LCLS accelerator operation and measurement of electron beam parameters relevant for the X-ray beam

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CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection

Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD

Contemporary educational methods in periodontology.

AIM The 1st European Workshop on Periodontal Education in 2009 made recommendations regarding the scope of periodontal education at undergraduate (UG), postgraduate (PG) and continuing professional development (CPD) levels, defining competencies and learning outcomes that were instrumental at the time in helping to define periodontal teaching curricula. The 19th European Workshop on Periodontology and 2nd European Consensus Workshop on Education in Periodontology (Education in Periodontology in Europe) was held in 2023 to identify changes and future developments in periodontal education (including those informed by the COVID-19 pandemic) and embracing methods and formats of periodontal teaching and training. The aim of this review was to assess current knowledge regarding education methods in periodontology, including traditional face-to-face (F2F) teaching and the move to student-centred methods, virtual learning methods and use of digital technology, as well as blended teaching and learning (including teaching delivery and assessment) at UG, PG and CPD levels. MATERIALS AND METHODS Systematic searches were conducted to identify relevant studies from the literature. Data were extracted and descriptive summaries collated. RESULTS The pandemic was a major disruptor of traditional F2F teaching but provided opportunities for rapid implementation of alternative and supplementary teaching methods. Although online learning has become an integral part of periodontal education, teachers and learners alike favour some form of F2F teaching. Blended teaching and learning are feasible in many areas of periodontal education, both for knowledge and skills acquisition as well as in assessment. Student-centred methods and blended approaches such as the flipped classroom seem highly effective, and online/virtual classrooms with both synchronous and asynchronous lectures are highly valued. Learning with haptic methods and virtual reality (VR) enhances the educational experience, especially when VR is integrated with traditional methods. The quality of the teacher continues to be decisive for the best knowledge transfer in all its forms. CONCLUSIONS Live F2F teaching continues to be highly trusted; however, all types of student-centred and interactive forms of knowledge transfer are embraced as enhancements. While digital methods offer innovation in education, blended approaches integrating both virtual and traditional methods appear optimal to maximize the achievement of learning outcomes. All areas of periodontal education (UG, PG and CPD) can benefit from such approaches; however, more research is needed to evaluate their benefits, both for knowledge transfer and skills development, as well as in assessment

Sex‐specific genetic factors affect the risk of early‐onset periodontitis in Europeans

Aims: Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods: Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results: In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions: Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis

A genome-wide association study meta-analysis in a European sample of stage III/IV grade C periodontitis patients ≤35 years of age identifies new risk loci

Aim:Few genome-wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta-analysis in cases with a diagnosis at &lt;= 35 years of age was performed.Materials and Methods:Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age &lt;= 35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data.Results:The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 x 10(-9)), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p &lt; 10(-5), including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 x 10(-8)).Conclusions:This study expands the set of known genetic loci for severe periodontitis with an age of onset &lt;= 35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health

Salinity and host drive Ulva ‐associated bacterial communities across the Atlantic–Baltic Sea gradient

The green seaweed Ulva is a model system to study seaweed–bacteria interactions, but the impact of environmental drivers on the dynamics of these interactions is little understood. In this study, we investigated the stability and variability of the seaweed-associated bacteria across the Atlantic–Baltic Sea salinity gradient. We characterized the bacterial communities of 15 Ulva sensu lato species along 2,000 km of coastline in a total of 481 samples. Our results demonstrate that the Ulva-associated bacterial composition was strongly structured by both salinity and host species (together explaining between 34% and 91% of the variation in the abundance of the different bacterial genera). The largest shift in the bacterial consortia coincided with the horohalinicum (5–8 PSU, known as the transition zone from freshwater to marine conditions). Low-salinity communities especially contained high relative abundances of Luteolibacter, Cyanobium, Pirellula, Lacihabitans and an uncultured Spirosomaceae, whereas high-salinity communities were predominantly enriched in Litorimonas, Leucothrix, Sulfurovum, Algibacter and Dokdonia. We identified a small taxonomic core community (consisting of Paracoccus, Sulfitobacter and an uncultured Rhodobacteraceae), which together contributed to 14% of the reads per sample, on average. Additional core taxa followed a gradient model, as more core taxa were shared between neighbouring salinity ranges than between ranges at opposite ends of the Atlantic–Baltic Sea gradient. Our results contradict earlier statements that Ulva-associated bacterial communities are taxonomically highly variable across individuals and largely stochastically defined. Characteristic bacterial communities associated with distinct salinity regions may therefore facilitate the host's adaptation across the environmental gradient

Translation of mouse model to human gives insights into periodontitis etiology

To suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10-4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10-5) and RNASE2 (rs2771342, P = 2.84×10-5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10-14) and HLA-DPA1 (rs17214512, P = 5.14×10-5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease

CDKN2BAS is associated with periodontitis in different European populations and is activated by bacterial infection

Epidemiological studies have indicated a relationship between coronary heart disease (CHD) and periodontitis. Recently, CDKN2BAS was reported as a shared genetic risk factor of CHD and aggressive periodontitis (AgP), but the causative variant has remained unknown. To identify and validate risk variants in different European populations, we first explored 150 kb of the genetic region of CDKN2BAS including the adjacent genes CDKN2A and CDKN2B, covering 51 tagging single nucleotide polymorphisms (tagSNPs) in AgP and chronic periodontitis (CP) in individuals of Dutch origin (n=313). In a second step, we tested the significant SNP associations in an independent AgP and CP population of German origin (n=1264). For the tagSNPs rs1360590, rs3217992, and rs518394, we could validate the associations with AgP before and after adjustment for the covariates smoking, gender and diabetes, with SNP rs3217992 being the most significant (OR 1.48, 95% CI 1.19 to 1.85; p=0.0004). We further showed in vivo gene expression of CDKN2BAS, CDKN2A, CDKN2B, and CDK4 in healthy and inflamed gingival epithelium (GE) and connective tissue (CT), and detected a significantly higher expression of CDKN2BAS in healthy CT compared to GE (p=0.004). After 24 h of stimulation with Porphyromonas gingivalis in Streptococcus gordonii pre-treated gingival fibroblast (HGF) and cultured gingival epithelial cells (GECs), we observed a 25-fold and fourfold increase of CDKN2BAS gene expression in HGFs (p=0.003) and GECs (p=0.004), respectively. Considering the global importance of CDKN2BAS in the disease risk of CHD, this observation supports the theory of inflammatory components in the disease physiology of CHD

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition