bluuebunny/crossref_metadata_2025 huggingface dataset:
Perancangan dan Analisa Antena Yagi 12 Elemen untuk Module Lora RFM95W pada Frekuensi 915 MHz
Authors: Alviandi Fajar , Koesmarijanto Koesmarijanto , Darmono Hendro
Published: June 2021

Pada penelitian bertujuan untuk merancang antena Yagi 12 elemen agar dapat diaplikasikan pada module Lora RFM95W yang bekerja pada frekuensi 915 MHz, untuk mencari pengaruh daya penerimaan sinyal terhadap module Lora. Dalam penelitian ini pengujian implementasi antena yagi dan antena built-in dilakukan dengan keadaan line of sight dan non-line of sight. Hasil pengujian antena yagi 12 elemen diperoleh Return Loss sebesar -17.8 dBm serta nilai VSWR yaitu 1.29. Rata-rata gain yang diperoleh sebesar 5.6 dB. Dan hasil implementasi keadaan LOS untuk jarak 200 meter antena yagi memiliki nilai RSSI sebesar -98 dBm, sedangkan antena built-in lora memiliki level daya sebesar -109 dBm. Hasil pengujian kedua dalam keadaan Non-LOS (Halangan Tembok) pada jarak 25 m antena built-in memiliki nilai RSSI sebesar -95 dBm, sedangkan antena yagi 12 elemen sebesar -77 dBm. Hasil pengujian dalam keadaan Non-LOS (Halangan Pohon) pada jarak 25 m antena built-in memiliki nilai RSSI sebesar -84 dBm, sedangkan antena yagi 12 elemen sebesar -78 dBm. Sehingga pada implementasi antena yagi 12 elemen dan antena built-in dapat disimpulkan untuk data RSSI lebih baik antena yagi yang bersifat directional daripada antena built-in antena lora RFM95W yang bersifat omnidirectional.
Evaluation of Heterologous Biosynthetic Pathways for Methanol-Based 5-Aminovalerate Production by Thermophilic Bacillus methanolicus
Authors: Brito Luciana Fernandes , Irla Marta , Nærdal Ingemar , Le Simone Balzer , Delépine Baudoin , Heux Stéphanie , Brautaset Trygve
Published: June 2021

The use of methanol as carbon source for biotechnological processes has recently attracted great interest due to its relatively low price, high abundance, high purity, and the fact that it is a non-food raw material. In this study, methanol-based production of 5-aminovalerate (5AVA) was established using recombinant Bacillus methanolicus strains. 5AVA is a building block of polyamides and a candidate to become the C5 platform chemical for the production of, among others, δ-valerolactam, 5-hydroxy-valerate, glutarate, and 1,5-pentanediol. In this study, we test five different 5AVA biosynthesis pathways, whereof two directly convert L-lysine to 5AVA and three use cadaverine as an intermediate. The conversion of L-lysine to 5AVA employs lysine 2-monooxygenase (DavB) and 5-aminovaleramidase (DavA), encoded by the well-known Pseudomonas putida cluster davBA, among others, or lysine α-oxidase (RaiP) in the presence of hydrogen peroxide. Cadaverine is converted either to γ-glutamine-cadaverine by glutamine synthetase (SpuI) or to 5-aminopentanal through activity of putrescine oxidase (Puo) or putrescine transaminase (PatA). Our efforts resulted in proof-of-concept 5AVA production from methanol at 50°C, enabled by two pathways out of the five tested with the highest titer of 0.02 g l–1. To our knowledge, this is the first report of 5AVA production from methanol in methylotrophic bacteria, and the recombinant strains and knowledge generated should represent a valuable basis for further improved 5AVA production from methanol.
Global Screening of LUBAC and OTULIN Interacting Proteins by Human Proteome Microarray
Authors: Zhou Lijie , Ge Yingwei , Fu Yesheng , Wu Bo , Zhang Yong , Li Lei , Cui Chun-Ping , Wang Siying , Zhang Lingqiang
Published: June 2021

Linear ubiquitination is a reversible posttranslational modification, which plays key roles in multiple biological processes. Linear ubiquitin chain assembly complex (LUBAC) catalyzes linear ubiquitination, while the deubiquitinase OTULIN (OTU deubiquitinase with linear linkage specificity, FAM105B) exclusively cleaves the linear ubiquitin chains. However, our understanding of linear ubiquitination is restricted to a few substrates and pathways. Here we used a human proteome microarray to detect the interacting proteins of LUBAC and OTULIN by systematically screening up to 20,000 proteins. We identified many potential interacting proteins of LUBAC and OTULIN, which may function as regulators or substrates of linear ubiquitination. Interestingly, our results also hint that linear ubiquitination may have broad functions in diverse pathways. In addition, we recognized lymphocyte activation gene-3 (LAG3, CD223), a transmembrane receptor that negatively regulates lymphocyte functions as a novel substrate of linear ubiquitination in the adaptive immunity pathway. In conclusion, our results provide searchable, accessible data for the interacting proteins of LUBAC and OTULIN, which broaden our understanding of linear ubiquitination.
Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications
Authors: Salah Ahmed , Wang Hao , Li Yanqin , Ji Meng , Ou Wen-Bin , Qi Nianmin , Wu Yuehong
Published: June 2021

Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions. They have proven to potentially take up and process tumor-associated antigens (TAAs). In this regard, researchers have developed strategies such as genetically engineered or TAA-pulsed DC vaccines; these manipulated DCs have shown significant outcomes in clinical and preclinical models. Here, we review DC classification and address how DCs are skewed into an immunosuppressive phenotype in cancer patients. Additionally, we present the advancements in DCs as a platform for cancer immunotherapy, emphasizing the technologies used for in vivo targeting of endogenous DCs, ex vivo generated vaccines from peripheral blood monocytes, and induced pluripotent stem cell-derived DCs (iPSC-DCs) to boost antitumoral immunity.
Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells
Authors: Sararols Pauline , Stévant Isabelle , Neirijnck Yasmine , Rebourcet Diane , Darbey Annalucia , Curley Michael K. , Kühne Françoise , Dermitzakis Emmanouil , Smith Lee B. , Nef Serge
Published: June 2021

Leydig cells (LC) are the main testicular androgen-producing cells. In eutherian mammals, two types of LCs emerge successively during testicular development, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs). Both display significant differences in androgen production and regulation. Using bulk RNA sequencing, we compared the transcriptomes of both LC populations to characterize their specific transcriptional and functional features. Despite similar transcriptomic profiles, a quarter of the genes show significant variations in expression between FLCs and ALCs. Non-transcriptional events, such as alternative splicing was also observed, including a high rate of intron retention in FLCs compared to ALCs. The use of single-cell RNA sequencing data also allowed the identification of nine FLC-specific genes and 50 ALC-specific genes. Expression of the corticotropin-releasing hormone 1 (Crhr1) receptor and the ACTH receptor melanocortin type 2 receptor (Mc2r) specifically in FLCs suggests a dual regulation of steroidogenesis. The androstenedione synthesis by FLCs is stimulated by luteinizing hormone (LH), corticotrophin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH) whereas the testosterone synthesis by ALCs is dependent exclusively on LH. Overall, our study provides a useful database to explore LC development and functions.
Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5
Authors: Anwaier Gulinigaer , Lian Guan , Ma Gui-Zhi , Shen Wan-Li , Lee Chih-I , Lee Pei-Ling , Chang Zhan-Ying , Wang Yun-Xia , Tian Xiao-Yu , Gao Xiao-Li , Chiu Jeng-Jiann , Qi Rong
Published: June 2021

Background

Pathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms.

Methods

The anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined.

Results

PU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction.

Conclusion

PPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.
Examining Factors Associated With Farmers' Climate-Adaptive and Maladaptive Actions in the U.S. Midwest
Authors: Upadhaya Suraj , Arbuckle J. Gordon
Published: June 2021

The U.S. Midwest is a major producer of grain, meat, dairy, eggs, and other major agricultural commodities. It has also been increasingly impacted by climate change-related extreme weather over the last decade as droughts, extreme rains, floods, and, most recently, a severe derecho have damaged crops, livestock, and livelihoods. Climate and agricultural scientists and other stakeholders are concerned that without major shifts away from degrading practices toward regenerative systems, long-term sustainability will be compromised. We used cumulative logistic regression to analyze data from a 2020 survey of 1,059 Iowa farmers to examine (1) how farmers are adapting to increasingly variable and extreme weather-related to climate change and (2) whether selected factors were associated with different kinds of adaptive (e.g., increased use of cover crops) or potentially maladaptive (e.g., increased use of pesticides) actions. Our results found that many farmers have been taking adaptive and maladaptive actions. Stewardship ethics, attitudes toward adaptive action, and integration in conservation-related networks were consistent, positive predictors of increases in adaptive practices. On the other hand, faith in crop insurance as a coping strategy, farm scale, and other factors were associated with some maladaptive actions, with several positive predictors of adaptation also being positive predictors of maladaptation, use of pesticides and drainage in particular. This research contributes to the growing literature on climate risk management and adaptation in agricultural landscapes by providing empirical evidence of the factors related to farmers' adaptive and maladaptive actions.
Gender Differences in Atherosclerotic Vascular Disease: From Lipids to Clinical Outcomes
Authors: Vakhtangadze Tamar , Singh Tak Rajeeka , Singh Utkarsh , Baig Mirza S. , Bezsonov Evgeny
Published: June 2021

