bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Flow in Phaseolus Beans and Its Role as a Plausible Driver of Ecological Fitness and Expansion of Cultigens
Authors: Chacón-Sánchez María Isabel , Martínez-Castillo Jaime , Duitama Jorge , Debouck Daniel G.
Published: May 2021

The genusPhaseolus, native to the Americas, is composed of more than eighty wild species, five of which were domesticated in pre-Columbian times. Since the beginning of domestication events in this genus, ample opportunities for gene flow with wild relatives have existed. The present work reviews the extent of gene flow in the genusPhaseolusin primary and secondary areas of domestication with the aim of illustrating how this evolutionary force may have conditioned ecological fitness and the widespread adoption of cultigens. We focus on the biological bases of gene flow in the genusPhaseolusfrom a spatial and time perspective, the dynamics of wild-weedy-crop complexes in the common bean and the Lima bean, the two most important domesticated species of the genus, and the usefulness of genomic tools to detect inter and intraspecific introgression events. In this review we discuss the reproductive strategies of severalPhaseolusspecies, the factors that may favor outcrossing rates and evidence suggesting that interspecific gene flow may increase ecological fitness of wild populations. We also show that wild-weedy-crop complexes generate genetic diversity over which farmers are able to select and expand their cultigens outside primary areas of domestication. Ultimately, we argue that more studies are needed on the reproductive biology of the genusPhaseolussince for most species breeding systems are largely unknown. We also argue that there is an urgent need to preserve wild-weedy-crop complexes and characterize the genetic diversity generated by them, in particular the genome-wide effects of introgressions and their value for breeding programs. Recent technological advances in genomics, coupled with agronomic characterizations, may make a large contribution.
Higher, Faster, Better: Maternal Effects Shorten Time Lags and Increase Morphological Defenses in Daphnia lumholtzi Offspring Generations
Authors: Graeve Annette , Janßen Marjan , Villalba de la Pena Mariana , Tollrian Ralph , Weiss Linda C.
Published: May 2021

Prey species can respond to the presence of predators by inducing phenotypic plastic traits which form morphological, life history or behavioral defenses. These so-called inducible defenses have evolved within a cost-benefit framework. They are only formed when they are needed, and costs associated with defenses are saved when predators are not present. However, a disadvantage compared to permanent defenses are lag phases between predator perception and the full formation of defenses. This may be especially important when the predation risk persists for longer periods, e.g., outlasts one generation and challenges prey offspring. We hypothesized that transgenerational induced phenotypic plasticity reduces lag phases in situations where hazards threaten specimens over several generations. We tested this in three generations of the freshwater crustaceanDaphnia lumholtziusing the three-spined sticklebackGasterosteus aculeatusas predator. In the presence of chemical cues from fishD. lumholtziexpresses elongated head and tail spines. In the F0 generation defenses are constraint by a comparatively long lag phase and are not developed prior to the 3rd instar. In the F1, and F2 of induced animals this lag phase is shortened and defenses are developed upon birth. We show that induction of TGP in the mothers takes place already during the juvenile stages and transfers to the offspring generation in forms of shortened time lags and enhanced trait expression. When progeny is additionally exposed to fish cues as embryos, the addition of maternal and embryonic effects further enhances the magnitude of defense expression. Our findings detail a distinguished strategy of transgenerational phenotypic plasticity which allows to shorten lag phases of trait changes in phenotypic plasticity.
Reproductive Mode and Conflict Shape the Evolution of Male Attributes and Rate of Speciation in the Fish Family Poeciliidae
Authors: Reznick David N. , Travis Joseph , Pollux Bart J. A. , Furness Andrew I.
Published: May 2021

Sexual conflict is caused by differences between the sexes in how fitness is maximized. These differences are shaped by the discrepancy in the investment in gametes, how mates are chosen and how embryos and young are provided for. Fish in the family Poeciliidae vary from completely provisioning eggs before they are fertilized to providing virtually all resources after fertilization via the functional equivalent of a mammalian placenta. This shift in when females provision their young relative to when an egg is fertilized is predicted to cause a fundamental change in when and how sexual conflict is manifested. If eggs are provisioned before fertilization, there should be strong selection for females to choose with whom they mate. Maternal provisioning after fertilization should promote a shift to post-copulatory mate choice. The evolution of maternal provisioning may in turn have cascading effects on the evolution of diverse features of the biology of these fish because of this shift in when mates are chosen. Here we summarize what these consequences are and show that the evolution of maternal provisioning is indeed associated with and appears to govern the evolution of male traits associated with sexual selection. The evolution of placentas and associated conflict does not cause accelerated speciation, contrary to predictions. Accelerated speciation rate is instead correlated with the evolution of male traits associated with sexual selection, which implies a more prominent role of pre-copulatory reproductive isolation in causing speciation in this family.
Linking Ecosystem Services to Social Well-Being: An Approach to Assess Land Degradation
Authors: Sharafatmandrad Mohsen , Khosravi Mashizi Azam
Published: May 2021

