bluuebunny/crossref_metadata_2025 huggingface dataset:
Decadal variation of the relationship between the previous autumn IOD and the South China Sea summer monsoon
Authors: Zheng Meiying , Xu Feng , Liu Shengyuan , Li Yongchi , Zhang Shaojing , Yang Jinyi
Published: March 2023

Using reanalysis data from the ECMWF and Hadley Centre of the UK Meteorological Office, the present study analyzes the relationship between Indian Ocean Dipole (IOD) in the previous autumn (September–November) and South China Sea Summer (June–August) Monsoon (SCSSM) from 1951 to 2021. It is found that the relationship between the two indices was significantly enhanced from the late 1970s to the beginning of the 21st century, with a significant resonance cycle of 2–4a. The previous autumn IOD forced the Gill pattern in the upper troposphere by changing the Sea Surface Temperature Anomaly (SSTA) of the following summer in the Tropical Indian Ocean (TIO), resulting in the anticyclonic circulation anomaly in the Philippine Sea. It eventually alters the southwest monsoon near the South China Sea and the Philippine Sea. However, for a decade or more, as the Pacific Decadal Oscillation (PDO) phase turns from warm to cold and the relationship between El Niño–Southern Oscillation (ENSO) and IOD weakens, the impact of the previous autumn IOD on Indian Ocean SSTA in the summer of the following year weakens, resulting in a decrease in the correlation between the previous autumn IOD and SCSSM. The impact of the previous autumn’s Indian Ocean SSTA on the following year’s SCSSM is more considered in terms of the eastern Bay of Bengal and the Somali Sea basin. In addition, during the warm phase of PDO, the IOD of the previous autumn can cause abnormal summer precipitation in South China by strengthening or weakening the Western Pacific Subtropical High (WPSH) of the following summer, but there is no significant effect in the cold phase of PDO.
Stress levels, coping strategies, and mental health literacy among secondary school students in Kenya
Authors: Ayiro Lilian , Misigo Bernard Lushya , Dingili Rodgers
Published: March 2023

Introduction

Mental health literacy could be a protector from stress and other mental health problems. Statistics in sub-Saharan Africa estimate that up to 20% of children and adolescents experience mental health problems due to stress. Research has also shown that there is a bidirectional association between positive coping and mental health literacy. Nonetheless, little is known about stress levels, coping strategies, and mental health literacy of secondary school students in Kenya. This study sought to answer the following questions: What is the stress level of students in secondary schools in Kenya? What is the association between stress levels and coping strategies of learners? What is the mental health literacy level of learners in secondary schools in Kenya?

Methods

The study employed a sequential explanatory mixed methods research design by carrying out a quantitative study to ascertain stress levels and coping strategies and a qualitative study to explore the mental health literacy of the students. A total of 400 secondary school students aged 16–22 years participated in the study. Quantitative data were analyzed using descriptive and inferential statistics whereas qualitative data was analyzed thematically.

Results

Based on these results, the majority of students were moderately 244 (66%) and highly 112 (31%) stressed. Only 11 students (3%) reported low stress levels. The study also indicated a positive significant association between stress and avoidance coping strategy (r = 0.11, p < 0.05). Qualitative data revealed varied conceptualizations of mental health. The following themes emerged: the students conceptualized mental health as help offered to people who are stressed to help them reduce stressors, others felt that it was a state of being at peace with one’s self and being able to think and act soundly, whereas others felt that mental health is severe mental disorder or illness. Students further attributed stress to school, peer, and home pressure.

Discussion

Lastly, although the students believed that seeking emotional, social, and psychological support was the best way to cope with stress, they feared seeking this support from teachers and peers. There was no evidence of students seeking support from parents. This study contributes to the Group Socialization Theory that suggests that peers become the primary social agents of adolescents outside the confinement of their homes. It provides essential information for developing awareness programs on mental health issues in Kenyan secondary schools. It also highlights a need to equip students with skills so that they can offer peer-to-peer support in times of distress.
The effect of a formative assessment practice on student achievement in mathematics
Authors: Boström Erika , Palm Torulf
Published: March 2023

Research has shown that formative assessment can enhance student learning. However, it is conceptualised and implemented in different ways, and its effects on student achievement vary. A need has been identified for experimental studies to carefully describe both the characteristics of implemented formative assessment practices and their impact on student achievement. We examined the effects on student achievement of changes in formative assessment of a random sample of 14 secondary school mathematics teachers after a professional development programme. This study describes practices implemented and students’ achievement as measured by pre-tests and post-tests. We found no significant differences in achievement on the post-test, after controlling for pre-test scores, between the intervention group and control group, and no significant correlation between the number of formative assessment activities implemented and the post-test scores (controlled for the pre-test scores). We discuss characteristics of formative assessment implementations that may be critical for enhancing student achievement.
Using Minecraft to cultivate student interest in STEM
Authors: Tablatin Christine Lourrine S. , Casano Jonathan D. L. , Rodrigo Maria Mercedes T.
Published: March 2023