Cardiovascular diseases (CVDs) are one of the main reasons of death and morbidity in the world. Both women and men have high rates of cardiovascular morbidity and mortality, although gender-related differences in mortality and morbidity rates are observed in different age groups of the population. In the large cohort of cardiovascular disease, ischemic heart disease (IHD), heart failure (HF), systemic hypertension, and valvular heart disease are particularly common in the population. CVDs caused by atherosclerosis are in the first place in terms of frequency, that is why society is particularly interested in this problem. The development and course of atherosclerotic processes associated with lipid and other metabolic changes are characterized by a long latent period, the clinical manifestation is often an acute vascular catastrophe, which can lead to human disability and death. Differences associated with sex are observed in the clinical course and manifestations, which raises the suspicion that gender influences processes related to atherosclerosis. Atherosclerotic cardiovascular disease (ACD) includes two main most dangerous clinical manifestations: IHD and cerebrovascular disease (mainly ischemic stroke). Other less common clinical manifestations of atherosclerosis include aortic atherosclerosis and peripheral vascular disease. Gender-related differences were also identified concerning these diseases. The present review discusses the effects of gender and age on atherosclerotic processes, disease development, and clinical manifestations. The metabolic basis for the development of atherosclerosis appears to be related to sex hormones. Thus this issue is interesting and useful for doctors of different specialties.
Evaluation Method of Movable Shale Oil Resource: A Case Study of the Shahejie Formation in the Dongying Sag, Jiyang Depression
Authors: Xu Liang , Wang Min , Li Jinbu , Li Ming , Li Zheng , Zhu Rifang , Liu Huimin
Published: June 2021

Although China has enormous shale oil resource potential, oil recovery is limited at present, largely because its movable resource is not evaluated. In this study, an evaluation method for movable shale oil resources is proposed. The process first evaluates the total shale oil resource (Qtotal), and then two-dimensional nuclear magnetic resonance (NMR) technology is used to measure the free oil ratio (Rfree) and further define the quantitative relationship (F) between the movable ratio (Rm) in the free oil and centrifugal force. The movable oil resource is calculated by the total shale oil resource, free oil ratio, and movable oil ratio (Qm = Qtotal × Rfree × Rm). This method was applied to the Shahejie Formation of the Dongying Sag, Jiyang Depression, in Bohai Bay Basin, and the relationship between the free oil ratio (Rfree) and depth was established based on several core 2D NMR data. Based on the formation pressure, flowing bottom hole pressure, and relationship (F), the movable shale oil ratio (Rm) in the target area was determined. The results showed that the movable shale oil ratio (Rm) of the lower Es3 is approximately 18.9–20% in the depth range of 3,200–3,700 m, and the movable shale oil resource is approximately 2.52 × 108 t.
Improved Simulation of Arctic Circumpolar Land Area Snow Properties and Soil Temperatures
Authors: Royer Alain , Picard Ghislain , Vargel Céline , Langlois Alexandre , Gouttevin Isabelle , Dumont Marie
Published: June 2021

The impact of high latitude climate warming on Arctic snow cover and its insulating properties has key implications for the surface and soil energy balance. Few studies have investigated specific trends in Arctic snowpack properties because there is a lack of long-term in situ observations and current detailed snow models fail to represent the main traits of Arctic snowpacks. This results in high uncertainty in modeling snow feedbacks on ground thermal regime due to induced changes in snow insulation. To better simulate Arctic snow structure and snow thermal properties, we implemented new parameterizations of several snow physical processes—including the effect of Arctic low vegetation and wind on snowpack—in the Crocus detailed snowpack model. Significant improvements compared to standard Crocus snow simulations and ERA-Interim (ERAi) reanalysis snow outputs were observed for a large set of in-situ snow data over Siberia and North America. Arctic Crocus simulations produced improved Arctic snow density profiles over the initial Crocus version, leading to a soil surface temperature bias of −0.5 K with RMSE of 2.5 K. We performed Crocus simulations over the past 39 years (1979–2018) for circumpolar taiga (open forest) and pan-Arctic areas at a resolution of 0.5°, driven by ERAi meteorological data. Snowpack properties over that period feature significant increase in spring snow bulk density (mainly in May and June), a downward trend in snow cover duration and an upward trend in wet snow (mainly in spring and fall). The pan-Arctic maximum snow water equivalent shows a decrease of −0.33 cm dec−1. With the ERAi air temperature trend of +0.84 K dec−1 featuring Arctic winter warming, these snow property changes have led to an upward trend in soil surface temperature (Tss) at a rate of +0.41 K dec−1 in winter. We show that the implemented snowpack property changes increased the Tss trend by 36% compared to the standard simulation. Winter induced changes in Tss led to a significant increase of 16% (+4 cm dec−1) in the estimated active layer thickness (ALT) over the past 39 years. An increase in ALT could have a significant impact on permafrost evolution, Arctic erosion and hydrology.
Expanding the Boundaries of Informal Education Programs: An Investigation of the Role of Pre and Post-education Program Experiences and Dispositions on Youth STEM Learning
Authors: Falk John H. , Meier David D.
Published: June 2021

For generations educators have been supporting children and youth’s science, technology, engineering, and mathematics (STEM) learning through informal education programming. Such programming includes a wide variety of outdoor education programs, camp programs, and increasingly targeted STEM programs run afterschool, on weekends, and over the summer months. However, despite the positive impacts these programs have, few would argue that these programs could not be improved or be designed to better meet the needs of a broader and more diverse population of learners. Arguably, one major flaw in how most educators have approached the design and improvement of these programs—a flaw that permeates almost all informal STEM education efforts–is that either explicitly or implicitly, the focus of educators has been exclusively on what happens during the program itself. Superficially this seems reasonable. After all, the time children/youth are within the temporal and physical boundaries of the program, class, or museum is the time when educators have maximal control over events. However, given what is known about how people learn (National Academies of Sciences, 2018), we argue that this long-standing approach needs to be reconsidered.
Effect of Land Use History on Biodiversity of Pine Plantations
Authors: Uribe Sandra V. , García Nicolás , Estades Cristián F.
Published: June 2021

