LifeGene : a large prospective population-based study of global relevance

Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enroll 500,000 Swedes and follow them longitudinally for at least 20 years.Stockholm County CouncilVetenskapsrådetKarolinska InstitutetTorsten and Ragnar Söderbergs FoundationAFA FörsäkringarManuscrip

”Där är jag faktiskt inte riktigt nöjd med min insats” – en studie om hur lärare hanterar elevers läs- och skrivsvårigheter,

Abstrakt Linda Karlsson & Markus Palmgren: ”Där är jag faktiskt inte riktigt nöjd med min insats” – en studie om hur lärare hanterar elevers läs- och skrivsvårigheter, examensarbete 10 poäng, Göteborgs Universitet, 2006 Nyckelord: Läs- och skrivsvårigheter, läs- och skrivinlärning, avkodningsinriktad utgångspunkt, helordsinriktad utgångspunkt, dyslexi Syftet med denna studie är att undersöka hur tre skolor i en mindre kommun i Sverige har valt att hantera läs- och skrivsvårigheter hos elever i de yngre åldrarna. Hur agerar lärarna för att underlätta för elever med läs- och skrivsvårigheter; ändrar de sin undervisningsmetod? Undersökningen är baserad på litteraturstudier samt kvalitativa intervjuer med sex lärare. Resultaten visar att lärarna inte ändrar sitt arbetssätt för att underlätta för de elever som har svårigheter att bemästra skriftspråket. Lärarna väljer istället att ge de elever som får problem med att läsa och skriva antingen kompensatorisk hjälp utanför klassrummet, med hjälp av en specialpedagog/speciallärare, eller enklare uppgifter, och då inom ramen för sin ordinarie undervisningsmetod

The ACA4 Gene of Arabidopsis Encodes a Vacuolar Membrane Calcium Pump That Improves Salt Tolerance in Yeast

Several lines of evidence suggest that regulation of intracellular Ca(2+) levels is crucial for adaptation of plants to environmental stress. We have cloned and characterized Arabidopsis auto-inhibited Ca(2+)-ATPase, isoform 4 (ACA4), a calmodulin-regulated Ca(2+)-ATPase. Confocal laser scanning data of a green fluorescent protein-tagged version of ACA4 as well as western-blot analysis of microsomal fractions obtained from two-phase partitioning and Suc density gradient centrifugation suggest that ACA4 is localized to small vacuoles. The N terminus of ACA4 contains an auto-inhibitory domain with a binding site for calmodulin as demonstrated through calmodulin-binding studies and complementation experiments using the calcium transport yeast mutant K616. ACA4 and PMC1, the yeast vacuolar Ca(2+)-ATPase, conferred protection against osmotic stress such as high NaCl, KCl, and mannitol when expressed in the K616 strain. An N-terminally modified form of ACA4 specifically conferred increased NaCl tolerance, whereas full-length ATPase had less effect

Structure and mechanism of ATP-dependent phospholipid transporters

Background: ATP-binding cassette (ABC) transporters and P4-ATPases are two large and seemingly unrelated families of primary active pumps involved in moving phospholipids from one leaflet of a biological membrane to the other.Scope of review: This review aims to identify common mechanistic features in the way phospholipid flipping is carried out by two evolutionarily unrelated families of transporters.Major conclusions: Both protein families hydrolyze ATP, although they employ different mechanisms to use it, and have a comparable size with twelve transmembrane segments in the functional unit. Further, despite differences in overall architecture, both appear to operate by an alternating access mechanism and during transport they might allow access of phospholipids to the internal part of the transmembrane domain. The latter feature is obvious for ABC transporters, but phospholipids and other hydrophobic molecules have also been found embedded in P-type ATPase crystal structures. Taken together, in two diverse groups of pumps, nature appears to have evolved quite similar ways of flipping phospholipids.General significance: Our understanding of the structural basis for phospholipid flipping is still limited but it seems plausible that a general mechanism for phospholipid flipping exists in nature. This article is part of a Special Issue entitled Structural biochemistry and biophysics of membrane proteins

Yeast Aquaglyceroporins Use the Transmembrane Core to Restrict Glycerol Transport

Aquaglyceroporins are transmembrane proteins belonging to the family of aquaporins, which facilitate the passage of specific uncharged solutes across membranes of cells. The yeast aquaglyceroporin Fps1 is important for osmoadaptation by regulating intracellular glycerol levels during changes in external osmolarity. Upon high osmolarity conditions, yeast accumulates glycerol by increased production of the osmolyte and by restricting glycerol efflux through Fps1. The extended cytosolic termini of Fps1 contain short domains that are important for regulating glycerol flux through the channel. Here we show that the transmembrane core of the protein plays an equally important role. The evidence is based on results from an intragenic suppressor mutation screen and domain swapping between the regulated variant of Fps1 from Saccharomyces cerevisiae and the hyperactive Fps1 ortholog from Ashbya gossypii. This suggests a novel mechanism for regulation of glycerol flux in yeast, where the termini alone are not sufficient to restrict Fps1 transport. We propose that glycerol flux through the channel is regulated by interplay between the transmembrane helices and the termini. This mechanism enables yeast cells to fine-tune intracellular glycerol levels at a wide range of extracellular osmolarities