Due to the popularity and flexibility of Minecraft, educators have used this game to develop instructional materials and activities to cultivate student interests in science, technology, engineering and mathematics (STEM). One example of such an initiative is the What-If Hypothetical Implementations in Minecraft (WHIMC) project of the University of Illinois Urbana Champaign. The study reported in this paper describes a WHIMC deployment in the Philippines and the effects this deployment had on student STEM interest. The study used quantitative and qualitative methods to determine the effect of WHIMC on the STEM interest of Filipino students. We performed quantitative analysis of the pre- and post-STEM Interest Questionnaire (SIQ) ratings and Game Experience Questionnaire (GEQ) ratings of the high- and low-performers to determine the effect of using WHIMC in the students’ STEM interest and the difference between the game experience of high- and low-performers, respectively. Qualitative analysis of the answers to the open-ended questions about the attributes of the module was also conducted to determine the relationship between the module attributes and student performance. The analysis of the aggregated SIQ ratings before and after using the WHIMC-based modules revealed only a minimal effect on the STEM interests of the students. However, there was a significant effect in the Choice Actions construct, which implies that students recognize the importance of studying hard if they want to pursue STEM-related careers. Further, the analysis of the overall GEQ of high-performers and low-performers also revealed no significant difference. Although no significant difference was observed in the overall GEQ, high-performers had significantly higher GEQ ratings in the Immersion dimension. This result suggested that high-performers had a more positive, engaging, and enjoyable learning experience. Moreover, the findings on the favorite module attributes suggested that students perform better in the out-of-game assessments when they like all the module attributes. This implies that students must be engaged in the game and learning task aside from being interested in the learning topic to have better assessment scores. The study also showed that open-ended learning environments coupled with tasks that demand exploration, observation, and higher-ordered thinking are demanding even on high-performers.
Integrative network-based analysis on multiple Gene Expression Omnibus datasets identifies novel immune molecular markers implicated in non-alcoholic steatohepatitis
Authors: Zhang Jun-jie , Shen Yan , Chen Xiao-yuan , Jiang Man-lei , Yuan Feng-hua , Xie Shui-lian , Zhang Jie , Xu Fei
Published: March 2023

Introduction

Non-alcoholic steatohepatitis (NASH), an advanced subtype of non-alcoholic fatty liver disease (NAFLD), has becoming the most important aetiology for end-stage liver disease, such as cirrhosis and hepatocellular carcinoma. This study were designed to explore novel genes associated with NASH.

Methods

Here, five independent Gene Expression Omnibus (GEO) datasets were combined into a single cohort and analyzed using network biology approaches.

Results

11 modules identified by weighted gene co-expression network analysis (WGCNA) showed significant association with the status of NASH. Further characterization of four gene modules of interest demonstrated that molecular pathology of NASH involves the upregulation of hub genes related to immune response, cholesterol and lipid metabolic process, extracellular matrix organization, and the downregulation of hub genes related to cellular amino acid catabolic, respectively. After DEGs enrichment analysis and module preservation analysis, the Turquoise module associated with immune response displayed a remarkably correlation with NASH status. Hub genes with high degree of connectivity in the module, including CD53, LCP1, LAPTM5, NCKAP1L, C3AR1, PLEK, FCER1G, HLA-DRA and SRGN were further verified in clinical samples and mouse model of NASH. Moreover, single-cell RNA-seq analysis showed that those key genes were expressed by distinct immune cells such as microphages, natural killer, dendritic, T and B cells. Finally, the potential transcription factors of Turquoise module were characterized, including NFKB1, STAT3, RFX5, ILF3, ELF1, SPI1, ETS1 and CEBPA, the expression of which increased with NASH progression.

Discussion

In conclusion, our integrative analysis will contribute to the understanding of NASH and may enable the development of potential biomarkers for NASH therapy.
The specific mitochondrial unfolded protein response in fast- and slow-twitch muscles of high-fat diet-induced insulin-resistant rats
Authors: Li Can , Li Nan , Zhang Ziyi , Song Yu , Li Jialin , Wang Zhe , Bo Hai , Zhang Yong
Published: March 2023

Introduction

Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR.

Methods

Male Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiber-enriched tibialis anterior (TA) under HFD conditions.

Results

Our results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fast-twitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding.

Conclusion

The expression of proteins involved in glucose transport in slow-twitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance.
Learning new attack vectors from misuse cases with deep reinforcement learning
Authors: Veith Eric M. S. P. , Wellßow Arlena , Uslar Mathias
Published: March 2023