The growing replacement of native vegetation by forest plantations is considered a global threat to biodiversity. Significant variation in biotic communities among stands with similar management suggests that previous land use might have an effect on the capacity of forest plantations to harbor native species. The goal of our study was to determine the effect of land-use history on the biodiversity currently present in pine plantations in the coastal range of Central Chile. In particular, we hypothesized that plantations that directly replaced native forests should have higher diversity of plants and birds than plantations that were established in agricultural areas. We also expected that plantations of higher number of rotations should have fewer habitat-specialists and more generalists/exotics, reflecting a process of biotic homogenization. Using aerial photographs and satellite images encompassing a period of six decades, we classified 108 4-ha sampling units into native forests, and mature (17–20 year) pine plantations of first, second, and third rotation, of either forest or agricultural origin. At each site, we collected data on the abundance and richness of diurnal birds and understory plants, and analyzed their behavior in relation to the land-use history using Generalized Linear Models (GLMs). Also, we evaluated dissimilarity of communities of each pine plantation “treatment” to assess the occurrence of biotic homogenization. As predicted, pine plantations that directly replaced native forests had a higher abundance of forest specialists and less abundance of exotics and generalists than plantations of agricultural origin. In contrast, the number of rotations of pine plantations not only did not affect negatively the diversity and abundance of forest specialist species, but the models showed some signs of naturalization in the studied systems over time, such as the increase in the abundance of native herbs and a reduction in the abundance of their exotic counterparts. These results agree with the lack of evidence for a decrease in the dissimilarity of biotic communities in plantations with time, suggesting that the management of pine plantations in Central Chile is not promoting biotic homogenization, beyond the impact of the initial stages of land use change.
Integrated Multiomic Analysis Reveals the High-Fat Diet Induced Activation of the MAPK Signaling and Inflammation Associated Metabolic Cascades via Histone Modification in Adipose Tissues
Authors: Wang Zhe , Zhu Ming , Wang Meng , Gao Yihui , Zhang Cong , Liu Shangyun , Qu Shen , Liu Zhongmin , Zhang Chao
Published: June 2021

Background

The number of diet induced obese population is increasing every year, and the incidence of type 2 diabetes is also on the rise. Histone methylation and acetylation have been shown to be associated with lipogenesis and obesity by manipulating gene expression via the formation of repression or activation domains on chromosomes.

Objective

In this study, we aimed to explore gene activation or repression and related biological processes by histone modification across the whole genome on a high-fat diet (HFD) condition. We also aimed to elucidate the correlation of these genes that modulated by histone modification with energy metabolism and inflammation under both short-term and long-term HFD conditions.

Method

We performed ChIP-seq analysis of H3K9me2 and H3K9me3 in brown and white adipose tissues (WATs; subcutaneous adipose tissue) from mice fed with a standard chow diet (SCD) or HFD and a composite analysis of the histone modification of H3K9me2, H3K9me3, H3K4me1 and H3K27ac throughout the whole genome. We also employed and integrated two bulk RNA-seq and a single-nuclei RNA sequencing dataset and performed western blotting (WB) to confirm the gene expression levels in adipose tissue of the SCD and HFD groups.

Results

The ChIP-seq and transcriptome analysis of mouse adipose tissues demonstrated that a series of genes were activated by the histone modification of H3K9me2, H3K9me3, H3K4me1, and H3K27ac in response to HFD condition. These genes were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in lipogenesis, energy metabolism and inflammation. Several genes in the activated mitogen-activated protein kinase (MAPK) pathway might be related to both inflammation and energy metabolism in mice, rats and humans fed with HFD for a short or long term, as showed by bulk RNA-seq and single nuclei RNA-seq datasets. Western blot analyses further confirmed the increased expression of MET, VEGFA and the enhanced phosphorylation ratio of p44/42 MAPK upon HFD treatment.

Conclusion

This study expanded our understanding of the influence of eating behavior on obesity and could assist the identification of putative therapeutic targets for the prevention and treatment of metabolic disorders in the future.
Day 7 Embryos Change the Proteomics and Exosomal Micro-RNAs Content of Bovine Uterine Fluid: Involvement of Innate Immune Functions
Authors: Kusama Kazuya , Rashid Mohammad B. , Kowsar Rasoul , Marey Mohamed A. , Talukder Anup K. , Nagaoka Kentaro , Shimada Masayuki , Khatib Hasan , Imakawa Kazuhiko , Miyamoto Akio
Published: June 2021

