Bioinformatics and functional analysis of EDS1 genes in Brassica napus in response to Plasmodiophora brassicae infection.

Enhanced Disease Susceptibility 1 (EDS1) is a key regulator of plant-pathogen-associated molecular pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) responses. In the Brassica napus genome, we identified six novel EDS1 genes, among which four were responsive to clubroot infection, a major rapeseed disease resistant to chemical control. Developing resistant cultivars is a potent and economically viable strategy to control clubroot infection. Bioinformatics analysis revealed conserved domains and structural uniformity in Bna-EDS1 homologs. Bna-EDS1 promoters harbored elements associated with diverse phytohormones and stress responses, highlighting their crucial roles in plant defense. A functional analysis was performed with Bna-EDS1 overexpression and RNAi transgenic lines. Bna-EDS1 overexpression boosted resistance to clubroot and upregulated defense-associated genes (PR1, PR2, ICS1, and CBP60), while Bna-EDS1 RNAi increased plant susceptibility, indicating suppression of the defense signaling pathway downstream of NBS-LRRs. RNA-Seq analysis identified key transcripts associated with clubroot resistance, including phenylpropanoid biosynthesis. Activation of SA regulator NPR1, defense signaling markers PR1 and PR2, and upregulation of MYC-TFs suggested that EDS1-mediated clubroot resistance potentially involves the SA pathway. Our findings underscore the pivotal role of Bna-EDS1-dependent mechanisms in resistance of B. napus to clubroot disease, and provide valuable insights for fortifying resistance against Plasmodiophora brassicae infection in rapeseed.

Autism spectrum disorders in boys at a major UK hemophilia center: prevalence and risk factors.

Background: Autism spectrum disorders (ASDs) are diagnosed by social communication difficulties strong, narrow interests, and repetitive stereotyped behavior. An apparently-elevated prevalence of ASD at a major UK hemophilia center warranted investigation. Objectives: To screen boys with hemophilia for difficulties in social communication and executive function and identify the prevalence and risk factors for ASD. Methods: Parents of boys with hemophilia aged 5 to 16 years completed the Social Communication Questionnaire, Children's Communication Checklist, and the Behavior Rating Inventory of executive function. Prevalence and potential risk factors for ASD were evaluated. Boys with an existing diagnosis of ASD did not complete questionnaires, but were included in the prevalence analysis. Results: Negative scores on all 3 questionnaires were observed for 60 of 79 boys. Positive scores on 1, 2, and 3 questionnaires were seen in 12 of 79, 3 of 79, and 4 of 79 boys, respectively. In addition to the 11 of 214 boys with a prior ASD diagnosis, 3 further boys were diagnosed with ASD, yielding a prevalence of 14 (6.5%) of 214, greater than that of boys in the UK general population. Premature birth was linked to having ASD, but did not fully explain the increased prevalence with more boys born <37 weeks scoring positively on the Social Communications Questionnaire and Children's Communication Checklist compared with those born at term. Conclusion: This study identified an increased prevalence of ASD at 1 UK hemophilia center. Prematurity was identified as a risk factor but did not fully explain the higher prevalence of ASD. Further investigation in the wider national/global hemophilia communities is warranted to determine whether this is an isolated finding.

Real-World Data on the Effectiveness and Safety of wilate for the Treatment of von Willebrand Disease.

Background The efficacy and safety of wilate (human von Willebrand factor/coagulation factor VIII) in patients with von Willebrand disease (VWD) has been demonstrated in clinical trials. Here, we present real-world data on the use of wilate for the routine care of patients with VWD. Objectives The objectives of this observational, prospective, phase 4 study were to evaluate the safety, tolerability, and effectiveness of wilate in on-demand treatment of bleeding episodes (BEs), long-term prophylaxis, and surgical prophylaxis among patients with any type of VWD. Methods Patients were enrolled at 31 study centers in 11 countries and followed for up to 2 years. Safety endpoints included adverse drug reactions (ADRs) and drug tolerability. Effectiveness was assessed using annualized bleeding rates (ABRs) during prophylaxis and predefined criteria for the treatment of BEs and surgical prophylaxis. Results A total of 111 patients (76 [68%] female) including 41 (37%) children were treated with wilate. Twenty-five patients received prophylaxis, 29 on-demand treatment, and 62 surgical prophylaxis. Tolerability was rated by patients as "excellent" for 96.2% of 6,497 infusions. No unexpected ADRs or thrombotic events were reported. Median ABR during prophylaxis was 1.9. Effectiveness was assessed as "excellent" or "good" by patients and investigators for 100% of BEs treated on-demand, 98% (patient rating) and 99% (investigator rating) of breakthrough BEs, and 99% of surgical procedures (investigator rating). Conclusion wilate was safe, well tolerated, and effective for the prevention and treatment of bleeding in pediatric and adult VWD patients in a real-world setting.