bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic divergence in common bean genotypes from the IRAD gene bank: morpho-agronomic characteristics, fungal and bacterial disease resistance, and opportunities for genetic improvement
Authors: Kouam Eric Bertrand , Djeugap-Fovo Joseph , Meka-Sindje Solange , Afsah Nadia Mokia Mbinkar , Meyia Arielle , Babagnack Blaise Franky , Nouteka Niky K. J. , Galani-Yamdeu Joseph Hubert 
Published: November 2023

For successful plant breeding in any crop species, the importance of diversity in the available germplasm population is known and established. Thirty-two common bean (Phaseolus vulgaris) genotypes from the IRAD gene bank in Cameroon were evaluated for divergence in terms of their morpho-agronomic traits, fungal disease resistance, and bacterial disease resistance to assess the opportunity for genetic improvement of the crop. The trait associations were estimated using correlation coefficients and genotypes were classified into groups using cluster and principal component analyses. Seven qualitative and 16 quantitative traits comprising growth, phenological, yield, and disease variables were evaluated in this study. The qualitative markers revealed the degree of polymorphism among the 32 common bean genotypes. The number of phenotypic classes per character (Na) ranged from 2 to 18, with an average of 5.14. The expected gene diversity (He) ranged from 0.37 to 0.93 (mean = 0.56). The number of effective phenotypic classes (Ne) ranged from 1.82 to 14.22, with a mean of 3.85. An extensive range of variation was evident for the majority of traits, highlighting their utility for characterizing common bean germplasm. Many qualitative traits, including seed coat color, seed shape, and seed size, and also some quantitative traits of economic importance including seed yield, were found to be highly variable within the collection, with the MAC55 genotype displaying the highest yield (32.65 g per plant). Four genotypes, namely MAC55, BOA-5-1M6, FEB 192, and Banguem showed resistance to the two main common bean diseases, angular leaf spot and common blight. We detected highly significant correlations among several traits related to yield. A high broad-sense heritability was found for most of the quantitative traits. We carried out two-dimensional principal component analysis and used hierarchical clustering to group the analyzed germplasm according to their phenotypic similitudes. The evidence of agro-morphological diversity in the present collection and the identification of discriminant characters between the available germplasm through the use of PCA analysis have significant implications for establishing breeding schemes in common bean.
Macrophage IL-1β-positive microvesicles exhibit thrombo-inflammatory properties and are detectable in patients with active juvenile idiopathic arthritis
Authors: Cambon Audrey , Rebelle Charlotte , Bachelier Richard , Arnaud Laurent , Robert Stéphane , Lagarde Marie , Muller Romain , Tellier Edwige , Kara Yéter , Leroyer Aurélie , Farnarier Catherine , Vallier Loris , Chareyre Corinne , Retornaz Karine , Jurquet Anne-Laure , Tran Tu-Anh , Lacroix Romaric , Dignat-George Françoise , Kaplanski Gilles 
Published: November 2023