This study aimed to characterize proteins and exosomal microRNAs (miRNAs) in the uterine flushings (UF) of cows associated with Day 7 (D7) pregnancy using the embryo donor cows of the embryo transfer program. Superovulated cows either were inseminated (AI cows) or remained non-inseminated (Ctrl cows). UF was collected on D7 in the presence of multiple embryos (AI cows) or without embryos (Ctrl cows) and subjected to isobaric tags for relative and absolute quantification protein analysis. A total of 336 proteins were identified, of which 260 proteins were more than 2-fold higher in AI cows than Ctrl cows. Gene ontology analysis revealed that many differentially expressed proteins were involved in “neutrophil-related” and “extracellular vesicular exosome-related” terms. In silico analysis of proteins with higher concentrations in the UF of AI identified 18 uniquely expressed proteins. Exosomes were isolated from the UF, from which RNA was subjected to miRNA-seq, identifying 37 miRNAs. Of these, three miRNAs were lower, and six miRNAs were higher in the UF of AI cows than those of Ctrl ones. The principal component analysis displayed a close association in miRNA and protein between bta-miR-29a, bta-miR-199b, SUGT1, and PPID. In addition, the receiver operating characteristic curve analysis showed that SUGT1 was the best predictor for the presence of embryos in the uterus. These findings suggest that the presence of multiple D7 embryos in the uterus can lead to significant changes in the protein composition and exosomal miRNA contents of UF, which could mediate innate immunological interactions between the pre-hatching embryo and the uterus in cows.
High-Dimensional Mediation Analysis With Confounders in Survival Models
Authors: Yu Zhangsheng , Cui Yidan , Wei Ting , Ma Yanran , Luo Chengwen
Published: June 2021

Mediation analysis is a common statistical method for investigating the mechanism of environmental exposures on health outcomes. Previous studies have extended mediation models with a single mediator to high-dimensional mediators selection. It is often assumed that there are no confounders that influence the relations among the exposure, mediator, and outcome. This is not realistic for the observational studies. To accommodate the potential confounders, we propose a concise and efficient high-dimensional mediation analysis procedure using the propensity score for adjustment. Results from simulation studies demonstrate the proposed procedure has good performance in mediator selection and effect estimation compared with methods that ignore all confounders. Of note, as the sample size increases, the performance of variable selection and mediation effect estimation is as well as the results shown in the method which include all confounders as covariates in the mediation model. By applying this procedure to a TCGA lung cancer data set, we find that lung cancer patients who had serious smoking history have increased the risk of deathviathe methylation markers cg21926276 and cg20707991 with significant hazard ratios of 1.2093 (95% CI: 1.2019–1.2167) and 1.1388 (95% CI: 1.1339–1.1438), respectively.
Targeted Therapies in Axial Psoriatic Arthritis
Authors: Floris Alberto , Congia Mattia , Chessa Elisabetta , Angioni Maria Maddalena , Piga Matteo , Cauli Alberto
Published: June 2021

Specific and high-quality evidence on the efficacy of the current targeted therapies for axial disease in psoriatic arthritis (axPsA) is still scarce. Indeed, almost all the cohorts investigated in clinical trials on PsA consisted of patients with peripheral arthritis, where a small number of them also had axial involvement. Only one randomized controlled trial was so far specifically designed to assess the efficacy of a biological disease-modifying antirheumatic drug (DMARD) in axPsA. For other biological and synthetic targeted DMARDs, the most specific evidence for treatment in axPsA is extrapolated frompost-hocanalyses based on PsA patients with concomitant peripheral and axial manifestations. Furthermore, the current trials andpost-hocanalysis on axPsA are affected by major limitations, including the lack of a widely accepted definition of axPsA and the lack of specific and validated outcome measures. Finally, poor data are available on the genetics of axPsA, although alleles differentially expressed in different patterns of axPsA might offer advantages in the prospective of personalized medicine in axPsA patients. Overall, this review suggests that there is an urgent need for more reliable evidence derived from studies specifically designed for axPsA and based on a validated definition of axPsA and on specific outcome measures.
Improving Passenger Experience and Trust in Automated Vehicles Through User-Adaptive HMIs: “The More the Better” Does Not Apply to Everyone
Authors: Hartwich Franziska , Hollander Cornelia , Johannmeyer Daniela , Krems Josef F.
Published: June 2021

Automated vehicles promise transformational benefits for future mobility systems, but only if they will be used regularly. However, due to the associated loss of control and fundamental change of in-vehicle user experience (shifting from active driver to passive passenger experience), many humans have reservations toward driving automation, which question their sufficient usage and market penetration. These reservations vary based on individual characteristics such as initial attitudes. User-adaptive in-vehicle Human-Machine Interfaces (HMIs) meeting varying user requirements may represent an important component of higher-level automated vehicles providing a pleasant and trustworthy passenger experience despite these barriers. In a driving simulator study, we evaluated the effects of two HMI versions (with permanent vs. context-adaptive information availability) on the passenger experience (perceived safety, understanding of driving behavior, driving comfort, driving enjoyment) and trust in automated vehicles of 50 first-time users with varying initial trust (lower vs. higher trust group). Additionally, we compared the user experience of both HMIs. Presenting driving-related information via HMI during driving improved all assessed aspects of passenger experience and trust. The higher trust group experienced automated driving as safest, most understandable and most comfortable with the context-adaptive HMI, while the lower trust group tended to experience the highest safety, understanding and comfort with the permanent HMI. Both HMIs received positive user experience ratings. The context-adaptive HMI received generally more positive ratings, even though this preference was more pronounced for the higher trust group. The results demonstrate the potential of increasing the system transparency of higher-level automated vehicles through HMIs to enhance users’ passenger experience and trust. They also consolidate previous findings on varying user requirements based on individual characteristics. User group-specific HMI effects on passenger experience support the relevance of user-adaptive HMI concepts addressing varying needs of different users by customizing HMI features, such as information availability. Consequently, providing full information permanently cannot be recommended as a universal standard for HMIs in automated vehicles. These insights represent next steps toward a pleasant and trustworthy passenger experience in higher-level automated vehicles for everyone, and support their market acceptance and thus the realization of their expected benefits for future mobility and society.
Role of the F-BAR Family Member PSTPIP2 in Autoinflammatory Diseases
Authors: Xu Jie-Jie , Li Hai-Di , Du Xiao-Sa , Li Juan-Juan , Meng Xiao-Ming , Huang Cheng , Li Jun
Published: June 2021

