreciably attenuated in the LKO mice compared to the WT mice as evidenced by plasma ALT/AST levels, hepatic inflammation and apoptosis. Of interest, there was a down-regulation of sterol response element binding protein 1a (SREBP1a), known to promote liver injury, in the LKO livers compared to the WT livers. BRG1 did not directly bind to the SREBP1a promoter. Instead, BRG1 was recruited to the toll-like receptor 4 (TLR4) promoter and activated TLR4 transcription. Ectopic TLR4 restored SREBP1a expression in BRG1-null hepatocytes. Congruently, adenovirus carrying TLR4 or SREBP1a expression vector normalized liver injury in BRG1 LKO mice injected with LPS. Finally, a positive correlation between BRG1 and TLR4 expression was detected in human liver biopsy specimens. In conclusion, our data demonstrate that a BRG1-TLR4-SREBP1a axis that mediates LPS-induced liver injury in mice.
Assessing the Regulatory Functions of LncRNA SNHG11 in Gastric Cancer Cell Proliferation and Migration
Authors: Zhao Danyi , Chen Huawei , Wang Bing
Published: March 2021

The aim of this study was to assess the regulatory functions of SNHG11 in gastric cancer (GC) cell proliferation and migration. Dual-luciferase reporter assay and bioinformatics prediction [starBase (http://starbase.sysu.edu.cn/) and TargetScan (http://www.targetscan.org)] indicated that SNHG11 functions as a miR-184 sponge that can directly act on CDC25A. Compared with normal healthy gastric tissue and mucosal epithelial cell GES-1, SNHG11 and CDC25A expressions were dramatically increased in GC samples and cell lines, whereas microRNA-184 (miR-184) levels were reduced. SNHG11 silencing led to increased miR-184 and reduced CDC25A, whereas miR-184 downregulation recovered the expression of CDC25A. Additionally, miR-184 upregulation also played a role in regulating CDC25A ablation. Then, SNHG11 was silenced or miR-184 was upregulated in two GC cells (SGC-7901 and MKN-28). SNHG11 silencing and miR-184 upregulation caused a notable decrease in GC cell growth and proliferation and increased the apoptotic level of GC cells. Furthermore, SNHG11 silencing and miR-184 upregulation contributed to a decreased migration capacity of GC cells. Downregulated miR-184 expression in SNHG11 silenced GC cells showed that miR-184 inhibition reversed the effect of SNHG11 silencing on the growth, proliferation, apoptosis, and migration of GC cells. Moreover, in vivo xenograft experiments demonstrated that SNHG11 knockdown can inhibit tumor growth. These observations confirmed that SNHG11 acts as an oncogene, whereas miR-194 served as a tumor suppressor in GC development. SNHG11 may provide a new biomarker for GC diagnosis, treatment, and prognosis.
Bacterial Behavior in Confined Spaces
Authors: Du Hang , Xu Weili , Zhang Zhizhou , Han Xiaojun
Published: March 2021

In confined spaces, bacteria exhibit unexpected cellular behaviors that are related to the biogeochemical cycle and human health. Types of confined spaces include lipid vesicles, polymer vesicles, emulsion droplets, microfluidic chips, and various laboratory-made chambers. This mini-review summarizes the behaviors of living bacteria in these confined spaces, including (a) growth and proliferation, (b) cell communication, and (c) motion. Future trends and challenges are also discussed in this paper.
Changes in the Human Gut Microbiota Associated With Colonization by Blastocystis sp. and Entamoeba spp. in Non-Industrialized Populations
Authors: Even Gaël , Lokmer Ana , Rodrigues Jules , Audebert Christophe , Viscogliosi Eric , Ségurel Laure , Chabé Magali
Published: March 2021

Human gut microbial communities are mainly composed of bacteria, but also include fungi, viruses, archaea, and protozoa, whose role in the gut ecosystem has only recently begun to be recognized. For example, humans colonized by Blastocystis (a gut protozoan with controversial pathogenicity) host a more diverse bacterial microbiota than individuals not carrying it, suggesting that its presence may be beneficial for the host. In parallel, the presence of non-pathogenic Entamoeba spp. has been associated with an increased diversity and compositional shifts in the bacterial microbiota of healthy rural individuals in Cameroon. However, Entamoeba and Blastocystis, the two most prevalent human gut protozoa, have never been studied in the same individuals, preventing the study of their interaction. As Blastocystis is one of the few gut protozoa commonly found in industrialized populations, which are otherwise mostly devoid of gut eukaryotes, we need to focus on rural “traditional” populations, who harbor a higher diversity of gut eukaryotes (whether pathogenic or commensal) in order to study protozoa interactions in the gut ecosystem. To this end, we profiled the gut bacterial microbiota of 134 healthy Cameroonian adults using 16S rRNA gene amplicon sequencing data. Entamoeba and Blastocystis presence and co-occurrence pattern in the same individuals were determined using metagenomic shotgun data. We found that, when taking into account both protozoa jointly, Blastocystis was associated with both a higher richness and a higher evenness of the gut bacterial microbiota, while Entamoeba was associated only with a higher richness. We demonstrated a cumulative influence of these protozoa on bacterial microbiome diversity. Furthermore, while the abundance of several common taxa (for example, Ruminococcaceae, Coprococcus and Butyrivibrio) varied according to Blastocystis colonization, only a single Bacteroides amplicon sequence variant was found to be differentially abundant between Entamoeba-negative and Entamoeba-positive samples. Given the specific signature of each protozoan on the gut microbiota and the seemingly stronger association for Blastocystis, our results suggest that Blastocystis and Entamoeba interact with gut bacteria each in its own way, but experimental studies are needed to explore the precise mechanisms of these interactions.
Exploring the Adaptive Capacity of Sugarcane Contract Farming Schemes in the Face of Extreme Events
Authors: Henriksson Rebecka , Vincent Katharine , Naidoo Kivana
Published: March 2021

