Opin vísindi
Opin vísindi er varðveislusafn vísindaefnis og doktorsritgerða í opnum aðgangi á vegum íslenskra háskóla og Landsbókasafns Íslands - Háskólabókasafns.
Opinn aðgangur að rannsóknaniðurstöðum er í samræmi við 10. gr. laga nr. 3/2003 um opinberan stuðning við vísindarannsóknir sem og kröfur innlendra og erlendra rannsóknasjóða. Markmiðið með opnum aðgangi er að niðurstöður rannsókna séu aðgengilegar sem flestum óhindrað og án endurgjalds á rafrænu formi. Vistun í varðveislusafninu er varanleg og ætlað að tryggja aðgang að vísindaefni íslenskra háskóla í opnum aðgangi um ókomna tíð. Varðveislusafnið Opin vísindi er tengt við rannsóknagáttina IRIS og rannsóknaniðurstöður í opnum aðgangi sem eru skráðar í IRIS eru um leið vistaðar og gerðar aðgengilegar til framtíðar í varðveislusafninu. Með því að safna þessu efni saman í eitt safn verður aðgangur að því einfaldur og þægilegur fyrir alla sem vilja kynna sér það og geta þannig notið þess öfluga vísindastarfs sem fram fer í háskólum landsins.
Varðveislusafnið er OpenAIRE / OpenAIREplus samhæft og samrýmist kröfum sem gerðar eru um birtingu rannsóknaniðurstaðna úr verkefnum sem styrkt eru úr evrópsku rannsóknaáætlununum FP7 og H2020.
Varðveislusafnið notar opna hugbúnaðinn DSpace.
Opinn aðgangur að rannsóknaniðurstöðum er í samræmi við 10. gr. laga nr. 3/2003 um opinberan stuðning við vísindarannsóknir sem og kröfur innlendra og erlendra rannsóknasjóða. Markmiðið með opnum aðgangi er að niðurstöður rannsókna séu aðgengilegar sem flestum óhindrað og án endurgjalds á rafrænu formi. Vistun í varðveislusafninu er varanleg og ætlað að tryggja aðgang að vísindaefni íslenskra háskóla í opnum aðgangi um ókomna tíð. Varðveislusafnið Opin vísindi er tengt við rannsóknagáttina IRIS og rannsóknaniðurstöður í opnum aðgangi sem eru skráðar í IRIS eru um leið vistaðar og gerðar aðgengilegar til framtíðar í varðveislusafninu. Með því að safna þessu efni saman í eitt safn verður aðgangur að því einfaldur og þægilegur fyrir alla sem vilja kynna sér það og geta þannig notið þess öfluga vísindastarfs sem fram fer í háskólum landsins.
Varðveislusafnið er OpenAIRE / OpenAIREplus samhæft og samrýmist kröfum sem gerðar eru um birtingu rannsóknaniðurstaðna úr verkefnum sem styrkt eru úr evrópsku rannsóknaáætlununum FP7 og H2020.
Varðveislusafnið notar opna hugbúnaðinn DSpace.
Flokkar í Opnum vísindum
Veldu flokk til að skoða.
- University of Iceland
- University of Akureyri
- Bifröst University
- Hólar University College
- Reykjavík University
- IRIS
- Agricultural University of Iceland
- National and University Library of Iceland
- Iceland University of the Arts
Nýlega bætt við
Changes in antibiotic prescribing following COVID-19 restrictions : Lessons for post-pandemic antibiotic stewardship
(2021-08-17) Gillies, Malcolm B.; Burgner, David P.; Ivancic, Lorraine; Nassar, Natasha; Miller, Jessica E.; Sullivan, Sheena G.; Todd, Isobel T.M.; Pearson, Sallie Anne; Schaffer, Andrea L.; Zoéga, Helga; Faculty of Medicine
Aims: Public health responses to reduce SARS-CoV-2 transmission have profoundly affected the epidemiology and management of other infections. We examined the impact of COVID-19 restrictions on antibiotic dispensing in Australia. Methods: We used national claims data to investigate antibiotic dispensing trends from November 2015 to October 2020 and whether changes reflected reductions in primary care consultations. We used interrupted time series analysis to quantify changes in monthly antibiotic dispensing and face-to-face and telehealth GP consultations and examined changes by recipient age, pharmacy State and prescriber specialty. Results: Over the study period, an estimated 19 921 370 people had 125 495 137 antibiotic dispensings, 71% prescribed by GPs. Following COVID-19 restrictions, we observed a sustained 36% (95% CI: 33–40%) reduction in antibiotic dispensings from April 2020. Antibiotics recommended for managing respiratory tract infections showed large reductions (range 51–69%), whereas those recommended for non-respiratory infections were unchanged. Dispensings prescribed by GPs decreased from 63.5 per 1000 population for April–October 2019 to 37.0 per 1000 for April–October 2020. Total GP consultation rates remained stable, but from April 2020, 31% of consultations were telehealth. Conclusion: In a setting with a low COVID-19 incidence, restrictions were associated with a substantial reduction in community dispensings of antibiotics primarily used to treat respiratory infections, coincident with reported reductions in respiratory viral infections. Our findings are informative for post-pandemic antimicrobial stewardship and highlight the potential to reduce inappropriate prescribing by GPs and specialists for respiratory viral infections.