Proline-serine-threonine-phosphatase-interacting protein 2 (PSTPIP2) belongs to the Fes/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain family. It exhibits lipid-binding, membrane deformation, and F-actin binding activity, suggesting broader roles at the membrane–cytoskeleton interface. PSTPIP2 is known to participate in macrophage activation, neutrophil migration, cytokine production, and osteoclast differentiation. In recent years, it has been observed to play important roles in innate immune diseases and autoinflammatory diseases (AIDs). Current research indicates that the protein tyrosine phosphatase PTP-PEST, Src homology domain-containing inositol 5’-phosphatase 1 (SHIP1), and C‐terminal Src kinase (CSK) can bind to PSTPIP2 and inhibit the development of AIDs. However, the mechanisms underlying the function of PSTPIP2 have not been fully elucidated. This article reviews the research progress and mechanisms of PSTPIP2 in AIDs. PSTPIP2 also provides a new therapeutic target for the treatment of AIDs.
Corpora Amylacea in the Human Brain Exhibit Neoepitopes of a Carbohydrate Nature
Authors: Riba Marta , Augé Elisabet , Tena Iraida , del Valle Jaume , Molina-Porcel Laura , Ximelis Teresa , Vilaplana Jordi , Pelegrí Carme
Published: June 2021

Corpora amylacea (CA) in the human brain are polyglucosan bodies that accumulate residual substances originated from aging and both neurodegenerative and infectious processes. These structures, which act as waste containers, are released from the brain to the cerebrospinal fluid, reach the cervical lymph nodesviathe meningeal lymphatic system and may be phagocytosed by macrophages. Recent studies indicate that CA present certain neoepitopes (NEs) that can be recognized by natural antibodies of the IgM class, and although evidence of different kinds suggests that these NEs may be formed by carbohydrate structures, their precise nature is unknown. Here, we adapted standard techniques to examine this question. We observed that the preadsorption of IgMs with specific carbohydrates has inhibitory effects on the interaction between IgMs and CA, and found that the digestion of CA proteins had no effect on this interaction. These findings point to the carbohydrate nature of the NEs located in CA. Moreover, the present study indicates that,in vitro, the binding between certain natural IgMs and certain epitopes may be disrupted by certain monosaccharides. We wonder, therefore, whether these inhibitions may also occurin vivo. Further studies should now be carried out to assess the possiblein vivoeffect of glycemia on the reactivity of natural IgMs and, by extension, on natural immunity.
Case Report: Systemic Sclerosis After Covid-19 Infection
Authors: Fineschi Serena
Published: June 2021

The coronavirus disease (COVID-19) is a respiratory tract infection caused by the new virus SARS-CoV-2. The acute phase of the infection may in certain individuals be followed by another longer phase of disease (long COVID) of unknown etiology probably associated in certain cases with autoimmune activation. It has been shown that COVID-19 can trigger autoantibody production and in genetically predisposed patients may cause the onset or exacerbation of autoimmune diseases. We are reporting a case of mild COVID-19 infection complicated by autoantibody production and cutaneous and gastrointestinal symptoms and subsequently diagnosed with systemic sclerosis (SSc). A 47-year-old man with no history of any autoimmune diseases and in good health became sick together with his family on the 12th of November with mild symptoms: tiredness, fever, cough, and sore throat. Oropharyngeal swab for SARS-CoV-2 tested positive. He was isolated at home and did not require hospitalization. Three weeks later he presented with clinical manifestation compatible with suspicion of SSc. He briefly presented with skin rush, periorbital edema and conjunctivitis, vomiting, dysphagia, burning sensation in the skin, above all in the fingertips and around the mouth, puffy fingers, Raynaud’s phenomenon, pain at the fingertip of the middle finger where a depressed area was noticed without a clear ulceration. ANA showed a strongly positive nucleolar pattern. Anti-PM/Scl 75 and PM/Scl 100 resulted positive. High-resolution computed tomography (HCRT) showed early stage of interstitial lung disease (ILD). The patient was diagnosed with SSc based on the persistence of autoantibodies and the clinical and radiological pictures according to the ACR/EULAR classification (scores: puffy finger, 2; ILD, 2; Raynaud’s phenomenon, 3; SSc related antibodies, 3; total 10). There are several cases described in the medical literature of possible new onset of SLE after COVID-19 infection. This is the first case that describes a possible new onset of SSc. Conclusion: SARS-CoV-2 may trigger systemic sclerosis.
Factor VIII-Fc Activates Natural Killer Cells via Fc-Mediated Interactions With CD16
Authors: Lagassé H.A. Daniel , Hopkins Louis B. , Jankowski Wojciech , Jacquemin Marc G. , Sauna Zuben E. , Golding Basil
Published: June 2021

