The Lantern Vol. 57, No. 1, Fall 1990

• Candlelight Ecstasy Tabitha • Waffle Maker • Thoughts From the Street Corner • The Grip • Eugenio\u27s Room • Amnesiac • Life at the Edge • College Love • Dry Ice and Red Roses • Forever a Monument • Melanie • Respectable Man • Conversation With Craig • Cheddar Cheese Trees • The Jazz Butcher vs. The Oreos • Sally\u27s Home From Vacation • So She Saidhttps://digitalcommons.ursinus.edu/lantern/1137/thumbnail.jp

The Lantern Vol. 56, No. 2, Spring 1990

• Brasil • Plastic Flowers • Be a Pepper • Grunge • Handling the Responsibility • Returning to the Forest • How Nice • Nooze • Emma • Restoration • Chestnuts • Frozen Moments • Once Upon A • Clipped Wings • Gerard Manley Hopkins • Roaches • In Grand Central • The Steelville Shark • Panama 1989 • Betrayal • Violations • Detourhttps://digitalcommons.ursinus.edu/lantern/1136/thumbnail.jp

Eigenschaften, Häufigkeit und Verbreitung von Vancomycin-resistenten Enterokokken in Deutschland – Update

Vancomycin-resistente Enterokokken (VRE) gehören zu den in Deutschland gemäß § 23 Abs. 4 IfSG zu erfassenden Erregern und werden in vielen deutschen Kliniken häufig beobachtet. Der Nachweis von VRE ist in den zurückliegenden Jahren auf einem stabil hohen Niveau in Deutschland und bewegt sich leicht oberhalb des EU-Durchschnitts. Die Krankheitslast durch invasive VRE-Infektionen ist hingegen nachweislich ansteigend. Das Nationale Referenzzentrum für Staphylokokken und Enterokokken beobachtet diese Entwicklungen und berichtet über die Situation von VRE und Enterokokken mit besonderen Antibiotikaresistenzen im Zeitraum 2021/2022. Darüber hinaus wird auf allgemeine VRE-Resistenzsta¬tistiken nationaler Erhebungssysteme und -studien hingewiesen.Peer Reviewe

Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition

Epigenome-wide association study of incident type 2 diabetes:a meta-analysis of five prospective European cohorts

AIMS/HYPOTHESIS: Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.METHODS: We conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).RESULTS: The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values &lt;1.1 × 10-7). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values &lt;0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA1c) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.CONCLUSIONS/INTERPRETATION: By combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.</p

Common coding variant in SERPINA1 increases the risk for large artery stroke

Large artery atherosclerotic stroke (LAS) shows substantial heritability not explained by previous genome-wide association studies. Here, we explore the role of coding variation in LAS by analyzing variants on the HumanExome BeadChip in a total of 3,127 cases and 9,778 controls from Europe, Australia, and South Asia. We report on a nonsynonymous single-nucleotide variant in serpin family A member 1 (SERPINA1) encoding alpha-1 antitrypsin [AAT; p.V213A; P = 5.99E-9, odds ratio (OR) = 1.22] and confirm histone deacetylase 9 (HDAC9) as a major risk gene for LAS with an association in the 3?-UTR (rs2023938; P = 7.76E-7, OR = 1.28). Using quantitative microscale thermophoresis, we show that M1 (A213) exhibits an almost twofold lower dissociation constant with its primary target human neutrophil elastase (NE) in lipoprotein-containing plasma, but not in lipid-free plasma. Hydrogen/deuterium exchange combined with mass spectrometry further revealed a significant difference in the global flexibility of the two variants. The observed stronger interaction with lipoproteins in plasma and reduced global flexibility of the Val-213 variant most likely improve its local availability and reduce the extent of proteolytic inactivation by other proteases in atherosclerotic plaques. Our results indicate that the interplay between AAT, NE, and lipoprotein particles is modulated by the gate region around position 213 in AAT, far away from the unaltered reactive center loop (357-360). Collectively, our findings point to a functionally relevant balance between lipoproteins, proteases, and AAT in atherosclerosis

Low-frequency variation near common germline susceptibility loci are associated with risk of Ewing sarcoma

Background: Ewing sarcoma (EwS) is a rare, aggressive solid tumor of childhood, adolescence and young adulthood associated with pathognomonic EWSR1-ETS fusion oncoproteins altering transcriptional regulation. Genome-wide association studies (GWAS) have identified 6 common germline susceptibility loci but have not investigated low-frequency inherited variants with minor allele frequencies below 5% due to limited genotyped cases of this rare tumor. Methods We investigated the contribution of rare and low-frequency variation to EwS susceptibility in the largest EwS genome-wide association study to date (733 EwS cases and 1,346 unaffected controls of European ancestry). Results We identified two low-frequency variants, rs112837127 and rs2296730, on chromosome 20 that were associated with EwS risk (OR = 0.186 and 2.038, respectively;P-value < 5x10(-8)) and located near previously reported common susceptibility loci. After adjusting for the most associated common variant at the locus, only rs112837127 remained a statistically significant independent signal (OR = 0.200, P-value = 5.84x10(-8)). Conclusions: These findings suggest rare variation residing on common haplotypes are important contributors to EwS risk. Impact Motivate future targeted sequencing studies for a comprehensive evaluation of low-frequency and rare variation around common EwS susceptibility loci