Land degradation usually leads to the loss of ecosystem services, which may threaten social well-being. There is no approach to identify and manage all ecosystem services based on their importance in degradation processes and social systems. This study aimed to link ecosystem services to social well-being in order to assess rangeland degradation. Eleven ecosystem services (forage production, water yield, edible plants, fuel, medicinal plants, pollination, gas regulation, soil resistivity to erosion, soil fertility, scenic beauty, and recreation) were assessed in a semiarid rangeland near Bardsir city, Kerman Province, southeast Iran. There were significant differences between the rangeland types in providing ecosystem services (p < 0.05). Four criteria and 17 indices of social well-being were weighed according to their importance for local stakeholders. Rangeland degradation was estimated using the weight of the indices for social well-being and ecosystem services. Discriminant analysis indicated that supporting services (soil fertility) and provisioning services (water yield and forage production) had the greatest impact on rangeland degradation, which is related to food security in social well-being. Ecosystem services and social well-being declined in medium and severe degradation due to plant composition change and overgrazing based on principal component analysis (PCA). More than 70% of the watershed has been highly and severely degraded. There was a trade-off relationship between ecosystem services and social well-being in very severe degraded areas because of social well-being promotion due to agriculture expansion. Based on our approach, the loss rate of the ecosystem services and social well-being indices in each degradation category is a good guide for management programs and decision-makers to meet both the needs of the people and the preservation of ecosystems.
Self-Organization and Information Processing: From Basic Enzymatic Activities to Complex Adaptive Cellular Behavior
Authors: De la Fuente Ildefonso M. , Martínez Luis , Carrasco-Pujante Jose , Fedetz Maria , López José I. , Malaina Iker
Published: May 2021

One of the main aims of current biology is to understand the origin of the molecular organization that underlies the complex dynamic architecture of cellular life. Here, we present an overview of the main sources of biomolecular order and complexity spanning from the most elementary levels of molecular activity to the emergence of cellular systemic behaviors. First, we have addressed the dissipative self-organization, the principal source of molecular order in the cell. Intensive studies over the last four decades have demonstrated that self-organization is central to understand enzyme activity under cellular conditions, functional coordination between enzymatic reactions, the emergence of dissipative metabolic networks (DMN), and molecular rhythms. The second fundamental source of order is molecular information processing. Studies on effective connectivity based on transfer entropy (TE) have made possible the quantification in bits of biomolecular information flows in DMN. This information processing enables efficient self-regulatory control of metabolism. As a consequence of both main sources of order, systemic functional structures emerge in the cell; in fact, quantitative analyses with DMN have revealed that the basic units of life display a global enzymatic structure that seems to be an essential characteristic of the systemic functional metabolism. This global metabolic structure has been verified experimentally in both prokaryotic and eukaryotic cells. Here, we also discuss how the study of systemic DMN, using Artificial Intelligence and advanced tools of Statistic Mechanics, has shown the emergence of Hopfield-like dynamics characterized by exhibiting associative memory. We have recently confirmed this thesis by testing associative conditioning behavior in individual amoeba cells. In these Pavlovian-like experiments, several hundreds of cells could learn new systemic migratory behaviors and remember them over long periods relative to their cell cycle, forgetting them later. Such associative process seems to correspond to an epigenetic memory. The cellular capacity of learning new adaptive systemic behaviors represents a fundamental evolutionary mechanism for cell adaptation.
Goat AKAP12: Indel Mutation Detection, Association Analysis With Litter Size and Alternative Splicing Variant Expression
Authors: Kang Zihong , Bai Yangyang , Lan Xianyong , Zhao Haiyu
Published: May 2021

A-kinase anchoring protein 12 (AKAP12) plays key roles in male germ cells and female ovarian granulosa cells, whereas its influence on livestock litter size remains unclear. Herein we detected the genetic variants of AKAP12 gene and their effects on litter size as well as alternative splicing variants expression in Shaanbei white cashmere (SBWC) goats, aiming at exploring theoretical basis for goat molecular breeding. We identified two Insertion/deletions (Indels) (7- and 13-bp) within the AKAP12 gene. Statistical analyses demonstrated that the 13-bp indel mutation in the 3′ UTR was significantly associated with litter size (n = 1,019), and the carriers with DD genotypes presented lower litter sizes compared with other carriers (P < 0.01). Bioinformatics analysis predicted that this 13-bp deletion sequence could bind to the seed region of miR-181, which has been documented to suppress porcine reproductive and respiratory syndrome virus (PRRSV) infection by targeting PRRSV receptor CD163 and affect the pig litter size. Therefore, luciferase assay for this 13-bp indel binding with miRNA-181 was performed, and the luciferase activity of pcDNA-miR-181-13bp-Deletion-allele vector was significantly lower than that of the pcDNA-miR-181-13bp-Insertion-allele vector (P < 0.05), suggesting the reduced binding capability with miR-181 in DD genotype. Given that alternative spliced variants and their expression considerably account for the Indel genetic effects on phenotypic traits, we therefore detected the expression of the alternative spliced variants in different tissues and identified that AKAP12-AS2 exhibited the highest expression levels in testis tissues. Interestingly, the AKAP12-AS2 expression levels of homozygote DD carriers were significantly lower than that of individuals with heterozygote ID, in both testis and ovarian tissues (P < 0.05), which is consistent with the effect of the 13-bp deletion on the reduced litter size. Taken together, our results here suggest that this 13-bp indel mutation within goat AKAP12 might be utilized as a novel molecular marker for improving litter size in goat breeding.
Exhausting circ_0136474 and Restoring miR-766-3p Attenuate Chondrocyte Oxidative Injury in IL-1β-Induced Osteoarthritis Progression Through Regulating DNMT3A
Authors: Zhu Haiquan , Zhu Shaobo , Shang Xiuchao , Meng Xiangsheng , Jing Sheng , Yu Li , Deng Yu
Published: May 2021