The most challenging complication associated with Factor VIII (FVIII) replacement therapy is the development of neutralizing anti-drug antibodies, or inhibitors, which occur in 23-35% of severe (FVIII level <1%) hemophilia A (HA) patients and are a serious hindrance to effective management of HA. Consequently, strategies that can either prevent anti-FVIII inhibitors from developing or “tolerize” individuals who develop such antibodies represent a clinically important unmet need. One intervention for patients with high-titer inhibitors is immune tolerance induction (ITI) therapy. Although ITI therapy is the only clinically proven strategy to eradicate anti-FVIII inhibitors, mechanisms of inhibitor reduction remain unknown. Factor VIII Fc-fusion (rFVIIIFc) is an enhanced half-life antihemophilic factor used in replacement therapy for HA. Fc-fusion is a successful protein bio-engineering platform technology. In addition to enhancement of plasma half-life via neonatal Fc receptor (FcRn) binding, other Fc-mediated interactions, including engagement with Fc gamma receptors (FcγR), may have immunological consequences. Several case reports and retrospective analyses suggest that rFVIIIFc offers superior outcomes with respect to ITI compared to other FVIII products. Previously we and others demonstrated rFVIIIFc interactions with activating FcγRIIIA/CD16. Here, we investigated if rFVIIIFc activates natural killer (NK) cells via CD16. We demonstrated rFVIIIFc signaling via CD16 independent of Von Willebrand Factor (VWF):FVIII complex formation. We established that rFVIIIFc potently activated NK cells in a CD16-dependent fashion resulting in IFNγ secretion and cytolytic perforin and granzyme B release. We also demonstrated an association between rFVIIIFc-mediated NK cell IFNγ secretion levels and the high-affinity (158V) CD16 genotype. Furthermore, we show that rFVIIIFc-activated CD16+ NK cells were able to lyse a B-cell clone (BO2C11) bearing an anti-FVIII B-cell receptor in an antibody-dependent cellular cytotoxicity (ADCC) assay. These in vitro findings provide an underlying molecular mechanism that may help explain clinical case reports and retrospective studies suggesting rFVIIIFc may be more effective in tolerizing HA patients with anti-FVIII inhibitors compared to FVIII not linked to Fc. Our in vitro findings suggest a potential use of Fc-fusion proteins acting via NK cells to target antigen-specific B-cells, in the management of unwanted immune responses directed against immunogenic self-antigens or therapeutic protein products.
Dendritic Cell-Mediated Regulation of Liver Ischemia-Reperfusion Injury and Liver Transplant Rejection
Authors: Nakano Ryosuke , Tran Lillian M. , Geller David A. , Macedo Camila , Metes Diana M. , Thomson Angus W.
Published: June 2021

Liver allograft recipients are more likely to develop transplantation tolerance than those that receive other types of organ graft. Experimental studies suggest that immune cells and other non-parenchymal cells in the unique liver microenvironment play critical roles in promoting liver tolerogenicity. Of these, liver interstitial dendritic cells (DCs) are heterogeneous, innate immune cells that appear to play pivotal roles in the instigation, integration and regulation of inflammatory responses after liver transplantation. Interstitial liver DCs (recruited in situ or derived from circulating precursors) have been implicated in regulation of both ischemia/reperfusion injury (IRI) and anti-donor immunity. Thus, livers transplanted from mice constitutively lacking DCs into syngeneic, wild-type recipients, display increased tissue injury, indicating a protective role of liver-resident donor DCs against transplant IRI. Also, donor DC depletion before transplant prevents mouse spontaneous liver allograft tolerance across major histocompatibility complex (MHC) barriers. On the other hand, mouse liver graft-infiltrating host DCs that acquire donor MHC antigen via “cross-dressing”, regulate anti-donor T cell reactivity in association with exhaustion of graft-infiltrating T cells and promote allograft tolerance. In an early phase clinical trial, infusion of donor-derived regulatory DCs (DCreg) before living donor liver transplantation can induce alterations in host T cell populations that may be conducive to attenuation of anti-donor immune reactivity. We discuss the role of DCs in regulation of warm and liver transplant IRI and the induction of liver allograft tolerance. We also address design of cell therapies using DCreg to reduce the immunosuppressive drug burden and promote clinical liver allograft tolerance.
Microbiomes of Healthy and Bleached Corals During a 2016 Thermal Bleaching Event in the Upper Gulf of Thailand
Authors: Kusdianto Heru , Kullapanich Chitrasak , Palasuk Matanee , Jandang Suppakarn , Pattaragulwanit Kobchai , Ouazzani Jamal , Chavanich Suchana , Viyakarn Voranop , Somboonna Naraporn
Published: June 2021