Adaptive capacity determines the extent to which exposure to natural hazards and extreme events translates into impacts. This study traces the effectiveness of adaptive capacity of two different sugarcane contract farming schemes (so-called outgrower schemes)—Phata and Kasinthula—in Chikwawa district in southern Malawi which, due to their proximity, are similarly exposed to extreme events, but have shown different impacts in terms of sugarcane production. We develop a framework to explore and compare the adaptive capacity at scheme management level, and relate the findings to the historical changes in yield, the occurrence of extreme events in the district and the lived experiences of the scheme management over the last ten years (2010–2019) using qualitative data from interviews with scheme managers. The total level and components of adaptive capacity differ in several aspects. Phata had much better prerequisites to mitigate the impacts of the extreme events (i.e., maintain production), particularly related to the Asset base, Knowledge and information, Innovation, and Forward-looking decision-making. Kasinthula on the other hand, was impacted by compound events whilst having low financial capacity, weak governance and reduced human capacity. Kasinthula had limited capacity to recover from the severe 2015 floods, the adaptive capacity thus drawn upon and were not restored when next event occurred (drought). This novel, comparative approach to assessing adaptive capacity, linking to past events, has been shown useful in order to determine the components that are missing and need to be built in order to reduce risk from extreme events and climate change. These findings are important to ensure future adaptation of sugarcane outgrowers, and relevant also to other contract farming arrangements or similar kinds of agricultural organizations.
Mapping Micro-Level Decision-Making for Alligator Management in North Carolina
Authors: Cavalier Rebecca , Serenari Christopher , Konur Dinçer
Published: March 2021

Human-carnivore interactions represent a grand challenge to conservation decision-making and legitimacy across all levels of governance. Human populations continue to encroach upon and devastate carnivore habitats and populations, intensifying interactions between a variety of biodiversity interests and beneficiaries. As a result, carnivores most intensely impact those living in their midst, demanding increased attention by local decision makers, who are often best suited to catering to the needs of communities most affected. Their views and desires can serve as a forerunner of public trust and acceptance of policies created. However, due to the complexity of decisions about carnivores, these actors are often overlooked in the formal decision process. To address this need, we applied multi-criteria decision analysis (MCDA) to a case study of American alligator (Alligator mississippiensis) conservation in 10 coastal North Carolina counties to identify and postulate legitimate outcomes. We surveyed 25 local decision makers who are or may be responsible for management decisions concerning the American alligator and asked them to evaluate and indicate the level of importance of salient alligator management elements. Results indicate that decision makers strongly favored the wildlife and social factors when making alligator management decisions, as well as the criteria human well-being, attitudes toward alligators, education programs, and storm mitigation. Respondents favored highly managed and balanced management alternatives to maximize preferred criteria and achieve legitimate alligator management at the local level. These results demonstrate that local decision makers are capable of identifying what is important to alligator management decisions, and can provide an insightful look at trade-offs that need to or could be made to achieve optimal alligator outcomes. We conclude that local decision makers should become more involved in shaping carnivore outcomes to enhance legitimacy of alligator policy and help achieve conservation targets. Future research will need to further expand understandings of local decision makers' decision-making process in other carnivore contexts. Researchers will want to consider using and refining decision analysis to cut through the complexity of carnivore conservation decision-making that exists across wide geopolitical expanses.
Italian Tsunami Effects Database (ITED): The First Database of Tsunami Effects Observed Along the Italian Coasts
Authors: Maramai Alessandra , Graziani Laura , Brizuela Beatriz
Published: March 2021