Circular RNA circ_0136474 is a new contributor of human osteoarthritis (OA) by suppressing chondrocyte proliferation. However, its role and mechanism in OA chondrocyte injury remain ill defined. Herein, we performed real-time quantitative PCR to detect RNA expression of circ_0136474, microRNA (miR)-766-3p, and DNA methyltransferase 3A (DNMT3A) and utilized Western blotting to measure protein expression of DNMT3A, matrix metalloproteinase-1 (MMP1), MMP13, collagen II, proliferating cell nuclear antigen (PCNA) and B cell lymphoma (Bcl)-2, and Bcl-2-associated X protein (Bax). Direct interaction between miR-766-3p and circ_0136474 or DNMT3A was confirmed by bioinformatics algorithms, dual-luciferase reporter assay, and RNA immunoprecipitation. Functional experiments including cell counting kit-8 assay, flow cytometry, and special assay kits were employed to measure oxidative injury in interleukin (IL)-1β-induced OA-like chondrocytes. First, IL-1β administration induced cell viability inhibition, collagen II suppression, and promotion of MMP1 and MMP13 in human chondrocyte CHON-001 cells. Expression of circ_0136474 and DNMT3A was upregulated, and miR-766-3p was downregulated in human OA cartilages and IL-1β-induced CHON-001 cells. Functionally, both blocking circ_0136474 and upregulating miR-766-3p could rescue cell viability and levels of PCNA, Bcl-2, reduced glutathione (GSH), and total superoxide dismutase (SOD), and attenuate apoptosis rate and levels of Bax, reactive oxygen species (ROS), and lipid peroxidation malondialdehyde (MDA). Mechanically, circ_0136474 served as miR-766-3p sponge to govern miR-766-3p-targeted DNMT3A expression. Accidently, restoring DNMT3A counteracted the miR-766-3p upregulation role, and silencing miR-766-3p weakened circ_0136474 knockdown effect in IL-1β-induced CHON-001 cells. In conclusion, exhausting circ_0136474 could mitigate OA chondrocyte oxidative injury through regulating miR-766-3p/DNMT3A axis.
A Sight on Single-Cell Transcriptomics in Plants Through the Prism of Cell-Based Computational Modeling Approaches: Benefits and Challenges for Data Analysis
Authors: Bobrovskikh Aleksandr , Doroshkov Alexey , Mazzoleni Stefano , Cartenì Fabrizio , Giannino Francesco , Zubairova Ulyana
Published: May 2021

Single-cell technology is a relatively new and promising way to obtain high-resolution transcriptomic data mostly used for animals during the last decade. However, several scientific groups developed and applied the protocols for some plant tissues. Together with deeply-developed cell-resolution imaging techniques, this achievement opens up new horizons for studying the complex mechanisms of plant tissue architecture formation. While the opportunities for integrating data from transcriptomic to morphogenetic levels in a unified system still present several difficulties, plant tissues have some additional peculiarities. One of the plants’ features is that cell-to-cell communication topology through plasmodesmata forms during tissue growth and morphogenesis and results in mutual regulation of expression between neighboring cells affecting internal processes and cell domain development. Undoubtedly, we must take this fact into account when analyzing single-cell transcriptomic data. Cell-based computational modeling approaches successfully used in plant morphogenesis studies promise to be an efficient way to summarize such novel multiscale data. The inverse problem’s solutions for these models computed on the real tissue templates can shed light on the restoration of individual cells’ spatial localization in the initial plant organ—one of the most ambiguous and challenging stages in single-cell transcriptomic data analysis. This review summarizes new opportunities for advanced plant morphogenesis models, which become possible thanks to single-cell transcriptome data. Besides, we show the prospects of microscopy and cell-resolution imaging techniques to solve several spatial problems in single-cell transcriptomic data analysis and enhance the hybrid modeling framework opportunities.
Insights Into Host Cell Cytokines in Chlamydia Infection
Authors: Xiang Wenjing , Yu Nanyan , Lei Aihua , Li Xiaofang , Tan Shui , Huang Lijun , Zhou Zhou
Published: May 2021

Chlamydial infection causes a number of clinically relevant diseases and induces significant morbidity in humans. Immune and inflammatory responses contribute to both the clearance ofChlamydiainfection and pathology in host tissues.Chlamydiainfection stimulates host cells to produce a large number of cytokines that trigger and regulate host immune responses againstChlamydia. However, inappropriate responses can occur with excessive production of cytokines, resulting in overreactive inflammatory responses and alterations in host orChlamydiametabolism. As a result,Chlamydiapersists and causes wound healing delays, leading to more severe tissue damage and triggering long-lasting fibrotic sequelae. Here, we summarize the roles of cytokines inChlamydiainfection and pathogenesis, thus advancing our understanding chlamydial infection biology and the pathogenic mechanisms involved.
Functional Recovery in Autoimmune Encephalitis: A Prospective Observational Study
Authors: Seifert-Held Thomas , Eberhard Katharina , Lechner Christian , Macher Stefan , Hegen Harald , Moser Tobias , Jacob Gregor Brecl , Puttinger Gertraud , Topakian Raffi , Guger Michael , Kacar Emrah , Zoche Lea , De Simoni Desiree , Seiser Andreas , Oberndorfer Stefan , Baumgartner Christoph , Struhal Walter , Zimprich Friedrich , Sellner Johann , Deisenhammer Florian , Enzinger Christian , Reindl Markus , Rauschka Helmut , Berger Thomas , Höftberger Romana
Published: May 2021

Background

Prospective observations of functional recovery are lacking in patients with autoimmune encephalitis defined by antibodies against synaptic proteins and neuronal cell surface receptors.