Modern smart grids already consist of various components that interleave classical Operational Technology (OT) with Information and Communication Technology (ICT), which, in turn, have opened the power grid to advanced approaches using distributed software systems and even Artificial Intelligence (AI) applications. This IT/OT integration increases complexity, however, without argument, this advance is necessary to accommodate the rising numbers of prosumers, Distributed Energy Resources (DERs), to enable new market concepts, and to tackle world-wide CO2 emission goals. But the increasing complexity of the Critical National Infrastructure (CNI) power grid gives way to numerous new attack vectors such that a priori robustness cannot be guaranteed anymore and run-time resilience, especially against the “unknown unknowns”, is the focus of current research. In this article, we present a novel combination of so called misuse-case modelling and an approach based on Deep Reinforcement Learning (DRL) to analyze a power grid for new attack vectors. Our approach enables learning from domain knowledge (offline learning), while expanding on that knowledge through learning agents that eventually uncover new attack vectors.
Bi-level energy management strategy for power-split plug-in hybrid electric vehicles: A reinforcement learning approach for prediction and control
Authors: Yang Xueping , Jiang Chaoyu , Zhou Ming , Hu Hengjie
Published: March 2023

The implementation of an energy management strategy plays a key role in improving the fuel economy of plug-in hybrid electric vehicles (PHEVs). In this article, a bi-level energy management strategy with a novel speed prediction method leveraged by reinforcement learning is proposed to construct the optimization scheme for the inner energy allocation of PHEVs. First, the powertrain transmission model of the PHEV in a power-split type is analyzed in detail to obtain the energy routing and its crucial characteristics. Second, a Q-learning (QL) algorithm is applied to establish the speed predictor. Third, the double QL algorithm is introduced to train an effective controller offline that realizes the optimal power distribution. Finally, given a reference battery's state of charge (SOC), a model predictive control framework solved by the reinforcement learning agent with a novel speed predictor is proposed to build the bi-level energy management strategy. The simulation results show that the proposed method performs with a satisfying fuel economy in different driving scenarios while tracking the corresponding SOC references. Moreover, the calculation performance also implies the potential online capability of the proposed method.
Structure and biogeochemical process of microaggregates in a water source area of China’s South-to-North Water Diversion Project according to different land use types
Authors: Li Chunjie , Guo Shili , Shang Songhao , Qi Pengcheng , Li Bailian
Published: March 2023

Soil biogeochemical processes have the potential to impact water quality in source areas of water diversion projects. This study aimed to explore the differences in biochemical processes and mechanisms at the microaggregate scale for different land use types in the water source area of China's Middle Route of the South-to-North Water Diversion Project. The study compared four typical land use types—forests, shrublands, terraces, and cultivated land—by characterizing the microaggregates using various analytical techniques, including scanning electron microscopy (SEM), SEM-EDS plane scan analysis, X-ray diffraction (XRD), X-ray fluorescence (XRF) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. Microaggregates from forests and shrublands had a flocculent spatial structure, while those from terraces had a nondirectional plate-like spatial structure, and those from cultivated land had a laminar spatial structure. Additionally, elements such as Mg, Al, and Fe were enriched in clay particles when combined with microaggregates. The mineral composition of clay varied significantly between different land use practices, with illite, chlorite, anorthite, albite, and quartz present in higher proportions in terraces and cultivated land than in forests and shrublands. Moreover, the contents of transitional elements such as Ti, Fe, Zn, Y, and Zr increased with each successive land use practice. Soil organic matter (SOM) was observed to decline in the order of forest > shrubland > terraces > cultivated land. Over-tillage appeared to be the primary mechanism of organic matter loss due to long-term tillage. The results of this study provide valuable insights into soil erosion and chemical transport dynamics. The mineral composition and spatial structure of microaggregates are important determinants of soil biochemical processes and mechanisms, which can influence water quality. The findings suggest that forest and shrubland management practices may be more conducive to maintaining soil health and water quality in source areas of water diversion projects.
Characterizing eastern spruce budworm’s large-scale dispersal events through flight behavior and stable isotope analyses
Authors: Dargent Felipe , Candau Jean-Noël , Studens Kala , Perrault Kerry H. , Reich Megan S. , Bataille Clement Pierre
Published: March 2023

Eastern spruce budworm moth (Choristoneura fumiferana (Clem.)) mass outbreaks have widespread economic and ecological consequences. A key explanation for the large-scale spread and synchronization of these outbreaks is the long-distance dispersal (up to 450 km) of moths from hotspots (high-density populations) to lower-density areas. These events have proved difficult to monitor because dispersal flights occur only a few times a year, have no consistent routes, and commonly used tracking methods (e.g., population genetics, mark-recapture, radio telemetry) are inadequate for this system. Confirming immigration and distinguishing between local and immigrant individuals are crucial steps in identifying the physical and ecological drivers of moth dispersal. Here, we test whether isotopes of hydrogen (i.e., delta notation: δ2H) and strontium (i.e., strontium isotope ratios: 87Sr/86Sr), known to independently vary in space in a predictable manner, can be used to show that an immigration event occurred and to distinguish between local and immigrant adult spruce budworm moths. We used an automated pheromone trap system to collect individuals at six different sites in eastern Canada within and outside the current outbreak area of budworm moths. We first use moth flight behavior and time of capture, currently the best available tool, to determine putative local vs. immigrant status, and then evaluate whether individual 87Sr/86Sr and δ2H differ between putative classes. At two sites, we detect immigrant individuals that differ significantly from putative locals and thus confirm immigration has occurred. Saliently, sites where putative locals were sampled before the occurrence of potential immigration events (~10 days) showed the strongest differences between immigrant individuals’ and local 87Sr/86Sr and δ2H values. Sites where the collection of putative locals was close in time (hours) or following an immigration event (days) had a less-clear distinction between putative immigrants and locals, and showed signs of mixing between these two groups. We speculate that recent immigration could have led to the misclassification of immigrants as putative locals. 87Sr/86Sr and δ2H data generally support the adequacy of current approaches using capture-time to detect immigration events, and provide enhanced resolution to distinguish between local and immigrant individuals and to confirm an immigration event. We discuss the broader implication of adding isotopes to the toolkit to monitor spruce budworm dispersal and suggest next steps in implementing these tools.
Spatial-temporal evolution and driving factors of water yield in three major drainage basins of Hainan Island based on land use change
Authors: Lei Jinrui , Zhang Le , Wu Tingtian , Chen Xiaohua , Li Yuanling , Chen Zongzhu
Published: March 2023