Traditional tsunami catalogues are conceived as a collection of tsunamis classified by the generating cause, providing a general description of the effects observed for each tsunami. Those catalogues, even if they provide fundamental information, are not suitable for producing an exhaustive picture of the geographical distribution of the tsunami effects. In this paper we introduce the new Italian Tsunami Effects Database (ITED), a collection of evidence documenting the effects along the Italian coasts from historical times to present. The database comes forth the Euro-Mediterranean Tsunami Catalogue (EMTC) and focusses on the effects of tsunamis observed along the Italian coasts providing descriptive and quantitative information for each OP. The information reported in ITED does not only concern the effects produced by Italian tsunamis, but also those effects produced by tsunamis originated outside the Italian territory. ITED contains 318 OPs, related to 73 Italian tsunamis and to four tsunamis which occurred outside Italy. The database can be accessed through a WebApp that displays for each OP the description of effects, quantitative data (run-up, inundation, withdrawal, etc.) and tsunami intensity with the corresponding bibliographic references. The database also provides the tsunami intensity distribution along time (tsunami-history) for each site, allowing the end user to know how a place has been affected by tsunamis over the time. The information contained in ITED makes this database a useful tool to understand how tsunamis have affected the Italian territory and emphasizes the importance of studying the tsunami hazard along the Italian coasts.
Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease
Authors: Akirov Amit , Larouche Vincent , Shimon Ilan , Asa Sylvia L. , Mete Ozgur , Sawka Anna M. , Gentili Fred , Ezzat Shereen
Published: March 2021

Background

Glucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD.

Methods

The retrospective chart review study included patients with clinical, biochemical, radiologic and outcome data and evaluable histopathology specimens from pituitary surgery for CD. The main outcome was remission of CD, defined by clinical features, biochemical testing, and corticosteroid dependency.

Results

Of 144 CD patients, 60 (50 women, mean age 43.6±14) had clinical follow-up, biochemical data and histopathology specimens that included evaluable nontumorous adenohypophysis. Specimens from 50 patients (83.3%) demonstrated CC in nontumorous corticotrophs, and 10 (16.7%) had no CC (including 3 with corticotroph hyperplasia). One patient with CC was lost to follow-up and one without CC had equivocal outcome results. During a mean (SD) follow-up period of 74.9 months (61.0), recurrent or persistent disease was documented in 18 patients (31.0%), while 40 (69.0%) were in remission. In patients with CC, the remission rate was 73.5% (95% CI, 59.7%-83.7%) (36/49), whereas it was 44.4% (95% CI, 18.9%-73.3%) (4/9) in patients with no CC. The combination of serum cortisol >138 nmol/L within a week of surgery coupled with absence of nontumorous CC greatly improved the prediction of recurrent or persistent disease.

Conclusions

CC of nontumorous corticotrophs was observed in 83% of patients with CD, and most patients with CC experienced remission. Absence of CC in nontumorous corticotrophs may serve as a predictor of reduced remission in patients with CD.
Landscape-Scale Effects of Irrigation on a Dry Cereal Farmland Bird Community
Authors: Giralt David , Pantoja Javiera , Morales Manuel B. , Traba Juan , Bota Gerard
Published: March 2021

Landscape modification and habitat fragmentation are one of the major current threats to biodiversity. The main source of habitat fragmentation is the loss of focal habitat area, but changes in the composition of the surrounding landscape also have a direct effect on biodiversity. These changes may lead to the loss of some species but also may favor species replacement. Farmland birds in Europe are affected by landscape changes due to farmland intensification, such as the spread of irrigation, which may occur at different spatial scales. As irrigation is expected to increase in the coming years, which may affect protected areas, it is necessary to evaluate its potential consequences over focal biodiversity. In this study we assess the relationship between the increase of irrigated land at different spatial scales and changes in a dry cereal farmland bird community, bird abundance and species richness, using generalized linear models. We used a dry cereal farmland affinity index to describe the level of community specificity for dry cereal farmland. The increase in irrigated tree orchards produced an increase in species richness up to 500 m away from the irrigated area, which had a negative effect on the dry cereal farmland bird community, by triggering a replacement of specialist by generalist species. Our results show the importance of landscape-scale effects of irrigation occurring outside protected areas on the farmland bird community inside Natura 2000 sites, as well as how these effects are detected even at long distances from the disturbance source.
Estimation of Traffic Flow Rate With Data From Connected-Automated Vehicles Using Bayesian Inference and Deep Learning
Authors: Han Youngjun , Ahn Soyoung
Published: March 2021