Global warming has caused elevated seawater temperature and coral bleaching, including events on shallow reefs in the upper Gulf of Thailand (uGoT). Previous studies have reported an association between loss of zooxanthellae and coral bleaching. However, studies on the microbial diversity of prokaryotes and eukaryotes (microbiome) as coral holobionts are also important and this information is still limited in the uGoT. To address this shortcoming, this report provided baseline information on the prokaryotic (bacteria and archaea) and eukaryotic microbes of healthy and bleached colonies of four prevalent corals Acropora humilis, Acropora millepora, Platygyra sinensis, and Porites lutea and surrounding seawater and sediments, using 16S and 18S rRNA gene next-generation sequencing. Both prokaryotic and eukaryotic microbes showed isolated community profiles among sample types (corals, sediment, and seawater) (ANOSIM: P < 0.001, R = 0.51 for prokaryotic profiles and P < 0.001, R = 0.985 for eukaryotic microbe profiles). Among coral species, P. sinensis showed the most diverse prokaryotic community compared with the others (ANOSIM: P < 0.001, R = 0.636), and P. lutea showed the most diverse eukaryotic microbes (P = 0.014, R = 0.346). Healthy and bleached corals had some different microbiomes in species and their prevalences. For instance, the significant increase of Alphaproteobacteria in P. sinensis resulted in reduced prokaryotic community evenness and altered potential metabolic profiles (i.e., increased amino acid metabolism and genetic information processing and transcription, but decreased prokaryotic functions in cell motility, signaling, and transduction). For eukaryotic microbes, the loss of the algal Symbiodinium (colloquially known as zooxanthellae) in bleached corals such as P. lutea resulted in increased Chromista and Protista and, hence, clearly distinct eukaryotic microbe (including fungi) communities in healthy vs. bleached colonies of corals. Bleached corals were enriched in bacterial pathogens (e.g., Acinetobacter, Helicobacter, Malassesia, and Aspergillus) and decreased coral-beneficial prokaryotic and eukaryotic microbes (e.g., Rhizobiales and Symbiodinium). Additionally, this study identified microbiome species in bleached P. lutea that might help bleaching recovery (e.g., high abundance of Rhizobiales, Oceanospirillales, Flavobacteriales, and Alteromonadales). Overall, our coral-associated microbiome analyses identified altered diversity patterns of bacteria, archaea, fungi, and eukaryotic microbes between healthy and bleached coral species that are prevalent in the uGoT. This knowledge supports our ongoing efforts to manipulate microbial diversity as a means of reducing the negative impacts of thermal bleaching events in corals inhabiting the uGoT.
Distribution Pattern of the Benthic Meiofaunal Community Along the Depth Gradient of the Western Indian Continental Margin, Including the OMZ and Abyssal Plain
Authors: Sautya Sabyasachi , Gaikwad Santosh , Khokher Sanofar , Pradhan Umesh Kumar , Chatterjee Soumya , Choudhury Amita , Sahu Balaram , Attri Suman
Published: June 2021

The continental margin harbors a variety of habitats that support incredible biodiversity and the function of their oceans' ecosystems. The meiofauna is considered a significant component of the benthic faunal community from the polar to the tropical regions. The meiofaunal community in the deep Indian Ocean, especially along the depth gradient, is poorly investigated. The present study aims to explore the benthic meiofaunal community structure along the depth gradients and its associated environment in the western Indian continental margin (WICM) and abyssal plain in the eastern Arabian Sea. Sediment samples were collected from seven different depths (111–3,918 m) along the WICM including the oxygen minimum zone (OMZ) and abyssal plain. A total of 22 taxa (groups) were encountered along the WICM. The nematodes (85%) were the most dominant taxa in all the depths, followed by copepods (11%), nauplii (5%), and polychaetes (1.36%). Our results suggest that (a) the organic matter has accumulated in OMZ sites; (b) a high amount of total organic carbon did not influence the meiofaunal density or biomass; (c) oxygen and depth gradients were significant drivers of the meiofaunal community, low levels of oxygen contributed to lower taxa diversity and density at 485 and 724 m depths; (d) a significant relationship of meiofaunal density and biomass with chloroplastic pigment equivalent (CPE) values indicates pelagic-benthic coupling. Copepods, nauplii, tanaidaceans, isopods, kinorhynchs, and cumaceans were affected by the low-oxygen conditions at the OMZ sites. Enhanced meiofaunal diversity, density, and biomass at deeper sites (non-OMZ-D) was attributed to increased abundance of copepods, nauplii, tanaidaceans, isopods, kinorhynchs, and cumaceans and were mostly concentrated on the surface sediment (0–4 cm) triggered by enhanced bottom-water oxygen and freshness of available food outside the OMZ except 3,918 m. Therefore, the present study showed the meiofaunal community pattern with respect to depth gradients and their related environmental changes, including the OMZ along the WICM and abyssal plain in the Arabian Sea. Based on this study, the future extent of these underestimated marine ecosystems must be considered a priority to understand its functional consequences.