ObjectiveIL-1β is a leaderless cytokine with poorly known secretory mechanisms that is barely detectable in serum of patients, including those with an IL-1β-mediated disease such as systemic juvenile idiopathic arthritis (sJIA). Leukocyte microvesicles (MVs) may be a mechanism of IL-1β secretion. The first objective of our study was to characterize IL-1β-positive MVs obtained from macrophage cell culture supernatants and to investigate their biological functions in vitro and in vivo. The second objective was to detect circulating IL-1β-positive MVs in JIA patients.MethodsMVs were purified by serial centrifugations from PBMCs, or THP-1 differentiated into macrophages, then stimulated with LPS ± ATP. MV content was analyzed for the presence of IL-1β, NLRP3 inflammasome, caspase-1, P2X7 receptor, and tissue factor (TF) using ELISA, Western blot, or flow cytometry. MV biological properties were studied in vitro by measuring VCAM-1, ICAM-1, and E-selectin expression after HUVEC co-culture and factor-Xa generation test was realized. In vivo, MVs’ ability to recruit leukocytes in a murine model of peritonitis was evaluated. Plasmatic IL-1β-positive MVs were studied ex vivo in 10 active JIA patients using flow cytometry.ResultsTHP-1-derived macrophages stimulated with LPS and ATP released MVs, which contained NLRP3, caspase-1, and the 33-kDa precursor and 17-kDa mature forms of IL-1β and bioactive TF. IL-1β-positive MVs expressed P2X7 receptor and released soluble IL-1β in response to ATP stimulation in vitro. In mice, MVs induced a leukocyte peritoneal infiltrate, which was reduced by treatment with the IL-1 receptor antagonist. Finally, IL-1β-positive MVs were detectable in plasma from 10 active JIA patients.ConclusionMVs shed from activated macrophages contain IL-1β, NLRP3 inflammasome components, and TF, and constitute thrombo-inflammatory vectors that can be detected in the plasma from active JIA patients.
Environmental bisphenol A exposure triggers trained immunity-related pathways in monocytes
Authors: Dallio Marcello , Ventriglia Lorenzo , Romeo Mario , Scognamiglio Flavia , Diano Nadia , Moggio Martina , Cipullo Marina , Coppola Annachiara , Ziogas Athanasios , Netea Mihai G. , Federico Alessandro 
Published: November 2023

IntroductionTrained Immunity represents a novel revolutionary concept of the immunological response involving innate immune cells. Bisphenol A is a well-known endocrine disrupter, widely disseminated worldwide and accumulated in the human body. Due to the increased interest regarding the effects of plastic-derived compounds on the immune system, our purpose was to explore whether BPA was able to induce trained immunity in human primary monocytes in vitro using low environmental concentrations.Materials and methodsWe extracted BPA from the serum of 10 healthy individuals through a liquid-liquid extraction followed by a solid phase extraction and measured the concentration using an HPLC system coupled to a triple quadrupole mass spectrometer. In parallel, monocytes were isolated from whole blood and acutely stimulated or trained with BPA at three different concentrations (1 nM, 10 nM, 20 nM). Pro- and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-10) production were assessed after 24 hours of acute stimulation and after Lipopolysaccharide (LPS) rechallenge. A comprehensive overview of the metabolic changes after BPA acute stimulation and trained immunity induction was assessed through extracellular lactate measurements, Seahorse XFb metabolic flux analysis and ROS production.ResultsMonocytes primed with BPA showed increased pro- and anti-inflammatory cytokine responses upon restimulation, sustained by the modulation of the immunometabolic circuits. Moreover, we proved the non-toxic effect of BPA at each experimental concentration by performing an MTT assay. Additionally, correlation analysis were performed between pro- and anti-inflammatory cytokines production after LPS acute stimulation or BPA-mediated trained immunity and BPA serum concentrations showing a significant association between TNF-α and BPA circulating levels.DiscussionOverall, this study pointed out for the first time the immunological effects of an environmental chemical and plastic-derived compound in the induction of trained immunity in a healthy cohort.
Anti-PD1 does not improve pyroptosis induced by γδ T cells but promotes tumor regression in a pleural mesothelioma mouse model
Authors: Lui Ka Sin , Ye Zuodong , Chan Hoi Ching , Tanaka Yoshimasa , Cheung Allen Ka Loon 
Published: November 2023

