Identification of Loci Governing Agronomic Traits and Mutation Hotspots via a GBS-Based Genome-Wide Association Study in a Soybean Mutant Diversity Pool.

In this study, we performed a genotyping-by-sequencing analysis and a genome-wide association study of a soybean mutant diversity pool previously constructed by gamma irradiation. A GWAS was conducted to detect significant associations between 37,249 SNPs, 11 agronomic traits, and 6 phytochemical traits. In the merged data set, 66 SNPs on 13 chromosomes were highly associated (FDR p < 0.05) with the following 4 agronomic traits: days of flowering (33 SNPs), flower color (16 SNPs), node number (6 SNPs), and seed coat color (11 SNPs). These results are consistent with the findings of earlier studies on other genetic features (e.g., natural accessions and recombinant inbred lines). Therefore, our observations suggest that the genomic changes in the mutants generated by gamma irradiation occurred at the same loci as the mutations in the natural soybean population. These findings are indicative of the existence of mutation hotspots, or the acceleration of genome evolution in response to high doses of radiation. Moreover, this study demonstrated that the integration of GBS and GWAS to investigate a mutant population derived from gamma irradiation is suitable for dissecting the molecular basis of complex traits in soybeans.

Epitopes of Protein Binders Are Related to the Structural Flexibility of a Target Protein Surface.

Protein binders including antibodies are known not to bind to random sites of target proteins, and their functional effectiveness mainly depends on the binding region, called the epitope. For the development of protein binders with desired functions, it is thus critical to understand which surface region protein binders prefer (or do not prefer) to bind. The current methods for epitope prediction focus on static indicators such as structural geometry or amino acid propensity, whereas protein binding events are in fact a consequence of dynamic interactions. Here, we demonstrate that the preference for a binding site by protein binders is strongly related to the structural flexibility of a target protein surface. Molecular dynamics simulations on unbound forms of antigen structures revealed that the antigen surface in direct contact with antibodies is less flexible than the rest of the surface. This tendency was shown to be similar in other non-antibody protein binders such as affibody, DARPin, monobody, and repebody. We also found that the relatedness of epitopes to the structural flexibility of a target protein surface is dependent on the secondary structure elements of paratopes. Monobody and repebody, whose binding sites are composed of ß-strands, distinctively prefer to bind to a relatively more rigid region of a target protein. These observations enabled us to develop a simple epitope prediction method which shows a comparable performance to the commonly used ones.

Analysis of genetic diversity and relationships of Perilla frutescens using novel EST-SSR markers derived from transcriptome between wild-type and mutant Perilla.

BACKGROUND: Perilla frutescens (Lamiaceae) is distributed in East Asia and is classified into var. frutescens and crispa. P. frutescens is multipurpose crop for human health because of a variety of secondary metabolites such as phenolic compound and essential oil. However, a lack of genetic information has hindered the development and utilization of Perilla genotypes. METHODS AND RESULTS: This study was performed to develop expressed sequence tag-simple sequence repeat (EST-SSR) markers from P. frutescens var. crispa (wild type) and Antisperill (a mutant cultivar) and used them to assess the genetic diversity of, and relationships among, 94 P. frutescens genotypes. We obtained 65 Gb of sequence data comprising 632,970 transcripts by de novo RNA-sequencing. Of the 14,780 common SSRs, 102 polymorphic EST-SSRs were selected using in silico polymerase chain reaction (PCR). Overall, successful amplification from 58 EST-SSRs markers revealed remarkable genetic diversity and relationships among 94 P. frutescens genotypes. In total, 268 alleles were identified, with an average of 4.62 alleles per locus (range 2-11 alleles/locus). The average polymorphism information content (PIC) value was 0.50 (range 0.04-0.86). In phylogenetic and population structure analyses, the genotypes formed two major groups: Group I (var. crispa) and Group II (var. frutescens). CONCLUSION: This results suggest that 58 novel EST-SSR markers derived from wild-type cultivar (var. crispa) and its mutant cultivar (Antisperill) have potential uses for population genetics and recombinant inbred line mapping analyses, which will provide comprehensive insights into the genetic diversity and relationship of P. frutescens.

