16 research outputs found
Genome-wide association and functional follow-up reveals new loci for kidney function
Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (PÂ <Â 5Â ĂÂ 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Hur agerar vi nÀr vi ser? : En studie om sjuksköterskors anmÀlningsbenÀgenhet gÀllande barn som far eller riskerar att fara illa
Syfte. Syftet med studien var att kartlÀgga sjuksköterskors anmÀlningsbenÀgenhet angÄende barn som far illa samt jÀmföra anmÀlningsbenÀgenhet avseende arbetsplats, erfarenhet och Älder inom primÀrvÄrden. Bakgrund. Trots rÄdande anmÀlningsplikt gÀllande barn som far eller riskerar att fara illa anmÀls endast en brÄkdel av de fall dÀr misstanke finns. Riktlinjer för tillvÀgagÄngssÀtt saknas ofta och sjuksköterskor utrycker bristande stöd frÄn arbetsgivare och kollegor vid en orosanmÀlan. OsÀkerhet och en vilja att bibehÄlla goda relationer med förÀldrarna leder till minskad benÀgenhet att anmÀla. Design. TvÀrsnittsstudie med enkÀter. Metod. 39 sjuksköterskor, barnsjuksköterskor och distriktssköterskor inom primÀrvÄrden i VÀsterbotten, Sverige besvarade enkÀten. Bakgrundsvariabler och skattning av intervention efter lÀst fallbeskrivning anvÀndes i studien och analyserades med frekvenser, genomsnittsmÄtt, spridningsmÄtt. GruppjÀmförelser utfördes med hjÀlp av Mann-Whitney U-test. Resultat. Sjuksköterskor med lÄng erfarenhet har högre grad av anmÀlningsbenÀgenhet jÀmfört med sjuksköterskor med kort erfarenhet. De avvaktade i lÀgre grad samt tillfrÄgade verksamhetschefen i lÀgre grad jÀmfört med sjuksköterskor med kort erfarenhet. Resultatet visar Àven att yngre sjuksköterskor i högre grad avvaktar och ser hur det utvecklas jÀmfört med Àldre sjuksköterskor. Konklusion. Skillnader i hanteringssÀtt av orosanmÀlan hos sjuksköterskor visar att vem barnet möter har betydelse. Sammantaget ser resultatet av studien ut att peka mot att lÄng erfarenhet och hög Älder Àr betydelsefulla variabler nÀr sjuksköterskor handhar ett Àrende som berör barn som far illa.
Substrate specificities of mouse heparan sulphate glucosaminyl 6-O-sulphotransferases.
Glycosaminoglycan heparan sulphate interacts with a variety of proteins, such as growth factors, cytokines, enzymes and inhibitors and, thus, influences cellular functions, including adhesion, motility, differentiation and morphogenesis. The interactions generally involve saccharide domains in heparan sulphate chains, with precisely located O-sulphate groups. The 6-O-sulphate groups on glucosamine units, supposed to be involved in various interactions of functional importance, occur in different structural contexts. Three isoforms of the glucosaminyl 6-O-sulphotransferase (6-OST) have been cloned and characterized [H. Habuchi, M. Tanaka, O. Habuchi, K. Yoshida, H. Suzuki, K. Ban and K. Kimata (2000) J. Biol. Chem. 275, 2859-2868]. We have studied the substrate specificities of the recombinant enzymes using various O-desulphated poly- and oligo-saccharides as substrates, and using adenosine 3'-phosphate 5'-phospho[(35)S]sulphate as sulphate donor. All three enzymes catalyse 6-O-sulphation of both -GlcA-GlcNS- and -IdoA-GlcNS- (where GlcA represents D-glucuronic acid, NS the N-sulphate group and IdoA the L-iduronic acid) sequences, with preference for IdoA-containing targets, with or without 2-O-sulphate substituents. 6-OST1 showed relatively higher activity towards target sequences lacking 2-O-sulphate, e.g. the -GlcA-GlcNS- disaccharide unit. Sulphation of such non-O-sulphated acceptor sequences was generally favoured at low acceptor polysaccharide concentrations. Experiments using partially O-desulphated antithrombin-binding oligosaccharide as the acceptor revealed 6-O-sulphation of N-acetylated as well as 3-O-sulphated glucosamine residues with each of the three 6-OSTs. We conclude that the three 6-OSTs have qualitatively similar substrate specificities, with minor differences in target preference
The Impact of Estradiol on Bone Mineral Density is modulated by The Specific Estrogen Receptor-{alpha} Cofactor RIZ1 Insertion/Deletion Polymorphism.
Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment
Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells
FramtidsfrÄgor Restaureringskonst 2016-2017 Kungl Konsthögskolan
Restaureringskonst vid Kungl Konsthögskolan i Stockholm har lÀsÄret 2016-2017 haft temat FramtidsfrÄgor. Utöver professionskunskap och teori har fronten och framtidsfrÄgor inom Àmnet studerats. Publikationen visar en del av Ärets arbete i form av artiklar. Praktisk trÀning i dokumentation och vÀrdering avspeglas liksom gemensamma studieresor, förelÀsningar och milstolpar inom restaurering. FramtidsfrÄgor har inga enkla svar med för att kunskapsuppbyggnaden ska ligga i fronten Àr Restaureringskonst en aktiv deltagare i diskussionen