IntroductionMesothelioma is an aggressive tumor in the pleural cavity that is difficult to treat. Diagnosis is usually late with minimal treatment options available for the patients and with unfavorable outcomes. However, recent advances in immunotherapy using γδ T cells may have potential against mesothelioma, given its ample tumoricidal and tumor-migratory properties could allow its infiltration to the widespread tumor mass. Thus, we hypothesize that Vδ2 T cells can perform cytotoxic activities against mesothelioma especially when combined with immune checkpoint blocker against PD-1.MethodsHuman Vδ2 T cells were expanded from peripheral blood mononuclear cells using Tetrakis‐pivaloyloxymethyl 2‐(thiazole‐2‐ylamino) ethylidene‐1,1‐bisphosphonate (PTA) plus IL-2 for 13 days, before used to test for cytotoxicity against mesothelioma cell lines. Mesothelioma-bearing mice was established by Intrapleural administration of mesothelioma cell lines to test for the efficacy of Vδ2 T cells plus anti-PD-1 antibody combination treatment. Pyroptosis was evaluated by cell morphology, western blot analysis, and ELISA experiments. Flow cytometry was used to examine expression of BTN2A1, BTN3A1, PD-L1, PD-L2 on mesothelioma cell lines. Immunofluorescence staining was performed to detect Vδ2 T cells post adoptive transfer and characteristics of pyroptosis in ex vivo mesothelioma tissue sections.ResultsIndeed, our data demonstrated that Vδ2 T cells killing mesothelioma can be enhanced by anti-PD-1 antibody in vitro, especially for high PD-1 expressing cells, and in vivo in the intrapleural mesothelioma mice model established by us. Adoptive transfer of Vδ2 T cells into these mice leads to tumor regression by 30-40% compared to control. Immunofluorescence of the tumor section confirmed infiltration of Vδ2 T cells into the tumor, especially to cells with BTN2A1 expression (a Vδ2 T cell activating molecule) despite PD-L1 co-localization. Interestingly, these cells co-expressed cleaved gasdermin D, suggesting that pyroptosis was induced by Vδ2 T cells. This was verified by Vδ2 T/mesothelioma co-culture experiments demonstrating membrane ballooning morphology, increased cleaved caspase-3 and gasdermin E, and upregulated IL-1β and IL-18.DiscussionVδ2 T cells plus anti-PD1 exhibited cytotoxicity against mesothelioma in vivo. However, we found no advantage for anti-PD-1 against PD-1 high expressing Vδ2 T cells in promoting pyroptosis. Taken together, our work demonstrated that Vδ2 T cells combined with anti-PD-1 antibody can be developed as a potential combination immunotherapy for mesothelioma.
Escherichia coli adhesion protein FimH exacerbates colitis via CD11b+CD103- dendritic cell activation
Authors: Zhang Wei , An Eun-Koung , Kim So-Jung , Park Hae-Bin , Lee Peter C. W. , Jin Jun-O 
Published: November 2023

IntroductionImmune stimulators are used to improve vaccine efficiency; however, they are accompanied by various side effects. In previous studies, we reported that the Escherichia coli adhesion protein, FimH, induces immune activity; however, we did not examine any side effects in colon inflammation.MethodsFimH was administered orally or intraperitoneally (i.p.) to mice with dextran sulfate sodium (DSS)-induced colitis, and changes in symptoms were observed. Immune cells infiltrated into the colon after the induction of colon inflammation were analyzed using a flow cytometer. Changes in Th1 and Th17 cells that induce colitis were analyzed. Further, mesenteric lymph node (mLN) dendritic cells (DCs) activated by FimH were identified and isolated to examine their ability to induce T-cell immunity.ResultsFimH oral and i.p. administration in C57BL/6 mice did not induce inflammation in the colon; however, DSS-induced colitis was exacerbated by oral and i.p. FimH administration. FimH treatment increased immune cell infiltration in the colon compared to that in DSS colitis. Th1 and Th17 cells, which are directly related to colitis, were increased in the colon by FimH; however, FimH did not directly affect the differentiation of these T cells. FimH upregulated the CD11b+CD103- DC activity in the mLNs, which produced the signature cytokines required for Th1 and Th17. In addition, isolated CD11b+CD103- DCs, after stimulation with FimH, directly induced Th1 and Th17 differentiation in a co-culture of CD4 T cells.ConclusionThis study demonstrated the side effects of FimH and indicated that the use of FimH can aggravate the disease in patients with colitis.
HLA diversity in ethnic populations can affect detection of donor-specific antibodies by single antigen beads
Authors: Quon Justin C. , Kaneta Kelli , Fotiadis Nicholas , Menteer Jondavid , Lestz Rachel M. , Weisert Molly , Baxter-Lowe Lee Ann 
Published: November 2023