Connected automated vehicles (CAVs) hold promise to replace current traffic detection systems in the near future. However, traffic state estimation, particularly flow rate, poses a major challenge at low CAV penetration rates without other supporting infrastructure of sensors. This paper proposes flow rate estimation methods using headway data from CAVs. Specifically, Bayesian inference and deep learning based methods are developed and compared with a naïve method based on a simple arithmetic mean of observed headways. The proposed methods are investigated via numerical experiments to evaluate their performance with respect to the CAV penetration rate, traffic demand, and availability of historical data. The methods are further validated with real data. The results show that the Bayesian inference based method, which estimates the flow rate distribution by integrating current (real-time) data and previous knowledge, can perform well even at low penetration rates with good prior information. However, in high CAV penetration, its relative advantage to the other methods diminishes because the prior information always influences the flow rate estimation. The deep learning based method can be effective with a large amount of data to train the model; however, in low CAV penetration, it tends to converge to the mean of target output values regardless of the observed data. At last, in relatively high CAV penetration, the relative advantage of the advanced methods is negligible and in fact, the naïve method is preferred in terms of accuracy as well as efficiency.
stLFRsv: A Germline Structural Variant Analysis Pipeline Using Co-barcoded Reads
Authors: Guo Junfu , Shi Chang , Chen Xi , Wang Ou , Liu Ping , Yang Huanming , Xu Xun , Zhang Wenwei , Zhu Hongmei
Published: March 2021

Co-barcoded reads originating from long DNA fragments (mean length >30 kbp) maintain both single base level accuracy and long-range genomic information. We propose a pipeline, stLFRsv, to detect structural variation using co-barcoded reads. stLFRsv identifies abnormal large gaps between co-barcoded reads to detect potential breakpoints and reconstruct complex structural variants (SVs). Haplotype phasing by co-barcoded reads increases the signal to noise ratio, and barcode sharing profiles are used to filter out false positives. We integrate the short read SV caller smoove for smaller variants with stLFRsv. The integrated pipeline was evaluated on the well-characterized genome HG002/NA24385, and 74.5% precision and a 22.4% recall rate were obtained for deletions. stLFRsv revealed some large variants not included in the benchmark set that were verified by long reads or assembly. For the HG001/NA12878 genome, stLFRsv also achieved the best performance for both resource usage and the detection of large variants. Our work indicates that co-barcoded read technology has the potential to improve genome completeness.
Comprehensive Analysis of APA Events and Their Association With Tumor Microenvironment in Lung Adenocarcinoma
Authors: Zhang Yuchu , Shen Libing , Shi Qili , Zhao Guofang , Wang Fajiu
Published: March 2021

Background

Alternative polyadenylation (APA) is a pervasive posttranscriptional mechanism regulating gene expression. However, the specific dysregulation of APA events and its potential biological or clinical significance in lung adenocarcinoma (LUAD) remain unclear.

Methods

Here, we collected RNA-Seq data from two independent datasets: GSE40419 (n= 146) and The Cancer Genome Atlas (TCGA) LUAD (n= 542). The DaPars algorithm was employed to characterize the APA profiles in tumor and normal samples. Spearman correlation was used to assess the effects of APA regulators on 3′ UTR changes in tumors. The Cox proportional hazard model was used to identify clinically relevant APA events and regulators. We stratified 512 patients with LUAD in the TCGA cohort through consensus clustering based on the expression of APA factors.

Findings

We identified remarkably consistent alternative 3′ UTR isoforms between the two cohorts, most of which were shortened in LUAD. Our analyses further suggested that aberrant usage of proximal polyA sites resulted in escape from miRNA binding, thus increasing gene expression. Notably, we found that the 3′ UTR lengths of the mRNA transcriptome were correlated with the expression levels of APA factors. We further identified that CPSF2 and CPEB3 may serve as key regulators in both datasets. Finally, four LUAD subtypes according to different APA factor expression patterns displayed distinct clinical results and oncogenic features related to tumor microenvironment including immune, metabolic, and hypoxic status.

Interpretation

Our analyses characterize the APA profiles among patients with LUAD and identify two key regulators for APA events in LUAD, CPSF2 and CPEB3, which could serve as the potential prognostic genes in LUAD.
Detection of Genetic Overlap Between Rheumatoid Arthritis and Systemic Lupus Erythematosus Using GWAS Summary Statistics
Authors: Lu Haojie , Zhang Jinhui , Jiang Zhou , Zhang Meng , Wang Ting , Zhao Huashuo , Zeng Ping
Published: March 2021

Background

Clinical and epidemiological studies have suggested systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are comorbidities and common genetic etiologies can partly explain such coexistence. However, shared genetic determinations underlying the two diseases remain largely unknown.

Methods

Our analysis relied on summary statistics available from genome-wide association studies of SLE (N= 23,210) and RA (N= 58,284). We first evaluated the genetic correlation between RA and SLE through the linkage disequilibrium score regression (LDSC). Then, we performed a multiple-tissue eQTL (expression quantitative trait loci) weighted integrative analysis for each of the two diseases and aggregated association evidence across these tissues via the recently proposed harmonic meanP-value (HMP) combination strategy, which can produce a single well-calibratedP-value for correlated test statistics. Afterwards, we conducted the pleiotropy-informed association using conjunction conditional FDR (ccFDR) to identify potential pleiotropic genes associated with both RA and SLE.