Blockade of endothelin receptor A enhances the therapeutic efficacy of gemcitabine in pancreatic cancer cells.

Pancreatic adenocarcinoma is currently one of the leading causes of cancer-related death worldwide. The high rate of mortality in pancreatic cancer patients is due to the inability to detect early-stage disease and the disease being highly refractory to therapy. Gemcitabine has been the standard chemotherapy for advanced pancreatic cancer patients for the last two decades. However, gemcitabine resistance develops within a few weeks of treatment, and the associated mechanism remains poorly understood. Therefore, a novel therapeutic strategy is needed to overcome the limited clinical efficacy of gemcitabine in pancreatic adenocarcinoma. In this study, we demonstrated that ET-1/ETAR axis gene expression was upregulated in pancreatic cancer cells after treatment with gemcitabine. Additionally, ETAR expression was significantly higher in tumor tissues than in normal tissues, and patients with high ETAR expression had a notably worse overall survival rate than those with low ETAR expression. Furthermore, our results revealed that bosentan, an ETAR antagonist, enhanced the growth-inhibiting and proapoptotic effects of gemcitabine on pancreatic cancer cells. Thus, our findings indicate that blockade of the ET-1/ETAR axis signaling pathway promotes the antiproliferative effect of gemcitabine on pancreatic cancer. Therefore, combination of ETAR blockade and gemcitabine serves as an effective therapeutic approach to achieve clinical benefits in pancreatic adenocarcinoma patients.

Phenolic Compounds in Extracts of Hibiscus acetosella (Cranberry Hibiscus) and Their Antioxidant and Antibacterial Properties.

Hibiscus species are rich in phenolic compounds and have been traditionally used for improving human health through their bioactive activities. The present study investigated the phenolic compounds of leaf extracts from 18 different H. acetosella accessions and evaluated their biofunctional properties, focusing on antioxidant and antibacterial activity. The most abundant phenolic compound in H. acetosella was caffeic acid, with levels ranging from 14.95 to 42.93 mg/100 g. The antioxidant activity measured by the ABTS assay allowed the accessions to be classified into two groups: a high activity group with red leaf varieties (74.71-84.02%) and a relatively low activity group with green leaf varieties (57.47-65.94%). The antioxidant activity was significantly correlated with TAC (0.933), Dp3-Sam (0.932), Dp3-Glu (0.924), and Cy3-Sam (0.913) contents (p < 0.001). The H. acetosella phenolic extracts exhibited antibacterial activity against two bacteria, with zones of inhibition between 12.00 and 13.67 mm (Staphylococcus aureus), and 10.67 and 13.33 mm (Pseudomonas aeruginosa). All accessions exhibited a basal antibacterial activity level (12 mm) against the Gram-positive S. aureus, with PI500758 and PI500764 exhibiting increased antibacterial activity (13.67 mm), but they exhibited a more dynamic antibacterial activity level against the Gram-negative P. aeruginosa.

Selection of mutants with high linolenic acid contents and characterization of fatty acid desaturase 2 and 3 genes during seed development in soybean (Glycine max).

BACKGROUND: Soybean seeds contain 18-24% lipids, which are made up of 85% polyunsaturated fatty acids. Two of these (linoleic and linolenic acids) comprise essential fatty acids that are not synthesized in humans and animals. Linolenic acid plays a vital role in the maintenance of brain function and is a source of docosahexaenoic acid for retinal and nerve tissue, with its physiological functions being a focus of attention. RESULTS: We developed mutant soybean populations via gamma irradiation of Korean cultivars Danbaek and Daepung and evaluated the linolenic acid content of 78 and 154 M9 mutant progenies. We selected the four mutant lines with the highest linolenic acid contents based on 2 years of investigation of fatty acids. The selected mutant lines had linolenic acid contents that were 33.9% to 67.7% higher than those of the original cultivars and exhibited increased fatty acid desaturase (FAD) gene expression levels during seed development. We also identified nucleotide polymorphisms of FAD genes in the four mutant lines. CONCLUSION: The present study found that linolenic acid content is related to significantly increased expression levels of the FAD3C and FAD3D genes in the endoplasmic reticulum, which was uncovered by radiation mutation breeding of soybean. © 2019 Society of Chemical Industry.