IntroductionIn solid-organ transplantation, human leukocyte antigen (HLA) donor-specific antibodies (DSA) are strongly associated with graft rejection, graft loss, and patient death. The predominant tests used for detecting HLA DSA before and after solid-organ transplantation are HLA single antigen bead (SAB) assays. However, SAB assays may not detect antibodies directed against HLA epitopes that are not represented in the SAB. The prevalence and potential impact of unrepresented HLA epitopes are expected to vary by ethnicity, but have not been thoroughly investigated. To address this knowledge gap, HLA allele frequencies from seven ethnic populations were compared with HLA proteins present in SAB products from two manufacturers to determine unrepresented HLA proteins.MaterialsAllele frequencies were obtained from the Common, Intermediate, and Well Documented HLA catalog v3.0, and frequencies of unrepresented HLA types were calculated. Next-generation sequencing was used to determine HLA types of 60 deceased solid-organ donors, and results were used to determine if their HLA-A, -B, -C, and -DRB1 proteins were not present in SAB reagents from two vendors. Unrepresented HLA proteins were compared with the most similar protein in SAB assays from either vendor and then visualized using modeling software to assess potential HLA epitopes.ResultsFor the seven ethnic populations, 0.5% to 11.8% of each population had HLA proteins not included in SAB assays from one vendor. Non-European populations had greater numbers of unrepresented alleles. Among the deceased donors, 26.7% (16/60) had at least one unrepresented HLA-A, -B, -C, or -DRB1 protein. Structural modeling demonstrated that a subset of these had potential HLA epitopes that are solvent accessible amino acid mismatches and are likely to be accessible to B cell receptors.DiscussionIn conclusion, SAB assays cannot completely rule out the presence of HLA DSA. HLA epitopes not represented in those assays vary by ethnicity and should not be overlooked, especially in non-European populations. Allele-level HLA typing can help determine the potential for HLA antibodies that could evade detection.
Herpes zoster in lupus nephritis: experience on 292 patients followed up for 15 years
Authors: Reggiani Francesco , Cardi Silvia , Tumminello Fabio , Calatroni Marta , Locatelli Laura , Gerosa Maria , Del Papa Nicoletta , Moroni Gabriella 
Published: November 2023

ObjectivesTo evaluate the prevalence, incidence, and predictors of herpes zoster (HZ) development in lupus nephritis (LN).MethodsThis retrospective study included 292 LN patients to determine HZ incidence during the last decades and its correlation with LN activity. LN patients with HZ were matched with LN patients without HZ in a 1:2 ratio based on sex, age, year of LN diagnosis, and LN histological class at kidney biopsy to assess HZ risk factors. Statistical tests included t-test, U-test, and Fisher’s test. Univariate and multivariate logistic regression analyses were conducted to identify potential risk factors.ResultsHZ occurred after LN diagnosis in 66 patients (prevalence 22.6%) with an average of 8.7 years (range 0.2–28.4 years). Although with the potential limitations of the retrospective nature and the extensive duration of the study, the incidence of HZ was 15.6/1,000 person-years, increasing from 6.9 before 1980 to 16.0 in the 1990s and 43.9 after 2010. HZ onset was unrelated to LN activity. LN was active in 43% of cases and quiescent in the other 57% of cases at HZ diagnosis. The percentage of patients who developed lupus flares during the year after HZ (18.9%) was not different from that which occurred during the year before HZ (17.2%, p = 0.804). After excluding confounding factors through matching, the univariate analysis suggested that cyclosporin during induction therapy (p = 0.011) and higher cumulative doses of glucocorticoids (GCs; &gt;50 g, p = 0.004), cyclophosphamide (CYC; &gt;5 g, p = 0.001), and mycophenolate mofetil (MMF &gt; 1,000 g, p = 0.007) predisposed patients to HZ. Univariate and multivariate analyses revealed a protective role of azathioprine (p = 0.008) and methylprednisolone pulses (p = 0.010) during induction therapy.ConclusionsHZ occurs unpredictably throughout the course of LN, underscoring the importance of continuous monitoring for these patients. In addition, the incidence of HZ seems to have increased in recent decades. Induction therapy with azathioprine and methylprednisolone pulses appears to provide protection, while higher cumulative doses of GCs, CYC, and MMF increase susceptibility.
FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma
Authors: Cai Zhenguo , Duan Yanjuan , Li Wen , Liu Zhuohang , Gong Zijun , Hong Sheng , He Xu , Xuanyuan Xinyang , Chen Youdong , Bi Xinling , Wang Wuqing 
Published: November 2023