Tropical rainforests in the central hilly section of Hainan Island are the source of the Nandu, Changhua, and Wanquan rivers, which are crucial for water conservation and ecological protection. The quantitative assessment of water yield in the three basins is beneficial for developing regional water resource protection plans, establishing ecological compensation mechanisms, and maintaining ecological balance. Based on land use data from five periods between 1980 and 2020, this paper adopts the InVEST model and geographic detectors to investigate the spatial-temporal variation characteristics and driving factors of water yield in three major basins of Hainan Island. The results demonstrate that forestland, which makes up more than 70% of the total area in the three basins of Hainan Island, is the predominant land use type. With a depth of 1269.18 mm, Wanquan Basin is the deepest of the three basins, followed by Nandu Basin and Changhua Basin. The total water yield of three basins shows a slightly decreasing trend from 17.991 billion m3 in 1980 to 17.864 billion m3 in 2020. The spatial distribution of water yield is high in the southeast region and low in the northwest region, with strong autocorrelation and significant aggregation. According to geographic detection, land use type is the dominant factor for the spatial differentiation of water yield in the three basins, with a contribution rate of 0.563, and soil type and annual precipitation are important impact factors. The interaction and synergy of soil types and land use types jointly affect the spatial differentiation of water yield in the basin. The results of this study can provide data support and scientific references for biodiversity conservation and ecosystem restoration in the three major basins of Hainan Island.
Development and validation of a tumor immune cell infiltration-related gene signature for recurrence prediction by weighted gene co-expression network analysis in prostate cancer
Authors: Xie Lin-Ying , Huang Han-Ying , Hao Yu-Lei , Yu Miaomiao , Zhang Wenju , Wei Enwei , Gao Chunfeng , Wang Chang , Zeng Lei
Published: March 2023

Introduction: Prostate cancer (PCa) is the second most common malignancy in men. Despite multidisciplinary treatments, patients with PCa continue to experience poor prognoses and high rates of tumor recurrence. Recent studies have shown that tumor-infiltrating immune cells (TIICs) are associated with PCa tumorigenesis.

Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to derive multi-omics data for prostate adenocarcinoma (PRAD) samples. The CIBERSORT algorithm was used to calculate the landscape of TIICs. Weighted gene co-expression network analysis (WGCNA) was performed to determine the candidate module most significantly associated with TIICs. LASSO Cox regression was applied to screen a minimal set of genes and construct a TIIC-related prognostic gene signature for PCa. Then, 78 PCa samples with CIBERSORT output p-values of less than 0.05 were selected for analysis. WGCNA identified 13 modules, and the MEblue module with the most significant enrichment result was selected. A total of 1143 candidate genes were cross-examined between the MEblue module and active dendritic cell-related genes.

Results: According to LASSO Cox regression analysis, a risk model was constructed with six genes (STX4, UBE2S, EMC6, EMD, NUCB1 and GCAT), which exhibited strong correlations with clinicopathological variables, tumor microenvironment context, antitumor therapies, and tumor mutation burden (TMB) in TCGA-PRAD. Further validation showed that the UBE2S had the highest expression level among the six genes in five different PCa cell lines.

Discussion: In conclusion, our risk-score model contributes to better predicting PCa patient prognosis and understanding the underlying mechanisms of immune responses and antitumor therapies in PCa.
Potential predictive value of circulating tumor DNA (ctDNA) mutations for the efficacy of immune checkpoint inhibitors in advanced triple-negative breast cancer
Authors: Tan Qiaorui , Chi Yajing , Su Mu , Zhou Jinxing , Zhou Dongdong , Zheng Fangchao , Man Xiaochu , Sun Shujuan , Huang Jie , Li Huihui
Published: March 2023

Background: In recent years, tumor immunotherapy has become a viable treatment option for triple negative breast cancer (TNBC). Among these, immune checkpoint inhibitors (ICIs) have demonstrated good efficacy in advanced TNBC patients with programmed death-ligand 1 (PD-L1) positive expression. However, only 63% of PD-L1-positive individuals showed any benefit from ICIs. Therefore, finding new predictive biomarkers will aid in identifying patients who are likely to benefit from ICIs. In this study, we used liquid biopsies and next-generation sequencing (NGS) to dynamically detect changes in circulating tumor DNA (ctDNA) in the blood of patients with advanced TNBC treated with ICIs and focused on its potential predictive value.

