Evaluating Mechanisms of RNA Editing in Plants

RNA editing is one of several post-transcriptional RNA processes. This process generates RNA and protein diversity in eukaryotes and results in specific amino acid substitutions, deletions, and changes in gene expression levels. It occurs in both plastids and mitochondria and typically involves the changing of specific C to U (cytosine to uracil). Welwitschia belongs to the gymnosperms (a group of seed-producing plants that includes conifers, cycads, Ginkgo, and Gnetales). It has already been substantiated that Welwitschia mirabilis has a major loss of cis-spliced introns and unusual trans-splicing introns. Research in the Mower lab has already proven that ancestral gymnosperm has high editing sites, from examining Ginkgo and Cycas. Knowing these high editing sites in other Gymnosperms, a prediction was made in Welwitschia mirabilis for a major loss of editing. In this study, we wished to evaluate the accuracy of this prediction. Data confirmed that RNA editing is very low in Welwitschia, and surprisingly, even lower than the predicted number. Within the 16 examined functional protein-coding genes in Welwitschia mitogenome, RNA editing sites were detected from only 5 of them

{SoK}: {An} Analysis of Protocol Design: Avoiding Traps for Implementation and Deployment

Today's Internet utilizes a multitude of different protocols. While some of these protocols were first implemented and used and later documented, other were first specified and then implemented. Regardless of how protocols came to be, their definitions can contain traps that lead to insecure implementations or deployments. A classical example is insufficiently strict authentication requirements in a protocol specification. The resulting Misconfigurations, i.e., not enabling strong authentication, are common root causes for Internet security incidents. Indeed, Internet protocols have been commonly designed without security in mind which leads to a multitude of misconfiguration traps. While this is slowly changing, to strict security considerations can have a similarly bad effect. Due to complex implementations and insufficient documentation, security features may remain unused, leaving deployments vulnerable. In this paper we provide a systematization of the security traps found in common Internet protocols. By separating protocols in four classes we identify major factors that lead to common security traps. These insights together with observations about end-user centric usability and security by default are then used to derive recommendations for improving existing and designing new protocols---without such security sensitive traps for operators, implementors and users

{SoK}: {An} Analysis of Protocol Design: Avoiding Traps for Implementation and Deployment

Today's Internet utilizes a multitude of different protocols. While some of these protocols were first implemented and used and later documented, other were first specified and then implemented. Regardless of how protocols came to be, their definitions can contain traps that lead to insecure implementations or deployments. A classical example is insufficiently strict authentication requirements in a protocol specification. The resulting Misconfigurations, i.e., not enabling strong authentication, are common root causes for Internet security incidents. Indeed, Internet protocols have been commonly designed without security in mind which leads to a multitude of misconfiguration traps. While this is slowly changing, to strict security considerations can have a similarly bad effect. Due to complex implementations and insufficient documentation, security features may remain unused, leaving deployments vulnerable. In this paper we provide a systematization of the security traps found in common Internet protocols. By separating protocols in four classes we identify major factors that lead to common security traps. These insights together with observations about end-user centric usability and security by default are then used to derive recommendations for improving existing and designing new protocols---without such security sensitive traps for operators, implementors and users

Prediction of Long-Term Sickness Absence Among Employees with Depressive Complaints

Introduction To study the properties of a screening instrument in predicting long-term sickness absence among employees with depressive complaints. Methods Employees at high risk of future sickness absence were selected by the screening instrument Balansmeter (BM). Depressive complaints were assessed with the depression scale of the Hospital Anxiety and Depression Scale. The total study population consisted of 7,401 employees. Sickness absence was assessed objectively and analyzed at 12 and 18 months of follow-up using company registers on certified sick leave. Results The relative risk (RR) for long-term sickness absence, for employees at high risk versus not at high risk, was 3.26 (95% CI 2.54–4.22) in men and 2.55 (1.98–3.35) in women, when the BM was applied in the total study population. The RR of long-term sickness absence of employees with depressive complaints compared with employees without depressive complaints was 3.13 (2.41–4.09) in men and 2.45 (2.00–3.00) in women. The RR of long-term sickness absence for the BM applied in employees with depressive complaints was 5.23 in men and 3.87 in women. When the BM with a cut-off point with a higher sensitivity was applied in employees with depressive complaints, the RR for long-term sickness absence was 4.88 in men and 3.80 in women. Conclusions The screening instrument Balansmeter is able to predict long-term sickness absence within employees with depressive complaints. The total prediction of long-term sickness absence proved better in employees with depressive complaints compared with employees of a general working population

Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction:A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial

OBJECTIVE:Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST-segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI. METHODS:371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up (clinicaltrial.gov Identifier: NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging. RESULTS:Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001). CONCLUSION:LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size

Leukocyte telomere length and left ventricular function after acute ST-elevation myocardial infarction:data from the glycometabolic intervention as adjunct to primary coronary intervention in ST elevation myocardial infarction (GIPS-III) trial