Engineering and cytosolic delivery of a native regulatory protein and its variants for modulation of ERK2 signaling pathway.

The modulation of a cell signaling process using a molecular binder followed by an analysis of the cellular response is crucial for understanding its role in the cellular function and developing pharmaceuticals. Herein, we present the modulation of the ERK2-mediated signaling pathway through the cytosolic delivery of a native regulatory protein for ERK2, that is, PEA-15 (phosphoprotein enriched in astrocytes, 15 kDa), and its engineered variants using a bacterial toxin-based delivery system. Based on biochemical and structural analyses, PEA-15 variants with different phosphorylation sites and a high affinity for ERK2 were designed. Semi-rational approach led to about an 830-fold increase in the binding affinity of PEA-15, resulting in more effective modulation of the ERK2-mediated signaling. Our approach enabled an understanding of the cellular function of the ERK2-mediated signaling process and the effect of PEA-15 phosphorylation on its action as an ERK2 blocker. We demonstrated the utility and potential of our approach by showing an efficient cytosolic delivery of these PEA-15 variants and the effective suppression of cell proliferation through the inhibition of the ERK2 function. The present approach can be used broadly for modulating the cell signaling processes and understanding their roles in cellular function, as well as for the development of therapeutics.

Gender effect on neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G.

BACKGROUND: Neuromyelitis optica spectrum disorder with aquaporin4-immunoglobulin G (NMOSD-AQP4) is an inflammatory disease characterised by a high female predominance. However, the effect of gender in patients with NMOSD-AQP4 has not been fully evaluated. OBJECTIVE: The aim of this study was to determine the effect of gender in clinical manifestations and prognosis of patients with NMOSD-AQP4. METHODS: The demographics, clinical and radiological characteristics, pattern reversal visual evoked potential (VEP) test results, and prognosis of 102 patients (18 males) with NMOSD-AQP4 were assessed. RESULTS: Male patients had a higher age at onset (48.7 vs 41 years, p = 0.037) and less optic neuritis as the onset attack (17% vs 44%, p = 0.026), higher tendency to manifest as isolated myelitis over the follow-up period (67% vs 28%, p = 0.005), fewer optic neuritis attacks per year (0.08 vs 0.27, p < 0.001), and shorter relative P100 latency on VEP testing (97.1% vs 108.3%, p = 0.001). Moreover, male gender was significantly associated with the absence of optic neuritis attacks over the follow-up period independent of their age of onset. CONCLUSION: In NMOSD-AQP4 patients, gender impacts on disease onset age and site of attack. This may be an important clue in identifying NMOSD-AQP4 patients with limited manifestations as well as in predicting their clinical courses.

Is thyrotoxic periodic paralysis a disease caused by muscle membrane dysfunction?

INTRODUCTION: Thyrotoxic periodic paralysis (TPP) is characterized by recurrent episodes of reversible paralysis with hyperthyroidism. It is clinically similar to hypokalemic periodic paralysis (HOPP), which features significant ion-channel dysfunction and reduced muscle fiber conduction velocity (MFCV). However, the muscle membrane function in TPP is not known. METHODS: For 13 patients with TPP and 15 age-matched controls, clinical assessment and serial neurophysiological testing, including nerve conduction, prolonged exercise (PE) testing, and MFCV. were performed. RESULTS: MFCV values were elevated up to 1 year from the paralytic attack in TPP patients. In the group with a positive PE test, MFCV values were higher. There was no significant relationship between MFCV values and either hypokalemia or hyperthyroidism. CONCLUSIONS: Although clinical manifestations in TPP are similar to those observed in HOPP, TPP appears to feature an alternate pathogenic mechanism. Specifically, MFCV values increased rather than decreased. Further studies are needed to support these findings. Muscle Nerve, 2016 Muscle Nerve 56: 780-786, 2017.