Methods: From May 2018 to October 2020, patients with advanced TNBC treated with ICIs at Shandong Cancer Hospital were included prospectively. Patient blood samples were obtained at the pretreatment baseline, first response evaluation, and disease progression timepoints. Furthermore, 457 cancer-related genes were evaluated by NGS, and patients’ ctDNA mutations, gene mutation rates, and other indicators were determined and coupled with clinical data for statistical analysis.

Results: A total of 11 TNBC patients were included in this study. The overall objective response rate (ORR) was 27.3%, with a 6.1-month median progression-free survival (PFS) (95% confidence interval: 3.877–8.323 months). Of the 11 baseline blood samples, 48 mutations were found, with the most common mutation types being frame shift indels, synonymous single-nucleotide variations (SNVs), frame indel missenses, splicing, and stop gains. Additionally, univariate Cox regression analysis revealed that advanced TNBC patients with one of 12 mutant genes (CYP2D6 deletion and GNAS, BCL2L1, H3F3C, LAG3, FGF23, CCND2, SESN1, SNHG16, MYC, HLA-E, and MCL1 gain) had a shorter PFS with ICI treatment (p < 0.05). To some extent, dynamic changes of ctDNA might indicate the efficacy of ICIs.

Conclusion: Our data indicate that ICI efficacy in patients with advanced TNBC may be predicted by 12 mutant ctDNA genes. Additionally, dynamic alterations in peripheral blood ctDNA might be used to track the effectiveness of ICI therapy in those with advanced TNBC.
Characteristics of malignant tumors of digestive system and autoimmune diseases
Authors: Yin Hang , Li Qun
Published: March 2023

With the development of preoperative examination technology, endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNA) has been widely used in preoperative pathological diagnosis. However, challenges remain in obtaining appropriate tissue samples and obtaining accurate pathological results to predict disease risk. Therefore, this study aimed to analyze the characteristics of digestive system malignancies and their autoimmune diseases, and to analyze the clinicopathological features, preoperative CT imaging features and pathological grades of pNENs of different pathological degrees of pNENs on the prognosis of pNENs. Experimental results showed that non-functioning pancreatic neuroendocrine tumors showed prominent surrounding hypervascular lesions on multiphase CT examination. Among them, arterial phase and portal venous phase were most clearly imaged at the end, and the degree of local vascular invasion could be used as an index to evaluate its resectability. The sensitivity of CT examination was 63% to 82%, and the specificity was 83% to 100%, depending on the size.
Exploration of genotype-by-environment interactions affecting gene expression responses in porcine immune cells
Authors: Murani Eduard , Hadlich Frieder
Published: March 2023

As one of the keys to healthy performance, robustness of farm animals is gaining importance, and with this comes increasing interest in genetic dissection of genotype-by-environment interactions (G×E). Changes in gene expression are among the most sensitive responses conveying adaptation to environmental stimuli. Environmentally responsive regulatory variation thus likely plays a central role in G×E. In the present study, we set out to detect action of environmentally responsive cis-regulatory variation by the analysis of condition-dependent allele specific expression (cd-ASE) in porcine immune cells. For this, we harnessed mRNA-sequencing data of peripheral blood mononuclear cells (PBMCs) stimulated in vitro with lipopolysaccharide, dexamethasone, or their combination. These treatments mimic common challenges such as bacterial infection or stress, and induce vast transcriptome changes. About two thirds of the examined loci showed significant ASE in at least one treatment, and out of those about ten percent exhibited cd-ASE. Most of the ASE variants were not yet reported in the PigGTEx Atlas. Genes showing cd-ASE were enriched in cytokine signaling in immune system and include several key candidates for animal health. In contrast, genes showing no ASE featured cell-cycle related functions. We confirmed LPS-dependent ASE for one of the top candidates, SOD2, which ranks among the major response genes in LPS-stimulated monocytes. The results of the present study demonstrate the potential of in vitro cell models coupled with cd-ASE analysis for the investigation of G×E in farm animals. The identified loci may benefit efforts to unravel the genetic basis of robustness and improvement of health and welfare in pigs.
Neutrophilic inflammation promotes SARS-CoV-2 infectivity and augments the inflammatory responses in airway epithelial cells
Authors: Calvert Ben A. , Quiroz Erik J. , Lorenzana Zareeb , Doan Ngan , Kim Seongjae , Senger Christiana N. , Anders Jeffrey J. , Wallace Wiliam D. , Salomon Matthew P. , Henley Jill , Ryan Amy L.
Published: March 2023

Introduction

In response to viral infection, neutrophils release inflammatory mediators as part of the innate immune response, contributing to pathogen clearance through virus internalization and killing. Pre- existing co-morbidities correlating to incidence to severe COVID-19 are associated with chronic airway neutrophilia. Furthermore, examination of COVID-19 explanted lung tissue revealed a series of epithelial pathologies associated with the infiltration and activation of neutrophils, indicating neutrophil activity in response to SARS-CoV-2 infection.