Background Telomere length has been associated with coronary artery disease and heart failure. We studied whether leukocyte telomere length is associated with left ventricular ejection fraction (LVEF) after ST-elevation myocardial infarction (STEMI). Methods and results Leukocyte telomere length (LTL) was determined using the monochrome multiplex quantitative PCR method in 353 patients participating in the glycometabolic intervention as adjunct to primary percutaneous coronary intervention in STEMI III trial. LVEF was assessed by magnetic resonance imaging. The mean age of patients was 58.9 +/- A 11.6 years, 75 % were male. In age- and gender-adjusted models, LTL at baseline was significantly associated with age (beta +/- A standard error; -0.33 +/- A 0.01; P <0.01), gender (0.15 +/- A 0.03; P <0.01), TIMI flow pre-PCI (0.05 +/- A 0.03; P <0.01), TIMI flow post-PCI (0.03 +/- A 0.04; P <0.01), myocardial blush grade (-0.05 +/- A 0.07; P <0.01), serum glucose levels (-0.11 +/- A 0.01; P = 0.03), and total leukocyte count (-0.11 +/- A 0.01; P = 0.04). At 4 months after STEMI, LVEF was well preserved (54.1 +/- A 8.4 %) and was not associated with baseline LTL (P = 0.95). Baseline LTL was associated with n-terminal pro-brain natriuretic peptide (NT-proBNP) at 4 months (-0.14 +/- A 0.01; P = 0.02), albeit not independent for age and gender. Conclusion Our study does not support a role for LTL as a causal factor related to left ventricular ejection fraction after STEMI

The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction:data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial

Objective: In patients with diabetes mellitus, metformin treatment is associated with reduced mortality and attenuation of cardiovascular risk. As a subanalysis of the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) study, we evaluated whether metformin treatment in patients with ST-segment elevation myocardial infarction (STEMI) without diabetes improves the cardiovascular risk profile. Methods: A total of 379 patients, without known diabetes, presenting with STEMI were randomly allocated to receive metformin 500 mg twice daily or placebo for 4 months. Results: After 4 months, the cardiovascular risk profile of patients receiving metformin (n= 172) was improved compared with placebo (n= 174); glycated hemoglobin (5.83% (95% CI 5.79% to 5.87%) vs 5.89% (95% CI 5.85% to 5.92%); 40.2 mmol/mol (95% CI 39.8 to 40.6) vs 40.9 mmol/mol (40.4 to 41.2), p= 0.049); total cholesterol (3.85 mmol/L (95% CI 3.73 to 3.97) vs 4.02 mmol/L (95% CI 3.90 to 4.14), p= 0.045); low-density lipoprotein cholesterol (2.10 mmol/L (95% CI 1.99 to 2.20) vs 2.3 mmol/L (95% CI 2.20 to 2.40), p= 0.007); body weight (83.8 kg (95% CI 83.0 to 84.7) vs 85.2 kg (95% CI 84.4 to 86.1), p= 0.024); body mass index (26.8 kg/m(2) (95% CI 26.5 to 27.0) vs 27.2 kg/m(2) (95% CI 27.0 to 27.5), p= 0.014). Levels of fasting glucose, postchallenge glucose, insulin, high-density lipoprotein cholesterol, and blood pressure were similar in both groups. Conclusions: Among patients with STEMI without diabetes, treatment with metformin for 4 months resulted in a modest improvement of the cardiovascular risk profile compared with placebo

Predictors of left ventricular remodeling after ST-elevation myocardial infarction

Adverse left ventricular (LV) remodeling after acute ST-elevation myocardial infarction (STEMI) is associated with morbidity and mortality. We studied clinical, biochemical and angiographic determinants of LV end diastolic volume index (LVEDVi), end systolic volume index (LVESVi) and mass index (LVMi) as global LV remodeling parameters 4 months after STEMI, as well as end diastolic wall thickness (EDWT) and end systolic wall thickness (ESWT) of the non-infarcted myocardium, as compensatory remote LV remodeling parameters. Data was collected in 271 patients participating in the GIPS-III trial, presenting with a first STEMI. Laboratory measures were collected at baseline, 2 weeks, and 6-8 weeks. Cardiovascular magnetic resonance imaging (CMR) was performed 4 months after STEMI. Linear regression analyses were performed to determine predictors. At baseline, patients were 21% female, median age was 58 years. At 4 months, mean LV ejection fraction (LVEF) was 54 +/- 9%, mean infarct size was 9.0 +/- 7.9% of LVM. Strongest univariate predictors (all p <0.001) were peak Troponin T for LVEDVi (R-2 = 0.26), peak CK-MB for LVESVi (R-2 = 0.41), NT-proBNP at 2 weeks for LVMi (R-2 = 0.24), body surface area for EDWT (R-2 = 0.32), and weight for ESWT (R-2 = 0.29). After multivariable analysis, cardiac biomarkers remained the strongest predictors of LVMi, LVEDVi and LVESVi. NT-proBNP but none of the acute cardiac injury biomarkers were associated with remote LV wall thickness. Our analyses illustrate the value of cardiac specific biochemical biomarkers in predicting global LV remodeling after STEMI. We found no evidence for a hypertrophic response of the non-infarcted myocardium

Convocation

List of performers and performances