Uppsala University

About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Gene. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.

A temperature predictor for parallel tempering simulations

Abstract: An algorithm is proposed that generates a set of temperatures for use in parallel tempering simulations (also known as temperature-replica exchange molecular dynamics simulations) of proteins to obtain a desired exchange probability Pdes. The input consists of the number of protein atoms and water molecules in the system, information about the use of constraints and virtual sites and the lower temperature limits. The temperatures generated yield probabilities which are very close to Pdes (correlation 97%), independent of force field and over a wide temperature range. To facilitate its use, the algorithm has been implemented as a web server at http://folding.bmc.uu.se/remd.

Antisense RNA Control in Bacteria, Phages, and Plasmids

Abstract: Antisense RNA control is now recognized as an efficient and specific means of regulating gene expression at the posttranscriptional level. Almost all naturally occurring cases have been found in prokaryotes, often in their accessory genetic elements. Several antisense RNA systems are now well-understood, and these display a spectrum of mechanisms of action, binding pathways, and kinetics. This review summarizes antisense RNA control in prokaryotes, emphasizing the biology of the systems involved.

Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers.

Abstract: This investigation describes the expression and interindividual variability in transcript levels of multiple drug efflux systems in the human jejunum and compares the expression profiles in these cells with that of the commonly used Caco-2 cell drug absorption model. Transcript levels of ten-drug efflux proteins of the ATP-binding cassette (ABC) transporter family [MDR1, MDR3, ABCB5, MRP1-6, and breast cancer resistance protein (BCRP)], lung resistance-related protein (LRP), and CYP3A4 were determined using quantitative polymerase chain reaction in jejunal biopsies from 13 healthy human subjects and in Caco-2 cells. All genes except ABCB5 were expressed, and transcript levels varied between individuals only by a factor of 2 to 3. Surprisingly, BCRP and MRP2 transcripts were more abundant in jejunum than MDR1 transcripts. Jejunal transcript levels of the different ABC transporters spanned a range of three log units with the rank order: BCRP approximately MRP2 > MDR1 approximately MRP3 approximately MRP6 approximately MRP5 approximately MRP1 > MRP4 > MDR3. Furthermore, transcript levels of 9 of 10 ABC transporters correlated well between jejunum and Caco-2 cells (r2 = 0.90). However, BCRP exhibited a 100-fold lower transcript level in Caco-2 cells compared with jejunum. Thus, the expression of a number of efflux protein transcripts in jejunum are equal to, or even higher than, that of MDR1, suggesting that the roles of these proteins (in particular BCRP and MRP2) in intestinal drug efflux have been underestimated. Also, we tentatively conclude that the Caco-2 cell line is a useful model of jejunal drug efflux, if the low expression of BCRP is taken into account.

Binding of Drugs to Human Serum Albumin:: XI. The Specificity of Three Binding Sites as Studied with Albumin Immobilized in Microparticles

Abstract: Human serum albumin can be immobilized in spherical, macroporous microparticles of polyacrylamide of about 1 µm in diameter with retention of its native properties. It has been shown that diazepam, digitoxin and warfarin independently bind to albumin and can conveniently be used as markers of three separate, discrete binding sites on albumin. A simple technique has been devised by which the capacity of about 140 drugs and other compounds to affect the binding of the radioactively labeled markers has been studied. Some drugs, e.g. antirheumatic drugs of the isopropionic acid-type, some antidiabetic agents, penicillin derivatives, benzodiazepines, tryptophan, dansylsarcosine, and suiphobromophthalein efficiently displace diazepam. Other drugs, e.g., some diuretics, sulpha drugs, phenytoin, salicylic acid and butazone derivatives, azapropazoe, bilirubin, and dansylamide displace warfarin. Displacement of digitoxin is less common. In some cases the binding of the markers is improved, e.g., tamoxifen increases the binding of warfarin. Both competitive and allosteric mechanisms are responsible for the changed binding of the markers. Some results suggest the presence of more than the three binding sites for drugs on the albumin surface studied with diazepam, digitoxin and warfarin.

Neurodevelopmental Outcome in Extremely Preterm Infants at 2.5 Years After Active Perinatal Care in Sweden

Abstract: Importance Active perinatal care increases survival of extremely preterm infants; however, improved survival might be associated with increased disability among survivors Objective To determine neurodevelopmental outcome in extremely preterm children at 25 years (corrected age) Design, Setting, and Participants Population-based prospective cohort of consecutive extremely preterm infants born before 27 weeks of gestation in Sweden between 2004 and 2007 Of 707 live-born infants, 491 (69%) survived to 25 years Survivors were assessed and compared with singleton control infants who were born at term and matched by sex, ethnicity, and municipality Assessments ended in February 2010 and comparison estimates were adjusted for demographic differences Main Outcomes and Measures Cognitive, language, and motor development was assessed with Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), which are standardized to mean (SD) scores of 100 (15) Clinical examination and parental questionnaires were used for diagnosis of cerebral palsy and visual and hearing impairments Assessments were made by week of gestational age Results At a median age of 305 months (corrected), 456 of 491 (94%) extremely preterm children were evaluated (41 by chart review only) For controls, 701 had information on health status and 366 had Bayley-III assessments Mean (SD) composite Bayley-III scores (cognition, 94 [123]; language, 98 [165]; motor, 94 [159]) were lower than the corresponding mean scores for controls (cognition, 104 [106]; P < 001; adjusted difference in mean scores, 92 [99% CI, 69-115]; language, 109 [123]; P < 001; adjusted difference in mean scores, 93 [99% Cl, 64-123]; and motor, 107 [137]; P < 001; adjusted difference in mean scores, 126 [99% Cl, 95-156]) Cognitive disability was moderate in 5% of the extremely preterm group vs 03% in controls (P < 001) and it was severe in 63% of the extremely preterm group vs 03% in controls (P < 001) Language disability was moderate in 94% of the extremely preterm group vs 25% in controls (P < 001) and severe in 66% of the extremely preterm group vs 0% in controls (P < 001) Other comparisons between the extremely preterm group vs controls were for cerebral palsy (70% vs 01%; P < 001), for blindness (09% vs 0%; P = 02), and for hearing impairment (moderate and severe, 09% vs 0%; P = 02, respectively) Overall, 42% (99% CI, 36%-48%) of extremely preterm children had no disability, 31% (99% CI, 25%-36%) had mild disability, 16% (99% CI, 12%-21%) had moderate disability, and 11% (99% CI, 72%-15%) had severe disability Moderate or severe overall disability decreased with gestational age at birth (22 weeks, 60%; 23 weeks, 51%; 24 weeks, 34%; 25 weeks, 27%; and 26 weeks, 17%; P for trend < 001) Conclusions and Relevance Of children born extremely preterm and receiving active perinatal care, 73% had mild or no disability and neurodevelopmental outcome improved with each week of gestational age These results are relevant for clinicians counseling families facing extremely preterm birth JAMA 2013;309(17):1810-1820