Results

We found there existed a significant positive genetic correlation (rg= 0.404,P= 6.01E-10) via LDSC between RA and SLE. Based on the multiple-tissue eQTL weighted integrative analysis and the HMP combination across various tissues, we discovered 14 potential pleiotropic genes by ccFDR, among which four were likely newly novel genes (i.e.,INPP5B,OR5K2,RP11-2C24.5, andCTD-3105H18.4). The SNP effect sizes of these pleiotropic genes were typically positively dependent, with an average correlation of 0.579. Functionally, these genes were implicated in multiple auto-immune relevant pathways such as inositol phosphate metabolic process, membrane and glucagon signaling pathway.

Conclusion

This study reveals common genetic components between RA and SLE and provides candidate associated loci for understanding of molecular mechanism underlying the comorbidity of the two diseases.
Talk Is Silver, Code Is Gold? Beyond Traditional Notions of Contribution in Peer Production: The Case of Drupal
Authors: Rozas David , Gilbert Nigel , Hodkinson Paul , Hassan Samer
Published: March 2021

Peer production communities are based on the collaboration of communities of people, mediated by the Internet, typically to create digital commons, as in Wikipedia or free software. The contribution activities around the creation of such commons (e.g., source code, articles, or documentation) have been widely explored. However, other types of contribution whose focus is directed toward the community have remained significantly less visible (e.g., the organization of events or mentoring). This work challenges the notion of contribution in peer production through an in-depth qualitative study of a prominent “code-centric” example: the case of the free software project Drupal. Involving the collaboration of more than a million participants, the Drupal project supports nearly 2% of websites worldwide. This research (1) offers empirical evidence of the perception of “community-oriented” activities as contributions, and (2) analyzes their lack of visibility in the digital platforms of collaboration. Therefore, through the exploration of a complex and “code-centric” case, this study aims to broaden our understanding of the notion of contribution in peer production communities, incorporating new kinds of contributions customarily left invisible.
Single-Cell Transcriptomic Analyses Define Distinct Peripheral B Cell Subsets and Discrete Development Pathways
Authors: Stewart Alexander , Ng Joseph Chi-Fung , Wallis Gillian , Tsioligka Vasiliki , Fraternali Franca , Dunn-Walters Deborah K.
Published: March 2021

Separation of B cells into different subsets has been useful to understand their different functions in various immune scenarios. In some instances, the subsets defined by phenotypic FACS separation are relatively homogeneous and so establishing the functions associated with them is straightforward. Other subsets, such as the “Double negative” (DN, CD19+CD27-IgD-) population, are more complex with reports of differing functionality which could indicate a heterogeneous population. Recent advances in single-cell techniques enable an alternative route to characterize cells based on their transcriptome. To maximize immunological insight, we need to match prior data from phenotype-based studies with the finer granularity of the single-cell transcriptomic signatures. We also need to be able to define meaningful B cell subsets from single cell analyses performed on PBMCs, where the relative paucity of a B cell signature means that defining B cell subsets within the whole is challenging. Here we provide a reference single-cell dataset based on phenotypically sorted B cells and an unbiased procedure to better classify functional B cell subsets in the peripheral blood, particularly useful in establishing a baseline cellular landscape and in extracting significant changes with respect to this baseline from single-cell datasets. We find 10 different clusters of B cells and applied a novel, geometry-inspired, method to RNA velocity estimates in order to evaluate the dynamic transitions between B cell clusters. This indicated the presence of two main developmental branches of memory B cells. A T-independent branch that involves IgM memory cells and two DN subpopulations, culminating in a population thought to be associated with Age related B cells and the extrafollicular response. The other, T-dependent, branch involves a third DN cluster which appears to be a precursor of classical memory cells. In addition, we identify a novel DN4 population, which is IgE rich and closely linked to the classical/precursor memory branch suggesting an IgE specific T-dependent cell population.
Efficacy and Effect of Inhaled Adenosine Treatment in Hospitalized COVID-19 Patients
Authors: Caracciolo Massimo , Correale Pierpaolo , Mangano Carmelo , Foti Giuseppe , Falcone Carmela , Macheda Sebastiano , Cuzzola Maria , Conte Marco , Falzea Antonella Consuelo , Iuliano Eleonora , Morabito Antonella , Caraglia Michele , Polimeni Nicola , Ferrarelli Anna , Labate Demetrio , Tescione Marco , Di Renzo Laura , Chiricolo Gaetano , Romano Lorenzo , De Lorenzo Antonino
Published: March 2021