Methods

Adult patients with a diagnosis of autoimmune encephalitis were included into a prospective registry. At 3, 6 and 12 months of follow-up, the patients’ modified Rankin Scale (mRS) was obtained.

Results

Patients were stratified into three groups according to their antibody (Ab) status: anti-NMDAR-Ab (n=12; group I), anti-LGI1/CASPR2-Ab (n=35; group II), and other antibodies (n=24; group III). A comparably higher proportion of patients in group I received plasma exchange/immunoadsorption and second line immunosuppressive treatments at baseline. A higher proportion of patients in group II presented with seizures. Group III mainly included patients with anti-GABABR-, anti-GAD65- and anti-GlyR-Ab. At baseline, one third of them had cancer. Patients in groups I and III had much higher median mRS scores at 3 months compared to patients in group II. A median mRS of 1 was found at all follow-up time points in group II.

Conclusions

The different dynamics in the recovery of patients with certain autoimmune encephalitides have important implications for clinical trials. The high proportion of patients with significant disability at 3 months after diagnosis in groups I and III points to the need for improving treatment options. More distinct scores rather than the mRS are necessary to differentiate potential neurological improvements in patients with anti-LGI1-/CASPR2-encephalitis.
Remdesivir Alleviates Acute Kidney Injury by Inhibiting the Activation of NLRP3 Inflammasome
Authors: Yin Liang , Zhao Haoxin , Zhang Huiyu , Li Yi , Dong Yuhao , Ju Huijin , Kong Feng , Zhao Shengtian
Published: May 2021

Acute kidney injury (AKI) is a frequent clinical complication in critically ill patients, and it rapidly develops into renal failure with high morbidity and mortality. However, other than dialysis, no effective therapeutic interventions can offer reliable treatment to limit renal injury and improve survival. Here, we firstly reported that remdesivir (RDV, GS-5734), a broad-spectrum antiviral nucleotide prodrug, alleviated AKI by specifically inhibiting NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages. Mechanically, RDV effectively suppressed the activities of nuclear transcription factor (NF)-κB, mitogen-activated protein kinase (MAPK), which further led to the reduction of the inflammasome genes of NLRP3 transcription, limiting the activation of NLRP3 inflammasome in vivo and in vitro. RDV also inhibited other pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-12, IL-1β, and interferon–β (IFN-β), leading to the reduction of inflammatory factors release. Thus, RDV can ameliorate AKI via modulating macrophage inflammasome activation and inflammatory immune responses and may have a therapeutic potential for patients with AKI in clinical application.
Fusobacterium nucleatum Facilitates M2 Macrophage Polarization and Colorectal Carcinoma Progression by Activating TLR4/NF-κB/S100A9 Cascade
Authors: Hu Lijun , Liu Yan , Kong Xuehua , Wu Rui , Peng Qi , Zhang Yan , Zhou Lan , Duan Liang
Published: May 2021

Fusobacterium nucleatum (Fn) has been considered as a significant contributor in promoting colorectal carcinoma (CRC) development by suppressing host anti-tumor immunity. Recent studies demonstrated that the aggregation of M2 macrophage (Mφ) was involved in CRC progress driven by Fn infection. However, the underlying molecular mechanisms are poorly characterized. Here, we investigated the role of Fn in Mφ polarization as well as its effect on CRC malignancy. Fn infection facilitated differentiation of Mφ into the M2-like Mφ phenotype by in vitro study. Histological observation from Fn-positive CRC tissues confirmed the abundance of tumor-infiltrating M2-like Mφ. Fn-induced M2-like Mφ polarization was weakened once inhibiting a highly expressed damage-associated molecular pattern (DAMP) molecule S100A9 mainly derived from Fn-challenged Mφ and CRC cells. In addition, Fn-challenged M2-like Mφ conferred CRC cells a more malignant phenotype, showing stronger proliferation and migration characteristics in vitro and significantly enhanced tumor growth in vivo, all of which were partially inhibited when S100A9 was lost. Mechanistic studies further demonstrated that activation of TLR4/NF-κB signaling pathway mediated Fn-induced S100A9 expression and subsequent M2-like Mφ activation. Collectively, these findings indicate that elevated S100A9 in Fn-infected CRC microenvironment participates in M2-like Mφ polarization, thereby facilitating CRC malignancy. Furthermore, targeting TLR4/NF-κB/S100A9 cascade may serve as promising immunotherapeutic strategy for Fn-associated CRC.
In Patients With Obesity, the Number of Adipose Tissue Mast Cells Is Significantly Lower in Subjects With Type 2 Diabetes
Authors: Lopez-Perez David , Redruello-Romero Anaïs , Garcia-Rubio Jesús , Arana Carlos , Garcia-Escudero Luis A. , Tamayo Francisco , Puentes-Pardo Jose D. , Moreno-SanJuan Sara , Salmeron Javier , Blanco Armando , Galvez Julio , Leon Josefa , Carazo Ángel
Published: May 2021