Methods

To determine the impact of neutrophil-epithelial interactions on the infectivity and inflammatory responses to SARS-CoV-2 infection, we developed a co-culture model of airway neutrophilia. This model was infected with live SARS-CoV-2 virus the epithelial response to infection was evaluated.

Results

SARS-CoV-2 infection of airway epithelium alone does not result in a notable pro-inflammatory response from the epithelium. The addition of neutrophils induces the release of proinflammatory cytokines and stimulates a significantly augmented proinflammatory response subsequent SARS-CoV-2 infection. The resulting inflammatory responses are polarized with differential release from the apical and basolateral side of the epithelium. Additionally, the integrity of the \epithelial barrier is impaired with notable epithelial damage and infection of basal stem cells.

Conclusions

This study reveals a key role for neutrophil-epithelial interactions in determining inflammation and infectivity.
IgA2 immune complexes selectively promote inflammation by human CD103+ dendritic cells
Authors: Mes Lynn , Steffen Ulrike , Chen Hung-Jen , Veth Jennifer , Hoepel Willianne , Griffith Guillermo Romeo , Schett Georg , den Dunnen Jeroen
Published: March 2023

While immunoglobulin A (IgA) is well known for its neutralizing and anti-inflammatory function, it is becoming increasingly clear that IgA can also induce human inflammatory responses by various different immune cells. Yet, little is known about the relative role of induction of inflammation by the two IgA subclasses i.e. IgA1, most prominent subclass in circulation, and IgA2, most prominent subclass in the lower intestine. Here, we set out to study the inflammatory function of IgA subclasses on different human myeloid immune cell subsets, including monocytes, and in vitro differentiated macrophages and intestinal CD103+ dendritic cells (DCs). While individual stimulation with IgA immune complexes only induced limited inflammatory responses by human immune cells, both IgA subclasses strongly amplified pro-inflammatory cytokine production upon co-stimulation with Toll-like receptor (TLR) ligands such as Pam3CSK4, PGN, and LPS. Strikingly, while IgA1 induced slightly higher or similar levels of pro-inflammatory cytokines by monocytes and macrophages, respectively, IgA2 induced substantially more inflammation than IgA1 by CD103+ DCs. In addition to pro-inflammatory cytokine proteins, IgA2 also induced higher mRNA expression levels, indicating that amplification of pro-inflammatory cytokine production is at least partially regulated at the level of gene transcription. Interestingly, cytokine amplification by IgA1 was almost completely dependent on Fc alpha receptor I (FcαRI), whilst blocking this receptor only partially reduced cytokine induction by IgA2. In addition, IgA2-induced amplification of pro-inflammatory cytokines was less dependent on signaling through the kinases Syk, PI3K, and TBK1/IKKϵ. Combined, these findings indicate that IgA2 immune complexes, which are most abundantly expressed in the lower intestine, particularly promote inflammation by human CD103+ intestinal DCs. This may serve an important physiological function upon infection, by enabling inflammatory responses by this otherwise tolerogenic DC subset. Since various inflammatory disorders are characterized by disturbances in IgA subclass balance, this may also play a role in the induction or exacerbation of chronic intestinal inflammation.
Comprehensive analysis of m6A RNA methylation modification patterns and the immune microenvironment in osteoarthritis
Authors: Liu Zhixin , Liu Heng , Li Deqiang , Ma Liang , Lu Tongxin , Sun Hao , Zhang Yuankai , Yang Hui
Published: March 2023

Background

Osteoarthritis (OA) is the most common joint degenerative disease, and so far, there is no effective therapy to prevent or delay its development. Considerable attention is now being given to the impact of m6A RNA methylation modification on the disease immune regulation. However, much remains unknown about the function of m6A modification in OA.

Methods

A total of 63 OA and 59 healthy samples were applied to comprehensively examine the m6A regulators mediated RNA methylation modification pattern in OA, and evaluate the impacts of distinct patterns on the characteristics of OA immune microenvironment, including immune infiltration cells, immune responses and human leukocyte antigen (HLAs) genes expression. In addition, we screened out the m6A phenotype-related genes and further explored their potential biological functions. At last, we verified the expression of key m6A regulators and their associations with immune cells, in vitro.

