University of Southern Denmark

About: University of Southern Denmark is a education organization based out in Odense, Syddanmark, Denmark. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 11928 authors who have published 37918 publications receiving 1258559 citations. The organization is also known as: SDU.

Improved silencing properties using small internally segmented interfering RNAs

Abstract: RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19-27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10-12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo.

Detection of tyrosine phosphorylated peptides by precursor ion scanning quadrupole TOF mass spectrometry in positive ion mode.

Abstract: Phosphorylation is a common form of protein modification. To understand its biological role, the site of phosphorylation has to be determined. Generally, only limited amounts of phosphorylated proteins are present in a cell, thus demanding highly sensitive procedures for phosphorylation site determination. Here, a novel method is introduced which enables the localization of tyrosine phosphorylation in gel-separated proteins in the femtomol range. The method utilizes the immonium ion of phosphotyrosine at m/z 216.043 for positive ion mode precursor ion scanning combined with the recently introduced Q2-pulsing function on quadrupole TOF mass spectrometers. The high resolving power of the quadrupole TOF instrument enables the selective detection of phosphotyrosine immonium ions without interference from other peptide fragments of the same nominal mass. Performing precursor ion scans in the positive ion mode facilitates sequencing, because there is a no need for polarity switching or changing pH of the sprayi...

A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites

Abstract: Neutrophil NADPH oxidase plays a key role in host defense and in inflammation by releasing large amounts of superoxide and other ROSs. Proinflammatory cytokines such as GM-CSF and TNF-alpha prime ROS production by neutrophils through unknown mechanisms. Here we used peptide sequencing by tandem mass spectrometry to show that GM-CSF and TNF-alpha induce phosphorylation of Ser345 on p47phox, a cytosolic component of NADPH oxidase, in human neutrophils. As Ser345 is located in the MAPK consensus sequence, we tested the effects of MAPK inhibitors. Inhibitors of the ERK1/2 pathway abrogated GM-CSF-induced phosphorylation of Ser345, while p38 MAPK inhibitor abrogated TNF-alpha-induced phosphorylation of Ser345. Transfection of HL-60 cells with a mutated p47phox (S345A) inhibited GM-CSF- and TNF-alpha-induced priming of ROS production. This event was also inhibited in neutrophils by a cell-permeable peptide containing a TAT-p47phox-Ser345 sequence. Furthermore, ROS generation, p47phox-Ser345 phosphorylation, and ERK1/2 and p38 MAPK phosphorylation were increased in synovial neutrophils from rheumatoid arthritis (RA) patients, and TAT-Ser345 peptide inhibited ROS production by these primed neutrophils. This study therefore identifies convergent MAPK pathways on Ser345 that are involved in GM-CSF- and TNF-alpha-induced priming of neutrophils and are activated in RA. Inhibition of the point of convergence of these pathways might serve as a novel antiinflammatory strategy.

Health-related quality of life in diabetes: The associations of complications with EQ-5D scores

Abstract: The aim of this study was to describe how diabetes complications influence the health-related quality of life of individuals with diabetes using the individual EQ-5D dimensions and the EQ-5D index. We mailed a questionnaire to 1,000 individuals with diabetes type 1 and 2 in Norway. The questionnaire had questions about socio-demographic characteristics, use of health care, diabetes complications and finally the EQ-5D descriptive system. Logistic regressions were used to explore determinants of responses in the EQ-5D dimensions, and robust linear regression was used to explore determinants of the EQ-5D index. In multivariate analyses the strongest determinants of reduced MOBILITY were neuropathy and ischemic heart disease. In the ANXIETY/DEPRESSION dimension of the EQ-5D, "fear of hypoglycaemia" was a strong determinant. For those without complications, the EQ-5D index was 0.90 (type 1 diabetes) and 0.85 (type 2 diabetes). For those with complications, the EQ-5D index was 0.68 (type 1 diabetes) and 0.73 (type 2 diabetes). In the linear regression the factors with the greatest negative impact on the EQ-5D index were ischemic heart disease (type 1 diabetes), stroke (both diabetes types), neuropathy (both diabetes types), and fear of hypoglycaemia (type 2 diabetes). The EQ-5D dimensions and the EQ-5D seem capable of capturing the consequences of diabetes-related complications, and such complications may have substantial impact on several dimensions of health-related quality of life (HRQoL). The strongest determinants of reduced HRQoL in people with diabetes were ischemic heart disease, stroke and neuropathy.

Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study.

Abstract: Background Although animal studies have indicated that general anesthetics may result in widespread apoptotic neurodegeneration and neurocognitive impairment in the developing brain, results from human studies are scarce. We investigated the association between exposure to surgery and anesthesia for inguinal hernia repair in infancy and subsequent academic performance. Methods Using Danish birth cohorts from 1986-1990, we compared the academic performance of all children who had undergone inguinal hernia repair in infancy to a randomly selected, age-matched 5% population sample. Primary analysis compared average test scores at ninth grade adjusting for sex, birth weight, and paternal and maternal age and education. Secondary analysis compared the proportions of children not attaining test scores between the two groups. Results From 1986-1990 in Denmark, 2,689 children underwent inguinal hernia repair in infancy. A randomly selected, age-matched 5% population sample consists of 14,575 individuals. Although the exposure group performed worse than the control group (average score 0.26 lower; 95% CI, 0.21-0.31), after adjusting for known confounders, no statistically significant difference (-0.04; 95% CI, -0.09 to 0.01) between the exposure and control groups could be demonstrated. However, the odds ratio for test score nonattainment associated with inguinal hernia repair was 1.18 (95% CI, 1.04-1.35). Excluding from analyses children with other congenital malformations, the difference in mean test scores remained nearly unchanged (0.05; 95% CI, 0.00-0.11). In addition, the increased proportion of test score nonattainment within the exposure group was attenuated (odds ratio = 1.13; 95% CI, 0.98-1.31). Conclusion In the ethnically and socioeconomically homogeneous Danish population, we found no evidence that a single, relatively brief anesthetic exposure in connection with hernia repair in infancy reduced academic performance at age 15 or 16 yr after adjusting for known confounding factors. However, the higher test score nonattainment rate among the hernia group could suggest that a subgroup of these children are developmentally disadvantaged compared with the background population.