Type 2 diabetes (T2D) is a rising global health problem mainly caused by obesity and a sedentary lifestyle. In healthy individuals, white adipose tissue (WAT) has a relevant homeostatic role in glucose metabolism, energy storage, and endocrine signaling. Mast cells contribute to these functions promoting WAT angiogenesis and adipogenesis. In patients with T2D, inflammation dramatically impacts WAT functioning, which results in the recruitment of several leukocytes, including monocytes, that enhance this inflammation. Accordingly, the macrophages population rises as the WAT inflammation increases during the T2D status worsening. Since mast cell progenitors cannot arrive at WAT, the amount of WAT mast cells depends on how the new microenvironment affects progenitor and differentiated mast cells. Here, we employed a flow cytometry-based approach to analyze the number of mast cells from omental white adipose tissue (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 100 patients with obesity. Additionally, we measured the number of mast cell progenitors in a subcohort of 15 patients. The cohort was divided in three groups: non-T2D, pre-T2D, and T2D. Importantly, patients with T2D have a mild condition (HbA1c <7%). The number of mast cells and mast cell progenitors was lower in patients with T2D in both o-WAT and s-WAT in comparison to subjects from the pre-T2D and non-T2D groups. In the case of mast cells in o-WAT, there were statistically significant differences between non-T2D and T2D groups (p = 0.0031), together with pre-T2D and T2D groups (p=0.0097). However, in s-WAT, the differences are only between non-T2D and T2D groups (p=0.047). These differences have been obtained with patients with a mild T2D condition. Therefore, little changes in T2D status have a huge impact on the number of mast cells in WAT, especially in o-WAT. Due to the importance of mast cells in WAT physiology, their decrease can reduce the capacity of WAT, especially o-WAT, to store lipids and cause hypoxic cell deaths that will trigger inflammation.
COVID-19 mRNA Vaccines Are Generally Safe in the Short Term: A Vaccine Vigilance Real-World Study Says
Authors: Chen Gang , Li Xiaolin , Sun Meixing , Zhou Yangzhong , Yin Meifang , Zhao Bin , Li Xuemei
Published: May 2021

Background

The prophylactic vaccination of COVID-19 mRNA vaccines is the first large-scale application of this kind in the human world. Over 1.8 million doses of the COVID-19 vaccine had been administered in the US until December 2020, and around 0.2% submitted AE reports to the Vaccine Adverse Event Reporting System (VAERS). This study aimed to evaluate the AEs following immunization (AEFIs) and analyze the potential associations based on the information from the VAERS database.

Methods

We searched the VAERS database recorded AEFIs after COVID-19 vaccines in December 2020. After data mapping, we summarized demographic and clinical features of reported cases. Fisher exact test was used to comparing the clinical characteristics among AE groups with an anaphylactic response, concerning neurological disorders and death.

Results

VAERS reported 3,908 AEFIs of COVID-19 vaccines in December 2020. Most (79.68%) were reported after the first dose of the vaccine. Among the reported cases, we found that general disorders (48.80%), nervous system disorders (46.39%), and gastrointestinal disorders (25.54%) were the most common AEFIs. The allergy history was more frequent in vaccine recipients with anaphylactic reactions than those without (64.91% vs. 49.62%, OR = 1.88, P <0.017). History of anxiety or depression was more common in subjects reporting severe neurological AEFIs than those reporting other AEFIs (18.37% vs. 7.85%, OR = 2.64, P <0.017). Cases reporting death were significantly older (79.36 ± 10.41-year-old vs. 42.64 ± 12.55-year-old, P <0.01, 95% CI 29.30–44.15) and more likely experienced hypertension (50.00% vs. 11.42%, OR = 7.76, P <0.01) and neurological disorders (50.00% vs. 5.36%, OR = 17.65, P <0.01) than other vaccine recipients. The outpatient and emergency room visit rates were 11.92 and 22.42% for AEFIs, and 2.53% of cases needed hospitalization.

Conclusion

AEFIs of COVID-19 mRNA vaccines were generally non-severe local or systemic reactions. A prior allergy history is the risk factor for anaphylaxis, while a history of anxiety may link with severe neurological AEs. Such vaccine recipients need further evaluation and monitor.
Identification of Inflammation-Related Biomarker Lp-PLA2 for Patients With COPD by Comprehensive Analysis
Authors: Deng Mingming , Yin Yan , Zhang Qin , Zhou Xiaoming , Hou Gang
Published: May 2021

Purpose

Chronic obstructive pulmonary disease (COPD) is a complex and persistent lung disease and lack of biomarkers. The aim of this study is to screen and verify effective biomarkers for medical practice.

Methods

Differential expressed genes analysis and weighted co-expression network analysis were used to explore potential biomarker. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene set enrichment analysis (GSEA) analysis were used to explore potential mechanism. CIBERSORTx website was used to evaluate tissue-infiltrating immune cells. Enzyme-linked immunosorbent assay (ELISA) was used to assess the concentrations of the Lp-PLA2 in serum.

Results

Ten genes were selectedviacombined DEGs and WGCNA. Furthermore, PLA2G7 was choose based on validation from independent datasets. Immune infiltrate and enrichment analysis suggest PLA2G7 may regulate immune pathwayviamacrophages. Next, Lp-PLA2(coded by PLA2G7 gene) level was upregulated in COPD patients, increased along with The Global Average of COPD (GOLD) stage. In additional, Lp-PLA2 level was significant correlate with FEV1/FVC, BMI, FFMI, CAT score, mMRC score and 6MWD of COPD patients. Finally, the predictive efficiency of Lp-PLA2 level (AUC:0.796) and derived nomogram model (AUC:0.884) in exercise tolerance was notably superior to that of the sit-to-stand test and traditional clinical features.