Fermented herbal formula KIOM-MA-128 protects against acute colitis induced by dextran sodium sulfate in mice.

BACKGROUND: Colitis is a well-known subtype of inflammatory bowel disease and is caused by diverse factors. Previous research has shown that KIOM-MA elicits anti-inflammatory and anti-allergic effects on various diseases. KIOM-MA-128, our novel herbal formula, was generated from KIOM-MA using probiotics to improve the therapeutic efficacy. We investigated whether KIOM-MA-128 has protective activity in a mouse model of acute colitis induced by dextran sodium sulfate (DSS). METHODS: Colitis was induced by DSS administered to ICR mice in drinking water. KIOM-MA-128 (125 or 250 mg/kg) was orally administered once per day. The body weights of the mice were measured daily, and colonic endoscopies were performed at 5 and 8 days. Colon length as well as histological and cytokine changes were observed at the end of drug administration. RESULTS: KIOM-MA-128 has pharmacological activity in an acute colitis model. KIOM-MA-128 reduced the loss of body weight and disease activity index (DAI) and inhibited the abnormally short colon lengths and the colonic damage in this mouse model of acute colitis. Moreover, KIOM-MA-128 suppressed pro-inflammatory cytokine expression and maintained the integrity of the tight junctions during DSS-induced colitis. CONCLUSION: The results indicated that KIOM-MA-128 protects against DSS-induced colitis in mice and suggested that this formula might be a candidate treatment for inflammatory bowel disease (IBD).

Inhibitory Effects of Multiple-Dose Treatment with Baicalein on the Pharmacokinetics of Ciprofloxacin in Rats.

Ciprofloxacin is used as a treatment for urinary and respiratory tract infections in clinical practice. Baicalein, a major flavonoid present in Scutellaria baicalensis, is a well-known and potent antibacterial compound used in complementary and alternative medicine practices. The present study aimed to clarify the effects of multiple-dose treatment with baicalein on the pharmacokinetics of ciprofloxacin in rats. Following the oral administration of baicalein (20, 40, or 80 mg/kg) for five consecutive days, the rats received an oral administration of ciprofloxacin (20 mg/kg). Blood samples were collected at specific time points, and the plasma concentrations of ciprofloxacin were determined by using high-performance liquid chromatography. To evaluate the mechanisms underlying the interaction between baicalein and ciprofloxacin, a rhodamine 123 accumulation assay was performed in LS-180 cells. A pharmacokinetic study revealed that multiple-dose treatment with baicalein significantly decreased the peak serum concentration (Cmax ), area under the curve (AUC0 → 480 min ), and relative bioavailability (Frel ) of ciprofloxacin (p < 0.05). The rhodamine 123 accumulation assay revealed that treatment with baicalein for 48 h markedly reduced the intracellular accumulation of rhodamine 123. Taken together, these findings suggest that baicalein may result in the therapeutic failure of ciprofloxacin or other quinolone-based antibiotics used for chemotherapy in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

Split-hand phenomenon in amyotrophic lateral sclerosis: A motor unit number index study.

