Combined QTL mapping on bi-parental immortalized heterozygous populations to detect the genetic architecture on heterosis

From bi-parental pure-inbred lines (PIL), immortalized backcross (i.e., IB1 and IB2, representing the two directions of backcrossing) and F2 (i.e., IF2) populations can be developed. These populations are suitable for genetic studies on heterosis, due to the present of both homozygous and heterozygous genotypes, and in the meantime allow repeated phenotyping trials across multiple locations and years. In this study, we developed a combined approach of quantitative trait locus (QTL) mapping, when some or all of the four immortalized populations (i.e., PIL, IB1, IB2, and IF2) are available. To estimate the additive and dominant effects simultaneously and accurately, suitable transformations are made on phenotypic values from different populations. When IB1 and IB2 are present, summation and subtraction are used. When IF2 and PIL are available, mid-parental values and mid-parental heterosis are used. One-dimensional genomic scanning is performed to detect the additive and dominant QTLs, based on the algorithm of inclusive composite interval mapping (ICIM). The proposed approach was applied to one IF2 population together with PIL in maize, and identified ten QTLs on ear length, showing varied degrees of dominance. Simulation studies indicated the proposed approach is similar to or better than individual population mapping by QTL detection power, false discovery rate (FDR), and estimated QTL position and effects

Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells

10.1186/s12906-017-1635-1BMC Complementary and Alternative Medicine17112

Mitochondrial DNA Leakage Caused by Streptococcus pneumoniae Hydrogen Peroxide Promotes Type I IFN Expression in Lung Cells

Streptococcus pneumoniae (S. pn), the bacterial pathogen responsible for invasive pneumococcal diseases, is capable of producing substantial amounts of hydrogen peroxide. However, the impact of S. pn-secreted hydrogen peroxide (H2O2) on the host immune processes is not completely understood. Here, we demonstrated that S. pn-secreted H2O2 caused mitochondrial damage and severe histopathological damage in mouse lung tissue. Additionally, S. pn-secreted H2O2 caused not only oxidative damage to mitochondrial deoxyribonucleic acid (mtDNA), but also a reduction in the mtDNA content in alveolar epithelia cells. This resulted in the release of mtDNA into the cytoplasm, which subsequently induced type I interferons (IFN-I) expression. We also determined that stimulator of interferon genes (STING) signaling was probably involved in S. pn H2O2-inducing IFN-I expression in response to mtDNA damaged by S. pn-secreted H2O2. In conclusion, our study demonstrated that H2O2 produced by S. pn resulted in mtDNA leakage from damaged mitochondria and IFN-I production in alveolar epithelia cells, and STING may be required in this process, and this is a novel mitochondrial damage mechanism by which S. pn potentiates the IFN-I cascade in S. pn infection

Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth Factor-β1-Smad2/3 Pathway

Vaccine effectiveness is mainly determined by the mechanism mediating protection, emphasizing the importance of unraveling the protective mechanism for novel pneumococcal vaccine development. We previously demonstrated that the regulatory T cell (Treg) immune response has a protective effect against pneumococcal infection elicited by the live-attenuated pneumococcal vaccine SPY1. However, the mechanism underlying this protective effect remains unclear. In this study, a short synthetic peptide (P17) was used to downregulate Tregs during immunization and subsequent challenges in a mouse model. In immunized mice, increase in immune cytokines (IL-12p70, IL-4, IL-5, and IL-17A) induced by SPY1 were further upregulated by P17 treatment, whereas the decrease in the infection-associated inflammatory cytokine TNF-α by SPY1 was reversed. P17 also inhibited the increase in the immunosuppressive cytokine IL-10 and inflammatory mediator IL-6 in immunized mice. More severe pulmonary injuries and more dramatic inflammatory responses with worse survival in P17-treated immunized mice indicated the indispensable role of the Treg immune response in protection against pneumococcal infection by maintaining a balance among acquired immune responses stimulated by SPY1. Further studies revealed that the significant elevation of active transforming growth factor β (TGF-β)1 by SPY1 vaccination activated FOXP3, leading to increased frequencies of CD4+CD25+Foxp3+ T cells. Moreover, SPY1 vaccination elevated the levels of Smad2/3 and phosphor-Smad2/3 and downregulated the negative regulatory factor Smad7 in a time-dependent manner during pneumococcal infection, and these changes were reversed by P17 treatment. These results illustrate that SPY1-stimulated TGF-β1 induced the generation of SPY1-specific Tregs via the Smad2/3 signaling pathway. In addition, SPY1-specific Tregs may participate in protection via the enhanced expression of PD-1 and CTLA-4. The data presented here extend our understanding of how the SPY1-induced acquired Treg immune response contributes to protection elicited by live-attenuated vaccines and may be helpful for the evaluation of live vaccines and other mucosal vaccine candidates