Lack of specific antiviral treatment for COVID-19 has resulted in long hospitalizations and high mortality rate. By harnessing the regulatory effects of adenosine on inflammatory mediators, we have instituted a new therapeutic treatment with inhaled adenosine in COVID-19 patients, with the aim of reducing inflammation, the onset of cytokine storm, and therefore to improve prognosis. The use of inhaled adenosine in COVID19 patients has allowed reduction of length of stay, on average 6 days. This result is strengthened by the decrease in SARS-CoV-2 positive days. In treated patients compared to control, a clear improvement in PaO2/FiO2was observed together with a reduction in inflammation parameters, such as the decrease of CRP level. Furthermore, the efficacy of inhaled exogenous adenosine led to an improvement of the prognosis indices, NLR and PLR. The treatment seems to be safe and modulates the immune system, allowing an effective response against the viral infection progression, reducing length of stay and inflammation parameters.
Adiponectin Enhances B-Cell Proliferation and Differentiation via Activation of Akt1/STAT3 and Exacerbates Collagen-Induced Arthritis
Authors: Che Nan , Sun Xiaoxuan , Gu Lei , Wang Xiaohui , Shi Jingjing , Sun Yi , Xu Lingxiao , Liu Rui , Wang Junke , Zhu Fengyi , Peng Na , Xiao Fan , Hu Dajun , Lu Liwei , Qiu Wen , Zhang Miaojia
Published: March 2021

Although B cells have been shown to contribute to the pathogenesis of rheumatoid arthritis (RA), the precise role of B cells in RA needs to be explored further. Our previous studies have revealed that adiponectin (AD) is expressed at high levels in inflamed synovial joint tissues, and its expression is closely correlated with progressive bone erosion in patients with RA. In this study, we investigated the possible role of AD in B cell proliferation and differentiation. We found that AD stimulation could induce B cell proliferation and differentiation in cell culture. Notably, local intraarticular injection of AD promoted B cell expansion in joint tissues and exacerbated arthritis in mice with collagen-induced arthritis (CIA). Mechanistically, AD induced the activation of PI3K/Akt1 and STAT3 and promoted the proliferation and differentiation of B cells. Moreover, STAT3 bound to the promoter of the Blimp-1 gene, upregulated Blimp-1 expression at the transcriptional level, and promoted B cell differentiation. Collectively, we observed that AD exacerbated CIA by enhancing B cell proliferation and differentiation mediated by the PI3K/Akt1/STAT3 axis.
Characterization of Coelomic Fluid Cell Types in the Starfish Marthasterias glacialis Using a Flow Cytometry/Imaging Combined Approach
Authors: Andrade Claúdia , Oliveira Bárbara , Guatelli Silvia , Martinez Pedro , Simões Beatriz , Bispo Claúdia , Ferrario Cinzia , Bonasoro Francesco , Rino José , Sugni Michela , Gardner Rui , Zilhão Rita , Coelho Ana Varela
Published: March 2021

Coelomocytes is the generic name for a collection of cellular morphotypes, present in many coelomate animals, and highly variable among echinoderm classes. The roles attributed to the major types of these free circulating cells present in the coelomic fluid of echinoderms include immune response, phagocytic digestion and clotting. Our main aim in this study was to characterize coelomocytes found in the coelomic fluid ofMarthasterias glacialis(class Asteroidea) by using a combination of flow cytometry (FC), imaging flow cytometry (IFC) and fluorescence plus transmission electron microscopy (TEM). Two coelomocyte populations (P1 and P2) identified through flow cytometry were subsequently studied in terms of abundance, morphology, ultrastructure, cell viability and cell cycle profiles. Ultrastructurally, P2 diploid cells were present as two main morphotypes, similar to phagocytes and vertebrate thrombocytes, whereas the smaller P1 cellular population was characterized by low mitotic activity, a relatively undifferentiated cytotype and a high nucleus/cytoplasm ratio. In the present study we could not rule out possible similarities between haploid P1 cells and stem-cell types in other animals. Additionally, we report the presence of two other morphotypes in P2 that could only be detected by fluorescence microscopy, as well as a morphotype revealedviacombined microscopy/FC. This integrative experimental workflow combined cells physical separation with different microscopic image capture technologies, enabling us to better tackle the characterization of the heterogeneous composition of coelomocytes populations.
Physical and Biogeochemical Regionalization of the Southern Ocean and the CCAMLR Zone 48.1
Authors: Testa Giovanni , Piñones Andrea , Castro Leonardo R.
Published: March 2021