INTRODUCTION: The split-hand phenomenon refers to preferential wasting of the thenar muscles with relative sparing of the hypothenar muscles in amyotrophic lateral sclerosis (ALS). METHODS: We compared the split-hand index (SI) calculated from the compound muscle action potential (CMAP; SICMAP ) with that calculated from the motor unit number index (MUNIX; SIMUNIX ). We performed MUNIX on the abductor policis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM) muscles of 39 ALS patients and 40 age-matched, healthy controls. SI is derived by multiplying the CMAP (or MUNIX) recorded over the APB and FDI and dividing by the CMAP (or MUNIX) recorded over the ADM. RESULTS: Receiver-operating characteristic curve analysis revealed good diagnostic accuracy for both indices, but better performance of SIMUNIX than SICMAP . CONCLUSION: SIMUNIX and SICMAP were useful in differentiating ALS patients from healthy controls. SIMUNIX appears to be a better electrophysiological marker than SICMAP for the split-hand sign of ALS. Muscle Nerve 53: 885-888, 2016.

Fermented Herbal Formulas KIOM-MA128 Ameliorate IL-6-Induced Intestinal Barrier Dysfunction in Colon Cancer Cell Line.

Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD increases the risk of colorectal cancer (CRC), depending on the extent and duration of intestinal inflammation. Increased IL-6 expression has been reported in IBD patients, which may be associated with intestinal barrier function through discontinuous tight junction (TJ). KIOM-MA is a specific agent for allergic diseases and cancer, and it is composed of several plants; these herbs have been used in traditional oriental medicine. We fermented KIOM-MA, the product of KIOM-MA128, using probiotics to improve the therapeutic efficacy via the absorption and bioavailability of the active ingredients. In this study, we demonstrated that KIOM-MA/MA128 exhibited anticolitis effects via the modulation of TJ protein. Interleukin-6 resulted in a dose-dependent decrease in the TER and an increase in the FITC-dextran permeability; however, pretreatment with 400 µg/ml KIOM-MA/MA128 resulted in a significant increase in the TER and a decrease in the FITC-dextran permeability via IL-6 induction. Furthermore, protein and mRNA TJ levels remained stable after pretreatment with 400 µg/ml KIOM-MA/MA128. Moreover, KIOM-MA/MA128 suppressed the expression of PLCγ1 and PKC. Taken together, these findings suggest novel information and clue of the anticolitis effects of KIOM-MA128 via regulation of tight junction.

The Herbal Medicine KIOM-MA128 Inhibits the Antigen/IgE-Mediated Allergic Response in Vitro and in Vivo.

KIOM-MA128, a novel herbal medicine, has been reported to exert some beneficial effects on various biological events, such as atopic dermatitis, inflammation and cancer. The aim of this study is to investigate how KIOM-MA128 regulates the allergic response. We measured the activity of ß-hexosaminidase and the levels of allergic mediators in the conditioned media of antigen/IgE (Ag/IgE)-activated RBL-2H3 mast cells. We examined the levels of proteins associated with both the FcεRI and arachidonate cascades. Finally, we established the passive cutaneous anaphylaxis (PCA) model in mice to confirm the anti-allergic effects of KIOM-MA128 in vivo. KIOM-MA128 dose-dependently inhibited degranulation and the production of the allergic mediators described above, with no significant cytotoxicity. In the arachidonate cascade, KIOM-MA128 significantly reduced both cytosolic phospholipase A2 (cPLA2) phosphorylation and cyclooxygenase-2 (COX-2) expression. Moreover, in the FcεRI cascade, KIOM-MA128 not only inhibited activation of LYN, FYN and SYK, known as the rate-limiting proteins of the FcεRI cascade, but also suppressed the phosphorylation of ERK, p38 and JNK, which is related to cytokine expression. Finally, 50 to 100 mg/kg KIOM-MA128 significantly attenuated the Ag/IgE-induced PCA reaction in mice. These findings provide novel information and improve our understanding of the anti-allergic effects of KIOM-MA128 on allergic diseases.

Motor unit number index (MUNIX) in the orbicularis oculi muscle of healthy subjects.