Conclusion

Lp-PLA2 is a promising biomarker for COPD patients and is suitable for assessing exercise tolerance in clinical practice.
Human Microglia Extensively Reconstitute in Humanized-BLT Mice With Human Interleukin-34 Transgene and Support HIV-1 Brain Infection
Authors: Zhang Jianshui , Lohani Saroj Chandra , Cheng Yilun , Wang Tao , Guo Lili , Kim Woong-Ki , Gorantla Santhi , Li Qingsheng
Published: May 2021

Humanized bone marrow-liver-thymic (hu-BLT) mice develop a functional immune system in periphery, nevertheless, have a limited reconstitution of human myeloid cells, especially microglia, in CNS. Further, whether bone marrow derived hematopoietic stem and progenitor cells (HSPCs) can enter the brain and differentiate into microglia in adults remains controversial. To close these gaps, in this study we unambiguously demonstrated that human microglia in CNS were extensively reconstituted in adult NOG mice with human interleukin-34 transgene (hIL34 Tg) from circulating CD34+ HSPCs, nonetheless not in hu-BLT NOG mice, providing strong evidence that human CD34+ HSPCs can enter adult brain and differentiate into microglia in CNS in the presence of hIL34. Further, the human microglia in the CNS of hu-BLT-hIL34 NOG mice robustly supported HIV-1 infection reenforcing the notion that microglia are the most important target cells of HIV-1 in CNS and demonstrating its great potential as an in vivo model for studying HIV-1 pathogenesis and evaluating curative therapeutics in both periphery and CNS compartments.
Monofloral Triadica Cochinchinensis Honey Polyphenols Improve Alcohol-Induced Liver Disease by Regulating the Gut Microbiota of Mice
Authors: Luo Liping , Zhang Jinping , Liu Mingyan , Qiu Shengrong , Yi Shengxiang , Yu Wenjie , Liu Tao , Huang Xueyong , Ning Fangjian
Published: May 2021

Honey produced from medicinal plants holds great promise for human health. Increasing evidence suggests that the gut microbiota plays an important role in liver pathology after alcohol intake. The aim of this study was to identify the polyphenol composition of triadica cochinchinensis honey (TCH), and to study the potential effect of honey polyphenols on the regulation of gut microbes in mice with alcohol-induced liver injury and the improvement of alcohol-induced liver disease. For these purposes, a total of 190 compounds were identified and 27 of them were quantified by ultraperformance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and we successfully established a mouse model of alcohol-induced liver injury. The results show that TCH polyphenols can significantly restore the levels of ALT and AST, and TCH intervention can significantly improve the pathological changes of liver tissue in alcohol-exposed mice. Additionally, a significant decrease was observed in Firmicutes/Bacteroidetes after TCH treatment. Moreover, KEGG pathways of ATP-binding cassette (ABC) transporters, two-component system and biosynthesis of amino acids enriched the most differentially expressed genes after TCH intervention for 8 weeks. Our results may have important implications for the use of TCH as a functional food component with potential therapeutic utility against alcohol-induced liver disease.
Credit Systems for Bycatch and Biodiversity Conservation
Authors: Squires Dale , Lent Rebecca , Dutton Peter H. , Dagorn Laurent , Ballance Lisa T.
Published: May 2021

Credit systems for mitigation of bycatch and habitat impact, incentive-based approaches, incentivize changes in fishery operator behavior and decision-making and allow flexibility in a least-cost method. Three types of credit systems, originally developed to address environmental pollution, are presented and evaluated as currently underutilized incentive-based approaches. The first, a cap-and-trade approach, evolved out of direct regulation through restricted limits with flexibility through the creation of tradeable unused portion of the limit, called credits. The second, a penalty-reward system, incentivizes bycatch- and habit-impact- reducing vessel behavior through rewards for positive behavior, and penalties for negative behavior. The third is a hybrid of the first two. All three systems can be used in the context of both absolute (fixed) and relative (rate-based or proportional) credits. Transferable habitat impact credit systems are developed for area management. The cap-and-trade credit system is directly compared to a comparable property rights system in terms of characteristics, strengths, weakness, and applicability. The Scottish Conservation Scheme and halibut bycatch reduction in the Alaskan multispecies groundfish fishery provide real-world examples of success with credit systems. The strengths, weaknesses, and applicability of credit systems are summarized, along with a set of recommendations. Cap-and-trade credit systems provide an important alternative to property rights, such as when rights are not feasible, and for this reason should prove useful for international fisheries. Penalty-reward and hybrid credit systems can substitute for cap-and-trade credit systems or property rights or complement them by addressing a related but otherwise unaddressed issue.
Does Nitrate Enrichment Accelerate Organic Matter Turnover in Subterranean Estuaries?
Authors: Ibánhez J. Severino P. , Álvarez-Salgado Xosé Antón , Rocha Carlos
Published: May 2021