The Southern Ocean plays a major role in the Earth’s climate, provides fisheries products and help the maintenance of biodiversity. The degree of correspondence between physical and biogeochemical spatial variability and regionalization were investigated by calculating the main physical factors that statistically explained the biogeochemical variability within the Southern Ocean and the 48.1 zone of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR). The mean value of physical and biogeochemical variables was estimated during austral summer within a grid of 1° × 1° south of 50°S. The regionalization was developed using both non-hierarchical and hierarchical clustering method, whereas BIO-ENV package and distance-based redundancy analysis (db-RDA) were applied in order to calculate which physical factors primarily explained the biogeochemical spatial variability. A total of 12 physical and 18 biogeochemical significant clusters were identified for the Southern Ocean (alpha: 0.05). The combination of bathymetry and sea ice coverage majorly explained biogeochemical variability (Spearman rank correlation coefficient: 0.68) and db-RDA indicated that physical variables expressed the 60.1% of biogeochemical variance. On the other hand, 14 physical and 16 biogeochemical significant clusters were identified for 48.1 CCAMLR zone. Bathymetry was the main factor explaining biogeochemical variability (Spearman coefficient: 0.81) and db-RDA analysis resulted in 77.1% of biogeochemical variance. The correspondence between physical and biogeochemical regions was higher for CCAMLR 48.1 zone with respect to the whole Southern Ocean. Our results provide useful information for both Southern Ocean and CCAMLR 48.1 zone ecosystem management and modeling parametrization.
Scenario-Based Approaches to Change Management in Fisheries Can Address Challenges With Scale and Support the Implementation of an Ecosystem Approach to Fisheries Management
Authors: Gammage Louise Carin , Jarre Astrid
Published: March 2021

The Ecosystem Approach to Fisheries (EAF) management, recognising complexity, aims for the holistic, sustainable management of fisheries to promote healthy marine ecosystems and sustainable livelihoods. Effective implementation of the EAF has been problematic as we continue to grapple with issues of scale, knowledge integration and meaningful stakeholder engagement. Scenario-planning approaches in marine social ecological systems (SES) can address some of these challenges. Using systems-thinking, scenario-planning presents the opportunity to address challenges simultaneously at different scales of interaction by addressing the needs at smaller and larger decision-making scales. We here present a prototype scenario-based approach in which we used structured decision-making tools (SDMTs) in an iterative and interactive research process with marginalised stakeholders in a small-scale fishery in South Africa’s southern Cape. Using this approach presented an opportunity for fishers to consider pathways for future responses to change while enhancing personal and local adaptive capacity. At the same time, these marginalised fishers were provided with an important opportunity to freely air their views while engaging with tools new to them. The process did not only benefit fishers, but also provided valuable insights into how they view and experience their marine SES. The use of these tools has provided a means to integrate different knowledge streams, identifying ways in which challenges presented by scale in SES is better addressed. As a next step in the prototype development, expansion to more diverse stakeholders in the biogeographical region relevant for this fishery is recommended. We highlight how this approach can contribute to multi-level governance. When considering EAF implementation, we highlight how engaging marginalised stakeholders need not mean losing the reproducible, transparent processes required for modern management. Lastly, we discuss how multi-scalar flow of information could improve the implementation of an EAF in a developing society, such as that of South Africa.
Teamwork and Leadership Under Fire at the Epicenter of the COVID-19 Epidemic in the Bronx
Authors: Tomer Yaron , Ng Gong Michelle , Keller Marla J. , Southern William , Kitsis Elizabeth A. , Kajita Grace R. , Shapiro Lauren I. , Jariwala Sunit P. , Epstein Eric J.
Published: March 2021

The first Covid-19 patient was admitted to Montefiore Medical Center (MMC) on March 10, 2020. Soon thereafter there was a rapid and exponential surge of Covid-19 admissions to MMC that could have resulted in catastrophic consequences if MMC had been overwhelmed, as happened in Europe. To adjust to this crisis our institution, under the inspiring leadership of Dr. Philip Ozuah, President and CEO of Montefiore Medicine, adopted an “all hands on deck” approach, mobilizing our entire workforce to expand our units to accommodate the growing number of patients being admitted. Given that the internal medicine (IM) and ICU units are part of the department of medicine (DOM), the DOM was at the center of this mobilization. The DOM is the largest department at MMC and mobilizing it required careful planning, seamless teamwork, and strong leadership. To achieve that goal, we applied a framework that we designate the “3C framework,” denoting Coordination, Communication, and Collaboration. In this report we describe the many initiatives the Montefiore Einstein DOM implemented during the Covid-19 pandemic using the 3C framework. These included establishing the Medicine Covid-19 Taskforce to lead our efforts, starting a daily newsletter for up-to-date communications, rapidly expanding the ICU and IM units, converting most specialty inpatient consults to eConsults, coordinating research studies, and more. The goal of this report is to serve as a guide on how the 3C framework helped us organize, mobilize, and energize the department of medicine effectively and efficiently during this unprecedented crisis.
Thermoacidophilic Alicyclobacillus Superoxide Dismutase: Good Candidate as Additives in Food and Medicine
Authors: Dong Xueqian , Wang Wei , Li Shannan , Han Hongyu , Lv Peiwen , Yang Chunyu
Published: March 2021