INTRODUCTION: The motor unit number index (MUNIX) refers to an electrophysiological method that measures the number of motor units in the surface electromyographic interference pattern (SIP) recorded during graded muscle contractions. MUNIX studies of limb muscles have been conducted, but MUNIX studies of bulbo-facial muscles have not been reported. METHODS: We assessed bilateral orbicularis oculi muscles using MUNIX, and the reference values and reproducibility of MUNIX and motor unit size index (MUSIX) were investigated in healthy subjects. RESULTS: In this study, MUNIX was applied successfully to the orbicularis oculi muscles and showed good reproducibility. The correlation coefficients for MUNIX and MUSIX were 0.803 and 0.592, respectively, and the coefficients of variation were 20.9% and 8.5%, respectively. CONCLUSIONS: The MUNIX procedure for the orbicularis oculi muscle would be a useful tool for evaluating bulbar symptoms, especially in amyotrophic lateral sclerosis.

Fermented soshiho-tang with Lactobacillus plantarum enhances the antiproliferative activity in vascular smooth muscle cell.

BACKGROUND: Soshiho-tang (SST) is a traditional medicine widely used for the treatment of chronic hepatitis. SST has been shown to confer a variety of pharmacological activities, including prevention of hepatotoxicity, promotion of liver regeneration, and modulation of liver fibrosis. In this study, we investigated the antiproliferative activity of native and fermented (FSST) formulations of SST in vascular smooth muscle cells (VSMCs) and examined the potential underlying mechanisms driving these effects. METHODS: SST, along with preparations fermented with Lactobacillus plantarum KFRI-144 (S-A144), L. amylophilus KFRI-161 (S-A161) and L. bulgaricus KFRI-344 (S-A344), were investigated to determine their effects on the proliferation and viability of VSMCs, along with the signalling pathways underlying these effects. RESULTS: S-A144 exhibited a strong, dose-dependent inhibition of VSMC proliferation relative to untreated controls, but the others did not affect. In addition, S-A144 significantly decreased the phosphorylation of Akt and PLCγ1 in a dose-dependent manner and induced cell cycle arrest at the G0/G1 phase characterised by decreased expression of CDKs, cyclins and PCNA. CONCLUSIONS: The findings suggest that S-A144 exhibit enhanced inhibition of PDGF-BB-induced VSMC proliferation comparison to S-AOR through the suppression of cell cycle progression and expression of cell cycle-related proteins, along with the downregulation of Akt phosphorylation.

Assessment of Attractant Combinations for the Management of Red Palm Weevils (Rhynchophorus ferrugineus) in the United Arab Emirates.

This study examined red palm weevil ecology in the United Arab Emirates to develop effective food baits, pheromone, and eco-friendly trapping methods. Three phases of investigation were conducted (from June to December 2023) on date palm farms in Ras Al Khaimah and Abu Dhabi. The first two phases, each 15 days long, were conducted in Ras Al Khaimah, whereas the third phase, 18 days long, was conducted in Abu Dhabi. Chemical attractants, such as existing pheromones and ethyl acetate, a newly synthesized ferruginol pheromone, and food baits, such as original dates, date paste, coconut water, and date palm syrup, were used to attract the weevils. Multi-funnel traps containing various attractant mixes were tested. The main activity of the red palm weevils was observed from 3:00 to 6:00 a.m., with 85.72 ± 3.39% being captured during this period, coinciding with cooler temperatures. When pheromones were added to the food bait, the capture rate increased by 6.95 ± 1.81 times. Combining food bait, ethyl acetate, and pheromones improved the capture rates by 3.14 ± 0.69 times compared to pheromones alone. The newly synthesized pheromone achieved capture rates 2.69 ± 0.07 times higher than those of the commercially available pheromone, confirming its suitability as a red palm weevil attractant.

Instantaneous Thermal Energy for Swift Synthesis of Single-Atom Catalysts for Unparalleled Performance in Metal-Air Batteries and Fuel Cells.

