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 (P < 5 × 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 när vi ser? : En studie om sjuksköterskors anmälningsbenägenhet gällande barn som far eller riskerar att fara illa

Syfte. Syftet med studien var att kartlägga sjuksköterskors anmälningsbenägenhet angående barn som far illa samt jämföra anmälningsbenägenhet avseende arbetsplats, erfarenhet och ålder inom primärvården. Bakgrund. Trots rådande anmälningsplikt gällande barn som far eller riskerar att fara illa anmäls endast en bråkdel av de fall där misstanke finns. Riktlinjer för tillvägagångssätt saknas ofta och sjuksköterskor utrycker bristande stöd från arbetsgivare och kollegor vid en orosanmälan. Osäkerhet och en vilja att bibehålla goda relationer med föräldrarna leder till minskad benägenhet att anmäla. Design. Tvärsnittsstudie med enkäter. Metod. 39 sjuksköterskor, barnsjuksköterskor och distriktssköterskor inom primärvården i Västerbotten, Sverige besvarade enkäten. Bakgrundsvariabler och skattning av intervention efter läst fallbeskrivning användes i studien och analyserades med frekvenser, genomsnittsmått, spridningsmått. Gruppjämförelser utfördes med hjälp av Mann-Whitney U-test. Resultat. Sjuksköterskor med lång erfarenhet har högre grad av anmälningsbenägenhet jämfört med sjuksköterskor med kort erfarenhet. De avvaktade i lägre grad samt tillfrågade verksamhetschefen i lägre grad jämfört med sjuksköterskor med kort erfarenhet. Resultatet visar även att yngre sjuksköterskor i högre grad avvaktar och ser hur det utvecklas jämfört med äldre sjuksköterskor. Konklusion. Skillnader i hanteringssätt av orosanmälan hos sjuksköterskor visar att vem barnet möter har betydelse. Sammantaget ser resultatet av studien ut att peka mot att lång erfarenhet och hög ålder är betydelsefulla variabler när sjuksköterskor handhar ett ärende 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

Framtidsfrågor Restaureringskonst 2016-2017 Kungl Konsthögskolan

Restaureringskonst vid Kungl Konsthögskolan i Stockholm har läsåret 2016-2017 haft temat Framtidsfrågor. Utöver professionskunskap och teori har fronten och framtidsfrågor inom ämnet studerats. Publikationen visar en del av årets arbete i form av artiklar. Praktisk träning i dokumentation och värdering avspeglas liksom gemensamma studieresor, föreläsningar och milstolpar inom restaurering. Framtidsfrågor har inga enkla svar med för att kunskapsuppbyggnaden ska ligga i fronten är Restaureringskonst en aktiv deltagare i diskussionen