Due to the widespread pollution of coastal groundwaters with fertilizers, submarine groundwater discharge (SGD) is often thought to be a large dissolved inorganic nitrogen (DIN) source to the ocean. Whether this N is autochthonous or allochthonous to the subterranean estuary (STE), the availability of large quantities of DIN can nevertheless interact with the cycling of other elements, such as carbon (C). In previous studies, we documented the discharge of large quantities of freshwater and NO3– from the mouth of an STE into the Ria Formosa lagoon (SW Iberian Peninsula). For the period covered in this study (2009–2011), the same STE site was dominated by recirculating seawater due to a prolonged fall in piezometric head in the coupled coastal aquifers. Total SGD rates remained similarly high, peaking at 144 cm day–1 at the lower intertidal during fall. We observed a progressive increase of NO3– availability within the STE associated with the recovery of piezometric head inland. Interestingly, during this period, the highest SGD-derived dissolved organic C and DIN fluxes (112 ± 53 and 10 ± 3 mmol m–2 day–1, respectively) originated in the lower intertidal. NO3– enrichment in the STE influences the benthic reactivity of fluorescent dissolved organic matter (FDOM): when seawater recirculation drives STE dynamics, only small changes in the benthic distribution of recalcitrant humic-like FDOM are observed (from −2.57 ± 1.14 to 1.24 ± 0.19 10–3 R.U. “bulk” sediment h–1) in the absence of DIN. However, when DIN is available, these recalcitrant fractions of FDOM are actively generated (from 1.32 ± 0.15 to 11.56 ± 3.39 10–3 R.U. “bulk” sediment h–1), accompanied by the production of labile protein-like FDOM. The results agree with previous studies conducted with flow-through reactor experiments at the same site and suggest that DIN enrichment in the STE enhances the metabolic turnover of sedimentary organic matter up to the point of discharge to surface waters. DIN pollution of coastal aquifers may therefore promote a contraction of the residence time of particulate organic C within the STE, driving carbon from continental storage into the sea.
Modelling the Effects of Traits and Abiotic Factors on Viral Lysis in Phytoplankton
Authors: Flynn Kevin J. , Kimmance Susan A. , Clark Darren R. , Mitra Aditee , Polimene Luca , Wilson William H.
Published: May 2021

A mechanistic system dynamics description is developed of the interactions between a single lytic-virus – phytoplankton-host couple. The model has state variables for virus, uninfected and infected host biomass, and describes virus and host allometry and physiology. The model, analogous to experimental laboratory virus-host systems but more amenable to hypothesis testing, enables us to explore the relative importance of some of the poorly understood factors suspected to impact plankton virus-host dynamics. Model behaviour is explored with respect to abiotic factors (light, mixed layer depth, nutrient and suspended particle loading), host traits (size, growth rate, motility) and virus traits (size, latent period and burst size including linkage to compromised host physiology, and decay rates). Simulations show that the optimal performance of a virus (i.e., optimal trait characterisation) is a function of many factors relating to the virus, its host, and the environment. In general, smaller viruses and smaller motile hosts give rise to more productive infection outcomes that result in rapid demise of the host and high post-infection virus abundance. However, the timing of the development of the interaction (relative abundance of virus to host at the start of rapid host population growth), overlain on the growth rate and physiological status of the host, was seen to be critical. Thus, for any one configuration of the model, the inoculum level of the virus (multiplicity of infection- MOI) displayed an optimum time-point between the infection developing too quickly, limiting biomass accumulation, or too late so that nutrient or light limitation compromised host physiology and hence the burst size. Importantly, the success of an infection depended also upon the suspended particle load which, if high enough, adsorbs so many viruses that the infection does not develop. We conclude that adding viruses to plankton ecosystem models in a realistic fashion is a complicated process due to the way that the individual and coupled virus-host processes interact with the environment.
iOntoBioethics: A Framework for the Agile Development of Bioethics Ontologies in Pandemics, Applied to COVID-19
Authors: Odeh Mohammed , Kharbat Faten F. , Yousef Rana , Odeh Yousra , Tbaishat Dina , Hakooz Nancy , Dajani Rana , Mansour Asem
Published: May 2021

Background: Few ontological attempts have been reported for conceptualizing the bioethics domain. In addition to limited scope representativeness and lack of robust methodological approaches in driving research design and evaluation of bioethics ontologies, no bioethics ontologies exist for pandemics and COVID-19. This research attempted to investigate whether studying the bioethics research literature, from the inception of bioethics research publications, facilitates developing highly agile, and representative computational bioethics ontology as a foundation for the automatic governance of bioethics processes in general and the COVID-19 pandemic in particular.

Research Design: The iOntoBioethics agile research framework adopted the Design Science Research Methodology. Using systematic literature mapping, the search space resulted in 26,170 Scopus indexed bioethics articles, published since 1971. iOntoBioethics underwent two distinctive stages: (1) Manually Constructing Bioethics (MCB) ontology from selected bioethics sources, and (2) Automatically generating bioethics ontological topic models with all 26,170 sources and using special-purpose developed Text Mining and Machine-Learning (TM&ML) engine. Bioethics domain experts validated these ontologies, and further extended to construct and validate the Bioethics COVID-19 Pandemic Ontology.

Results: Cross-validation of the MCB and TM&ML bioethics ontologies confirmed that the latter provided higher-level abstraction for bioethics entities with well-structured bioethics ontology class hierarchy compared to the MCB ontology. However, both bioethics ontologies were found to complement each other forming a highly comprehensive Bioethics Ontology with around 700 concepts and associations COVID-19 inclusive.