Based on experimental and computational evidence, phthalocyanine (Pc) compounds in the form of quaternary-bound metal-nitrogen (N) atoms are the most effective catalysts for oxygen reduction reaction (ORR). However, the heat treatment process used in their synthesis may compromise the ideal structure, causing the agglomeration of transition metals. To overcome this issue, a novel method is developed for synthesizing iron (Fe) single-atom catalysts with ideal structures supported by thermally exfoliated graphene oxide (GO). This is achieved through a short heat treatment of only 2.5 min involving FePc and N, N-dimethylformamide in the presence of GO. According to the synthesis mechanism revealed by this study, carbon monoxide acts as a strong linker between the single Fe atoms and graphene. It facilitates the formation of a structure containing oxygen species between FeN4 and graphene, which provides high activity and stability for the ORR. These catalysts possess an enormous number of active sites and exhibit enhanced activity toward the alkaline ORR. They demonstrate excellent performance when applied to real electrochemical devices, such as zinc-air batteries and anion exchange membrane fuel cells. It is expected that the instantaneous heat treatment method developed in this study will aid in the development of high-performing single-atom catalysts.

Genotyping-by-Sequencing Analysis Reveals Associations between Agronomic and Oil Traits in Gamma Ray-Derived Mutant Rapeseed (Brassica napus L.).

Rapeseed (Brassica napus L.) holds significant commercial value as one of the leading oil crops, with its agronomic features and oil quality being crucial determinants. In this investigation, 73,226 single nucleotide polymorphisms (SNPs) across 95 rapeseed mutant lines induced by gamma rays, alongside the original cultivar ('Tamra'), using genotyping-by-sequencing (GBS) analysis were examined. This study encompassed gene ontology (GO) analysis and a genomewide association study (GWAS), thereby concentrating on agronomic traits (e.g., plant height, ear length, thousand-seed weight, and seed yield) and oil traits (including fatty acid composition and crude fat content). The GO analysis unveiled a multitude of genes with SNP variations associated with cellular processes, intracellular anatomical structures, and organic cyclic compound binding. Through GWAS, we detected 320 significant SNPs linked to both agronomic (104 SNPs) and oil traits (216 SNPs). Notably, two novel candidate genes, Bna.A05p02350D (SFGH) and Bna.C02p22490D (MDN1), are implicated in thousand-seed weight regulation. Additionally, Bna.C03p14350D (EXO70) and Bna.A09p05630D (PI4Kα1) emerged as novel candidate genes associated with erucic acid and crude fat content, respectively. These findings carry implications for identifying superior genotypes for the development of new cultivars. Association studies offer a cost-effective means of screening mutants and selecting elite rapeseed breeding lines, thereby enhancing the commercial viability of this pivotal oil crop.

TNFα induced noncanonical NF-κB activation is attenuated by RIP1 through stabilization of TRAF2.

The current paradigm of noncanonical NF-κB signaling suggests that the loss of TRAF2, TRAF3 or cIAP1 and cIAP2 leads to stabilization of NF-κB-inducing kinase (NIK) to activate the noncanonical pathway. Although a crucial role of RIP1 in the TNFα-induced canonical NF-κB pathway has been well established, its involvement in noncanonical activation of NF-κB through the TNFR1 receptor, is unknown. Here we show that TNFα is capable of activating the noncanonical NF-κB pathway, but that activation of this pathway is negatively regulated by RIP1. In the absence of RIP1, TNFR1 stimulation leads to activation of the noncanonical NF-κB pathway through TRAF2 degradation, leading to NIK stabilization, IKKα phosphorylation and the processing of p100 to generate p52. Thus although RIP1(-/-) mouse embryonic fibroblasts are sensitive at early time points to cell death induced by TNFα, probably as a result of lack of canonical NF-κB activation, the late activation of the noncanonical NF-κB pathway protects the remaining cells from further cell death. The TNFR1-dependent noncanonical NF-κB activation in RIP1(-/-) cells suggests that there is functional interplay between the two NF-κB pathways during TNFR1 signaling, which might regulate the number and kinds of NF-κB transcription factors and thus finely control NF-κB-dependent gene transcription.