Results

Most of m6A regulators was differentially expressed in OA samples compared to the normal tissues. Based on six hub-m6A regulators identified as abnormally expressed in OA samples, we developed a classifier to distinguish OA patients from healthy individuals. We noted that immune characteristics of OA were correlated with m6A regulators. For instance, YTHDF2 had a strongest significantly positive correlation with regulatory T cells (Tregs) and IGFBP2 was strongest negatively associated with dendritic cells (DCs), which were confirmed by the immunohistochemistry (IHC) staining. Two distinct m6A modification patterns were determined: pattern B had higher infiltrating immunocytes and more active immune responses than pattern A, and two patterns differed in the expression of HLA genes. We also identified 1,592 m6A phenotype-related genes that could mediate the OA synovitis and cartilage degradation by the PI3K-Akt signaling pathway. Quantitative real-time polymerase chain reaction (qRT-PCR) results indicated that IGFBP2 was significantly overexpressed, while YTHDF2 mRNA expression was decreased in OA samples, which was consistent with our findings.

Conclusion

Our research proves the essential impact of m6A RNA methylation modification on the OA immune microenvironment, and helps to explain the regulatory mechanism behind it, which may open up a new direction for more precise immunotherapy of osteoarthritis.
A Multi-Mode Convolutional Neural Network to reconstruct satellite-derived chlorophyll-a time series in the global ocean from physical drivers
Authors: Roussillon Joana , Fablet Ronan , Gorgues Thomas , Drumetz Lucas , Littaye Jean , Martinez Elodie
Published: March 2023

Time series of satellite-derived chlorophyll-a concentration (Chl, a proxy of phytoplankton biomass), continuously generated since 1997, are still too short to investigate the low-frequency variability of phytoplankton biomass (e.g. decadal variability). Machine learning models such as Support Vector Regression (SVR) or Multi-Layer Perceptron (MLP) have recently proven to be an alternative approach to mechanistic ones to reconstruct Chl synoptic past time-series before the satellite era from physical predictors. Nevertheless, the relationships between phytoplankton and its physical surrounding environment were implicitly considered homogeneous in space, and training such models on a global scale does not allow one to consider known regional mechanisms. Indeed, the global ocean is commonly partitioned into biogeochemical provinces (BGCPs) into which phytoplankton growth is supposed to be governed by regionally-”homogeneous” processes. The time-evolving nature of those provinces prevents imposing a priori spatially-fixed boundary constraints to restrict the learning phase. Here, we propose to use a multi-mode Convolutional Neural Network (CNN), which can spatially learn and combine different modes, to globally account for interregional variabilities. Each mode is associated with a CNN submodel, standing for a mode-specific response of phytoplankton biomass to the physical forcing. Beyond improving performance reconstruction, we show that the different modes appear regionally consistent with the ocean dynamics and that they may help to get new insights into physical-biogeochemical processes controlling phytoplankton spatio-temporal variability at global scale.
A crustacean vitellogenin-derived peptide as an oocyte-specific delivery vehicle for gene silencing
Authors: Cohen Shany , Hasan Mahde , Frishman Noa , Khalaila Isam
Published: March 2023

Gene silencing by dsRNA is well documented in crustaceans, but RNA interference (RNAi) in developing oocytes is yet to be achieved. The main obstacle to RNAi in the oocytes of oviparous animals derives from their protective layers, including the cytosolic membrane, the vitelline envelope, and a layer of follicular cells. These layers form a barrier preventing the entry of large nonspecific molecules, such as double-stranded RNA (dsRNA). This article describes a sophisticated tool – designated OSDel [oocyte-specific delivery] – for the delivery of dsRNA for gene silencing in the developing oocyte. The methodology exploits the process of receptor-mediated endocytosis (RME) taking place in the crustacean female for internalizing vitellogenin (Vg) (the precursor of the major yolk protein, vitellin) into oocytes. In this process, the extracellular domain of the Vg receptor (VgR) interacts with a distinct amino acid sequence of Vg and internalizes it to form yolk droplets. Here, we tested the premise that a distinct 24 amino-acid peptide derived from Macrobrachium rosenbergii Vg (designated VgP) would interact with VgR to form particles of a size suitable for piggy-backing dsRNA into oocytes via RME. We found that fluorescently labeled VgP had a micromolar affinity for the ligand-binding domain (LBD) of the VgR and could indeed be delivered to and internalized in oocytes. As model system to illustrate the applicability of the OSDel, we injected vitellogenic females with dsRNA encoding the eye development gene PAX6 piggybacked on VgP. Proof that the dsRNA had been successfully internalized into the developing oocytes and had silenced the PAX6 gene was derived from impaired eye development in 87% of the embryos. The ability to manipulate embryos by simple injection into vitellogenic crustacean females may prove to be a powerful high throughput tool for functional genomics investigation in crustacean embryos and for silencing genes relevant to crustacean aquaculture and biotechnology.
Microbial dysbiosis precedes signs of sea star wasting disease in wild populations of Pycnopodia helianthoides
Authors: McCracken Andrew R. , Christensen Blair M. , Munteanu Daniel , Case B. K. M. , Lloyd Melanie , Herbert Kyle P. , Pespeni Melissa H.
Published: March 2023