Thermoacidophilic Alicyclobacillus strains attract great interests as the resource of thermostable or acidic enzymes. In this study, a putative gene encoding superoxide dismutase (AaSOD) was identified in a thermoacidophilic Alicyclobacillus strain. With a 16-fold activity observed, the AaSOD activity expressing in the medium of manganese enrichment was much higher than that in the iron medium. In addition, the purified AaSOD can be reconstituted exclusively with either Fe2+ or Mn2+, with its Mn-bound protein showing 25-fold activity than that of Fe-bound form. The optimal temperature for AaSOD reaction was 35°C, and was highly stable at any certain temperature up to 80°C. Of particular interest, the enzyme is found to be very stable across a wide pH range spanning from 2.0 to 10.0, which confers its robust stability in the acidic stomach environment and implies striking potentials as food additive and for medical use.
Holstein and Jersey Steers Differ in Rumen Microbiota and Enteric Methane Emissions Even Fed the Same Total Mixed Ration
Authors: Islam Mahfuzul , Kim Seon-Ho , Ramos Sonny C. , Mamuad Lovelia L. , Son A-Rang , Yu Zhongtang , Lee Sung-Sil , Cho Yong-Il , Lee Sang-Suk
Published: March 2021

Previous studies have focused on the rumen microbiome and enteric methane (CH4) emissions in dairy cows, yet little is known about steers, especially steers of dairy breeds. In the present study, we comparatively examined the rumen microbiota, fermentation characteristics, and CH4 emissions from six non-cannulated Holstein (710.33 ± 43.02 kg) and six Jersey (559.67 ± 32.72 kg) steers. The steers were fed the same total mixed ration (TMR) for 30 days. After 25 days of adaptation to the diet, CH4 emissions were measured using GreenFeed for three consecutive days, and rumen fluid samples were collected on last day using stomach tubing before feeding (0 h) and 6 h after feeding. CH4 production (g/d/animal), CH4 yield (g/kg DMI), and CH4 intensity (g/kg BW0.75) were higher in the Jersey steers than in the Holstein steers. The lowest pH value was recorded at 6 h after feeding. The Jersey steers had lower rumen pH and a higher concentration of ammonia-nitrogen (NH3-N). The Jersey steers had a numerically higher molar proportion of acetate than the Holstein steers, but the opposite was true for that of propionate. Metataxonomic analysis of the rumen microbiota showed that the two breeds had similar species richness, Shannon, and inverse Simpson diversity indexes. Principal coordinates analysis showed that the overall rumen microbiota was different between the two breeds. Both breeds were dominated by Prevotella ruminicola, and its highest relative abundance was observed 6 h after feeding. The genera Ethanoligenens, Succinivibrio, and the species Ethanoligenens harbinense, Succinivibrio dextrinosolvens, Prevotella micans, Prevotella copri, Prevotella oris, Prevotella baroniae, and Treponema succinifaciens were more abundant in Holstein steers while the genera Capnocytophaga, Lachnoclostridium, Barnesiella, Oscillibacter, Galbibacter, and the species Capnocytophaga cynodegmi, Galbibacter mesophilus, Barnesiella intestinihominis, Prevotella shahii, and Oscillibacter ruminantium in the Jersey steers. The Jersey steers were dominated by Methanobrevibacter millerae while the Holstein steers by Methanobrevibacter olleyae. The overall results suggest that sampling hour has little influence on the rumen microbiota; however, breeds of steers can affect the assemblage of the rumen microbiota and different mitigation strategies may be needed to effectively manipulate the rumen microbiota and mitigate enteric CH4 emissions from these steers.
Design and High Expression of Non-glycosylated Lysostaphins in Pichia pastoris and Their Pharmacodynamic Study
Authors: Shen Wenluan , Yang Na , Teng Da , Hao Ya , Ma Xuanxuan , Mao Ruoyu , Wang Jianhua
Published: March 2021

Lysostaphin is an effective antimicrobial agent to Staphylococcus, especially for the methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Staphylococcus aureus (MDRSA). In this study, the seven lysostaphin derived mutants (rLys) were designed to overcome the barrier of glycosylation during expression in Pichia pastoris. Among them, 127A and 127A232Q had highest antimicrobial activity (MIC values 0.07–0.3 μM) to S. aureus than others and the commercial lysostaphins (1–15.8 times). There was no glycosylation during the expression in 5-L fermenter level, with the high yield of 1315 mg/L (127A) and 1141 mg/L (127A232Q), respectively. Meanwhile, 127A and 127A232Q effectively killed 99.9% of S. aureus at low concentration (1 × MIC) within 30 min, without the regrowth of pathogen. They also showed low toxicity, high pH and temperature stability. The results of in vivo therapeutic effect of 127A and 127A232Q against high virulent S. aureus CVCC546 showed that 127A and 127A232Q increased the survival rate of infected mice up to 100% at the dose of 10 mg/kg than the untreated group, reduced the bacterial translocation by 5-7 log CFU (over 99%) in organs compared to the untreated group and alleviated multiple-organ injuries (liver, kidney and spleen). These data indicated that the non-glycosylated lysostaphin 127A and 127A232Q may be a promising therapeutic agent against MDR staphylococcal infections.