High Follicle-Stimulating Hormone Level Associated With Risk of Rheumatoid Arthritis and Disease Activity

BackgroundThe prevalence of rheumatoid arthritis (RA) has significant gender and age difference. The peak age of RA is consistent with the age of menopause, which is accompanied by a sharp increase in serum follicle-stimulating hormone (FSH) level. This study aims to identify the FSH levels in female RA patients and the relationship with diseases activity.MethodsIn total, 79 female RA patients and 50 age-matched controls were included in our study. Serum sex hormones levels were measured using chemiluminescence. RA patients were grouped by FSH quartile. Disease activity and inflammatory marks were analyzed among groups.ResultsLower sex hormones and higher gonadotropin were found in RA patients. Serum FSH level was significantly higher in RA patients than in the age-match controls (57.58 ± 15.94 vs. 43.11 ± 19.46, p=0.025). Even after adjusting for age (OR: 1.071; 95%CI: 1.006-1.139; p = 0.031), luteinizing hormone (LH), estradiol (E), and testosterone (T) OR: 1.066; 95%CI: 1.003-1.133; p = 0.039), the OR were still more than one. RA patients in the higher quartiles had higher ESR, DAS28-ESR and DAS28-CRP (p<0.05) than the lowest quartile. Besides, menopause age was significantly related with onset age in post-menopause RA patients (r = 0.432, p =0.008).ConclusionHigh FSH appears to be a risk factor for RA and is positively associated with their disease activity. Early menopause might be an essential factor of RA

Comparative efficacy of olaparib in combination with or without novel antiandrogens for treating metastatic castration-resistant prostate cancer

BackgroundStudies using novel antiandrogens (NAA) in patients with metastatic castration-resistant prostate cancer (mCRPC) have shown overall survival benefit. As patients develop resistance to NAA therapy, the poly(ADP-ribose) polymerase inhibitor (PARPi) olaparib in combination with NAA may become a promising therapy. However the overall benefit of olaparib monotherapy or combination therapy still needs to be evaluated. Therefore, we performed a network meta-analysis to assess the efficacy and toxicity between olaparib, olaparib combined with abiraterone and NAA.MethodsWe searched PubMed, EMBASE, the Cochrane Library and American Society of Clinical Oncology (ASCO) University Meeting abstracts for randomized controlled trials reporting olaparib and NAA from 2010 up to March, 2023. Network meta-analysis using Stata 16.0 and R 4.4.2, hazard ratios (HR) with 95% confidence intervals (CI) were used to assess the results.ResultsFour trials reported olaparib, olaparib plus abiraterone and apalutamide plus abiraterone. radiographic progression-free survival (rPFS) was significantly lower in patients on apalutamide plus abiraterone compared to olaparib (HR, 1.43; 95% CI, 1.06-1.93). rPFS was similar for olaparib plus abiraterone and olaparib (HR, 1.35; 95% CI, 0.99-1.84); likewise, olaparib plus abiraterone and apalutamide plus abiraterone were similar (HR, 1.06; 95% CI, 0.83-1.35). In addition, there was no significant difference between the three interventions for OS. But olaparib has the highest probability of being a preferred treatment for improving rPFS and OS.ConclusionrPFS was in favor of olaparib compared with apalutamide plus abiraterone. But there were no difference between olaparib plus abiraterone and either olaparib or apalutamide plus abiraterone. Apalutamide plus abiraterone might be the most preferred intervention in cases where AEs are involved.Systematic review registrationhttps://inplasy.com, identifier INPLASY2023100072