Conclusion:The iOntoBioethics framework yielded the first agile, semi-automatically generated, literature-based, and domain experts validated General Bioethics and Bioethics Pandemic Ontologies Operable in COVID-19 context with readiness for automatic governance of bioethics processes. These ontologies will be regularly and semi-automatically enriched as iOntoBioethics is proposed as an open platform for scientific and healthcare communities, in their infancy COVID-19 learning stage. iOntoBioethics not only it contributes to better understanding of bioethics processes, but also serves as a bridge linking these processes to healthcare systems. Such big data analytics platform has the potential to automatically inform bioethics governance adherence given the plethora of developing bioethics and COVID-19 pandemic knowledge. Finally, iOntoBioethics contributes toward setting the first building block for forming the field of “Bioethics Informatics”.
Age and Interleukin-15 Levels Are Independently Associated With Intima-Media Thickness in Obesity-Related NAFLD Patients
Authors: Tarantino Giovanni , Citro Vincenzo , Balsano Clara , Capone Domenico
Published: May 2021

Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34–53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15. Anthropometric measures, metabolic profile, and serum inflammatory markers, as well as the levels of IL-15, MCP-1, b FGF, and GM-CSF, were analyzed by a bead-based assay. IMT, HS, subcutaneous, and visceral adipose tissues were detected by ultrasonography. The IL-15 levels of the obese patients were increased with respect to those of 44 young healthy subjects, i.e., 2.77 (1.21–4.8) vs. 1.55 (1–2.4) pg/mL (P = 0.002). In the univariate analysis, IL-15 levels were associated to IMT and to those of MCP-1, b FGF, and GM-CSF, without any relation to other inflammatory markers such as CRP and ferritin, except fibrinogen. In the multivariate analysis, after adjusting the HS severity for the extent of visceral adiposity, a dramatic change in prediction of IMT by HS was shown (β from 0.29 to 0.10, P from 0.008 to 0.37). When the visceral adipose tissue was combined with IL-15, on the one hand, and the well-known coronary artery disease (CAD) risk factors—i.e., age, gender, smoking status, HDL-cholesterol concentrations, triglycerides levels, and HOMA—on the other, only age and IL-15 remained the predictors of IMT (β = 0.60, P = 0.0001 and β = 0.25, P = 0.024, respectively). There was no association of IL-15 with various anthropometric parameters nor with body fat distribution and severity of HS, also after adjusting for age. Age is resulted to be the main factor in the prediction of IMT and thus of early atherosclerosis. The prediction of IMT by IL-15 coupled with the lack of prediction by the well-known CAD risks is in agreement with recent data, which emphasizes the main role of the immune system in the onset/worsening of atherosclerosis, even though the role of visceral adiposity should be further deepened. Age and IL-15 levels were both predictors of early atherosclerosis in this population of obese patients with NAFLD, suggesting a possible role of this cytokine in the atherosclerosis process.
M2 Macrophage Subpopulations in Glomeruli Are Associated With the Deposition of IgG Subclasses and Complements in Primary Membranous Nephropathy
Authors: Hu Wenxue , Li Guanglan , Lin Jieshan , Dong Wei , Yu Feng , Liu Wei , Wu Yanhua , Hao Wenke , Liang Xinling
Published: May 2021

Objectives: The role of M2 macrophages in the pathogenesis and progression of primary membranous nephropathy (PMN) remains unknown. In this study, we aimed to investigate the relationship between M2 subsets and clinicopathological features of patients with PMN.

Methods: A total of 55 patients with PMN confirmed by biopsy were recruited. The clinical and pathological data were recorded, respectively. Immunohistochemistry was used to detect the markers of M2 macrophages, including total macrophages (CD68+), M2a (CD206+), M2b (CD86+) and M2c (CD163+).

Results: The numbers of glomerular macrophages, M2a, M2b, and M2c macrophages were 1.83 (1.00, 2.67), 0.65 (0.15, 1.15), 0.67 (0.33, 1.50), and 0.80 (0.05, 2.30) per glomerulus, respectively. Higher number of glomerular macrophages was found in stage II compared with stage III (2.08 vs. 1.16, P = 0.008). These macrophages also were negatively correlated with serum albumin level (r = −0.331, P = 0.014), while positively associated with complement 3 (C3) deposition (r = 0.300, P = 0.026) and the severity of glomerulosclerosis (r = 0.276, P = 0.041). Moreover, glomerular M2a macrophages were significantly correlated with the deposition of C3 (r = 0.300, P = 0.026), immunoglobulin G1 (IgG1) (r = 0.339, P = 0.011), immunoglobulin G2 (IgG2) (r = 0.270, P = 0.046) and immunoglobulin G3 (IgG3) (r = 0.330, P = 0.014) in glomerular basement membrane (GBM). In addition, M2b macrophages were positively associated with IgG1 (r = 0.295, P = 0.029) and IgG2 (r = 0.393, P = 0.003), while M2c macrophages were negatively correlated with complement 4d (C4d) (r = −0.347, P = 0.009) in GBM.

Conclusions: Our results showed that M2 macrophage subpopulations in glomeruli are associated with the deposition of IgG subclasses and complements in renal tissue of PMN, which indicate that M2 macrophages may be involved in the pathogenesis and progression of PMN. Moreover, M2a and M2c macrophages might show different tendencies in the pathogenesis of PMN.