BackgroundAs a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people’s health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM.MethodsThis study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package “limma” or “DESeq2” in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms.ResultsThe FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy.ConclusionsThe increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.
Single-cell sequencing analysis related to sphingolipid metabolism guides immunotherapy and prognosis of skin cutaneous melanoma
Authors: Ding Yantao , Zhao Zhijie , Cai Huabao , Zhou Yi , Chen He , Bai Yun , Liu Zhenran , Liu Shengxiu , Zhou Wenming 
Published: November 2023

BackgroundWe explore sphingolipid-related genes (SRGs) in skin melanoma (SKCM) to develop a prognostic indicator for patient outcomes. Dysregulated lipid metabolism is linked to aggressive behavior in various cancers, including SKCM. However, the exact role and mechanism of sphingolipid metabolism in melanoma remain partially understood.MethodsWe integrated scRNA-seq data from melanoma patients sourced from the GEO database. Through the utilization of the Seurat R package, we successfully identified distinct gene clusters associated with patient survival in the scRNA-seq data. Key prognostic genes were identified through single-factor Cox analysis and used to develop a prognostic model using LASSO and stepwise regression algorithms. Additionally, we evaluated the predictive potential of these genes within the immune microenvironment and their relevance to immunotherapy. Finally, we validated the functional significance of the high-risk gene IRX3 through in vitro experiments.ResultsAnalysis of scRNA-seq data identified distinct expression patterns of 4 specific genes (SRGs) in diverse cell subpopulations. Re-clustering cells based on increased SRG expression revealed 7 subgroups with significant prognostic implications. Using marker genes, lasso, and Cox regression, we selected 11 genes to construct a risk signature. This signature demonstrated a strong correlation with immune cell infiltration and stromal scores, highlighting its relevance in the tumor microenvironment. Functional studies involving IRX3 knockdown in A375 and WM-115 cells showed significant reductions in cell viability, proliferation, and invasiveness.ConclusionSRG-based risk signature holds promise for precise melanoma prognosis. An in-depth exploration of SRG characteristics offers insights into immunotherapy response. Therapeutic targeting of the IRX3 gene may benefit melanoma patients.
Quantification of the extremely intensified East Korea Warm Current in the summer of 2021: offshore and coastal variabilities
Authors: Pak Gyundo , Lee Kyung-Jae , Lee Seung-Woo , Jin Hyunkeun , Park Jae-Hyoung 
Published: November 2023

In this study, we investigate the record-breaking intensification and abrupt weakening of the East Korea Warm Current (EKWC) in the summer of 2021. We analyzed the ocean data assimilation products resolving this event to examine the association between the abrupt changes in the EKWC and various oceanic/atmospheric factors. The results indicate that during the summer of 2021, the EKWC extended northward beyond its climatology, reaching up to 40°N with the maximum speed of 1.16 m s-1 on August 1. In mid-August, the EKWC underwent a rapid weakening, returning to its climatological level. We could attribute the temporal variability in the anomalous EKWC in 2021 to the distinct temporal variability in the dynamic height anomalies between coastal and offshore regions. The offshore variability in the dynamic height anomaly, which is related to warm eddy variability, led to an anomalously increased EKWC velocity (up to 0.59 m s-1) during the EKWC peak velocity period in 2021. However, anomalous coastal downwelling induced by a weak northerly wind anomaly decelerated the EKWC by -0.06 m s-1 in the same period. In mid-August, a typhoon-related northerly wind induced a sudden rise in the coastal dynamic height anomaly, resulting in a rapid weakening of the EKWC. Our findings suggest that changes in geostrophic current related to warm eddies and typhoons have substantially contributed to the temporal variability in the EKWC, improving our understanding of the temporal variability in the western boundary currents.