Study on Vegetation Classification Based on Spectral Knowledge Base

International audienceA framework about spectral based vegetation classification was proposed, which serves as a core methodology of the vegetation spectral knowledge base. The hyperspectral reflectances of 13 types of plants were measured by an ASD FieldSpec 4 spectroradiometer. Two forms of spectral features were used for representing the key spectral characteristics of plants, including Vegetation index (VI) and spectral shape features. Based on these spectral features, a sensitivity analysis was performed to identify the most important features for establishing the classifier. The analysis of variance (ANOVA) and the cross-correlation analysis were applied to derive the sensitivity of features and remove features that have high correlations. Then, a classification method for differentiating plants was established by coupling some spectral similarity measures (e.g., ED) with some classification methods (e.g., BPANN and SVM). The results of discrimination analysis showed that a highest accuracy was produced by SVM with the OAA over 99% when using 7 sensitive VIs. The results suggested the framework about spectral based vegetation classification can form a basis for spectral knowledge base and application technology and further achieve a wide range of plant classification based on remote sensing

Porcine ZBED6 regulates growth of skeletal muscle and internal organs via multiple targets

ZBED6 (zinc finger BED domain containing protein 6) is a transcription factor unique to placental mammals and its interaction with the IGF2 (insulin-like growth factor 2) locus plays a prominent role in the regulation of postnatal skeletal muscle growth. Here, we generated lean Bama miniature pigs by generating ZBED6-knockout (ZBED6(-/-)) and investigated the mechanism underlying ZBED6 in growth of muscle and internal organs of placental mammals. ZBED6(-/-) pigs show markedly higher lean mass, lean mass rate, larger muscle fiber area and heavier internal organs (heart and liver) than wild-type (WT) pigs. The striking phenotypic changes of ZBED6(-/-) pigs coincided with remarkable upregulation of IGF2 mRNA and protein expression across three tissues (gastrocnemius muscle, longissimus dorsi, heart). Despite a significant increase in liver weight, ZBED6(-/-) pigs show comparable levels of IGF2 expression to those of WT controls. A mechanistic study revealed that elevated methylation in the liver abrogates ZBED6 binding at the IGF2 locus, explaining the unaltered hepatic IGF2 expression in ZBED6(-/-) pigs. These results indicate that a ZBED6-IGF2-independent regulatory pathway exists in the liver. Transcriptome analysis and ChIP-PCR revealed new ZBED6 target genes other than IGF2, including cyclin dependent kinase inhibitor 1A (CDKN1A) and tsukushi, small leucine rich proteoglycan (TSKU), that regulates growth of muscle and liver, respectively. Author summaryThe lean meat rate is an important economic trait for the swine industry and it is determined by muscle growth and development. A single base change in intron 3 of the insulin-like growth factor 2 (IGF2) gene increases meat production in pigs by disrupting a binding site for zinc finger BED domain containing protein 6 (ZBED6). Chinese indigenous pig breeds carrying the homozygous IGF2 wild-type allele produce low lean meat. We thus generate a lean pig model in Chinese Bama pig by knocking out ZBED6. In this model, we demonstrate that ZBED6 KO increases muscle and internal organ growth through ZBED6-IGF2 axis and other target genes. These results not only open new strategies for lean meat breeding in Chinese indigenous pigs, but also provide new insights to the global function of ZBED6 in organ growth and development

Effects of single-side and double-side friction stir processing on microstructure and properties of Mg-Zn-Y-Nd alloy thick plate

In order to obtain a large modified zone with uniform microstructure and good comprehensive properties, single-side and double-side friction stir processings of Mg-Zn-Y-Nd alloy thick plate were carried out, and the microstructure and properties of the processed plates were studied. The results show that the microstructure of the alloy is obviously refined after friction stir processing. The average grain sizes of the upper, mid and lower samples in the stirring zone after single-side and double-side friction stir processings are 4.45 μm, 5.08 μm,5.30 μm and 3.93 μm, 3.20 μm and 3.19 μm respectively. Compared with the homogenizing annealing alloy and single-side friction stir processed alloy, the microstructure of the double-side friction stir processed alloy is more uniform and fine, and the tensile strength and elongation of the lower stirring zone are the highest, 283.3 MPa and 23.9% respectively, and also the corrosion resistance is the best. The corrosion mode is changed from pitting corrosion to uniform corrosion