Sea star wasting (SSW) disease, a massive and ongoing epidemic with unknown cause(s), has led to the rapid death and decimation of sea star populations with cascading ecological consequences. Changes in microbial community structure have been previously associated with SSW, however, it remains unknown if SSW-associated dysbiosis is a mechanism or artifact of disease progression, particularly in wild populations. Here, we compare the microbiomes of the sunflower sea star,Pycnopodia helianthoides, before (Naïve) and during (Exposed and Wasting) the initial outbreak in Southeast Alaska to identify changes and interactions in the microbial communities associated with sea star health and disease exposure. We found an increase in microbial diversity (both alpha and beta diversity) preceding signs of disease and an increase in abundance of facultative and obligate anaerobes (most notablyVibrio) in both Exposed (apparently healthy) and Wasting animals. Complementing these changes in microbial composition was the initial gain of metabolic functions upon disease exposure, and loss of function with signs of wasting. Using Bayesian network clustering, we found evidence of dysbiosis in the form of co-colonization of taxa appearing in large numbers among Exposed and Wasting individuals, in addition to the loss of communities associated with Naïve sea stars. These changes in community structure suggest a shared set of colonizing microbes that may be important in the initial stages of SSW. Together, these results provide several complementary perspectives in support of an early dysbiotic event preceding visible signs of SSW.
Dissolved rare earth elements in the Northwest Pacific: Sources, water mass tracing, and cross‐shelf fluxes
Authors: Cao Axiang , Zhang Jing , Zhang Honghai , Chen Zhaohui , Cui Guanghao , Liu Zhensong , Li Yanbin , Liu Qian
Published: March 2023

In the Northwest Pacific, a key area for understanding the sources and transport of materials in the ocean, knowledge of the sources, transport, and biogeochemical cycling of trace elements is limited. Trace elements such as the rare earth elements (REEs) can trace the sources and transport of water masses. Here we present dissolved REE concentrations along a longitudinal transect (150 oE) from 13°N to 40°N in the Northwest Pacific (≤2000 m). We divided the transect into two subregions: a mixed water region (MWR; 37~40 °N, where the Oyashio and Kuroshio currents mix) and a subtropical region (13~34 °N). In the MWR, REEs were strongly positively correlated with apparent oxygen utilization in subsurface water (depth > the chlorophyll maximum layer, potential density <26.6 kg/m3), with about a 4-fold higher slope (0.15±0.06) than in the subtropical region in subsurface and intermediate waters (0.04±0.003, potential density <27.5 kg/m3). This suggests that REEs are released by organic matter remineralization at a higher efficiency in the MWR vs. in the subtropical region, which can be explained by different water masses and plankton community structures. In addition, we observed a lithogenic input signal of REEs from the Aleutian Islands based on the high La/Yb ratio (>0.35). This ratio was controlled by lateral transport and showed a good agreement with salinity, indicating that it is a useful tracer of low salinity water originating from the subarctic region. Furthermore, we estimated the cross-shelf fluxes of Nd in the Northwest Pacific. The estimated Nd fluxes from the Sea of Okhotsk, the Sea of Japan, the East China Sea, and the South China Sea into the Northwest Pacific were 29~32 t/y, 159~302 t/y, 142~616 t/y, and -298~34 t/y, respectively. This study highlights the importance of considering the cross-shelf REE fluxes in the Northwest Pacific when constructing the oceanic REE budgets.
Fucosylated TLR4 mediates communication between mutualist fucotrophic microbiota and mammalian gut mucosa
Authors: Nanthakumar Nanda N. , Meng Di , Newburg David S.
Published: March 2023

Objective

The glycans on the mucosa of suckling mice are predominantly sialylated; upon weaning, fucosylated glycans preponderate. This manifestation of mutualism between fucotrophic bacteria and the mature host utilizes a sentinel receptor in the intestinal mucosa; this receptor was isolated to distinguish its structural and functional features.

Design

Provisional identification of the sentinel gut receptor as fuc-TLR4 was through colonization of germ-free mutant mice. Conventional mice whose microbiota was depleted with a cocktail of antibiotics were used to further define the nature and functions of fuc-TLR4 sentinel, and to define the role of the fucotrophic microbiota in gut homeostasis and recovery from insult. The nature of the sentinel was confirmed in cultured human HEL cells.

Results

Fuc-TLR4 activity is distinct from that of TLR4. Activated mucosal fuc-TLR4 induces a fuc-TLR4 dependent non-inflammatory (ERK and JNK dependent, NF-κB independent) signaling cascade, initiating induction of fucosyltransferase 2 (secretor) gene transcription. In vitro, either defucosylation or TLR4 knockdown abrogates FUT2 induction, indicating that fuc-TLR4 activity requires both the peptide and glycan moieties. In vivo, fucose-utilizing bacteria and fucose-binding ligands induce mucosal fucosylation. Activation of this pathway is essential for recovery from chemically induced mucosal injury in vivo.

Conclusion

In mature mice, fucosyl-TLR4 mediated gut fucosylation creates a niche that supports the healthy fucose-dependent mutualism between the mammalian gut and its fucotrophic microbes. Such microbiota-induced Fuc-TLR4 signaling supports initial colonization of the secretor gut, recovery from dysbiosis, and restoration or preservation of intestinal homeostasis.