Haploinsufficiency of KMT2D is sufficient to cause Kabuki syndrome and is compatible with life
(2020-02-01) Luperchio, Teresa Romeo; Applegate, Carolyn D.; Bodamer, Olaf; Björnsson, Hans Tómas; Faculty of Medicine
Promoter CpG Density Predicts Downstream Gene Loss-of-Function Intolerance
(2020-09-03) Boukas, Leandros; Björnsson, Hans Tómas; Hansen, Kasper D.; Faculty of Medicine
The aggregation and joint analysis of large numbers of exome sequences has recently made it possible to derive estimates of intolerance to loss-of-function (LoF) variation for human genes. Here, we demonstrate strong and widespread coupling between genic LoF intolerance and promoter CpG density across the human genome. Genes downstream of the most CpG-rich promoters (top 10% CpG density) have a 67.2% probability of being highly LoF intolerant, using the LOEUF metric from gnomAD. This is in contrast to 7.4% of genes downstream of the most CpG-poor (bottom 10% CpG density) promoters. Combining promoter CpG density with exonic and promoter conservation explains 33.4% of the variation in LOEUF, and the contribution of CpG density exceeds the individual contributions of exonic and promoter conservation. We leverage this to train a simple and easily interpretable predictive model that outperforms other existing predictors and allows us to classify 1,760 genes—which are currently unascertained in gnomAD—as highly LoF intolerant or not. These predictions have the potential to aid in the interpretation of novel variants in the clinical setting. Moreover, our results reveal that high CpG density is not merely a generic feature of human promoters but is preferentially encountered at the promoters of the most selectively constrained genes, calling into question the prevailing view that CpG islands are not subject to selection.
Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome
(2021-03-12) Zhang, Li; Pilarowski, Genay; Pich, Emilio Merlo; Nakatani, Atsushi; Dunlop, John; Baba, Rina; Matsuda, Satoru; Daini, Masaki; Hattori, Yasushi; Matsumoto, Shigemitsu; Ito, Mitsuhiro; Kimura, Haruhide; Björnsson, Hans Tómas; Faculty of Medicine
Kabuki syndrome (KS) is a rare cause of intellectual disability primarily caused by loss-of-function mutations in lysine-specific methyltransferase 2D ( KMT2D), which normally adds methyl marks to lysine 4 on histone 3. Previous studies have shown that a mouse model of KS ( Kmt2d +/βGeo ) demonstrates disruption of adult neurogenesis and hippocampal memory. Proof-of-principle studies have shown postnatal rescue of neurological dysfunction following treatments that promote chromatin opening; however, these strategies are non-specific and do not directly address the primary defect of histone methylation. Since lysine-specific demethylase 1A (LSD1/KDM1A) normally removes the H3K4 methyl marks added by KMT2D, we hypothesized that inhibition of KDM1A demethylase activity may ameliorate molecular and phenotypic defects stemming from KMT2D loss. To test this hypothesis, we evaluated a recently developed KDM1A inhibitor (TAK-418) in Kmt2d +/βGeo mice. We found that orally administered TAK-418 increases the numbers of newly born doublecortin (DCX) + cells and processes in the hippocampus in a dose-dependent manner. We also observed TAK-418-dependent rescue of histone modification defects in hippocampus both by western blot and chromatin immunoprecipitation sequencing (ChIP-seq). Treatment rescues gene expression abnormalities including those of immediate early genes such as FBJ osteosarcoma oncogene ( Fos) and FBJ osteosarcoma oncogene homolog B ( Fosb). After 2 weeks of TAK-418, Kmt2d +/βGeo mice demonstrated normalization of hippocampal memory defects. In summary, our data suggest that KDM1A inhibition is a plausible treatment strategy for KS and support the hypothesis that the epigenetic dysregulation secondary to KMT2D dysfunction plays a major role in the postnatal neurological disease phenotype in KS.
Clinical delineation, sex differences, and genotype–phenotype correlation in pathogenic KDM6A variants causing X-linked Kabuki syndrome type 2
(2021-07) Faundes, Víctor; Goh, Stephanie; Akilapa, Rhoda; Bezuidenhout, Heidre; Björnsson, Hans Tómas; Bradley, Lisa; Brady, Angela F.; Brischoux-Boucher, Elise; Brunner, Han; Bulk, Saskia; Canham, Natalie; Cody, Declan; Dentici, Maria Lisa; Digilio, Maria Cristina; Elmslie, Frances; Fry, Andrew E.; Gill, Harinder; Hurst, Jane; Johnson, Diana; Julia, Sophie; Lachlan, Katherine; Lebel, Robert Roger; Byler, Melissa; Gershon, Eric; Lemire, Edmond; Gnazzo, Maria; Lepri, Francesca Romana; Marchese, Antonia; McEntagart, Meriel; McGaughran, Julie; Mizuno, Seiji; Okamoto, Nobuhiko; Rieubland, Claudine; Rodgers, Jonathan; Sasaki, Erina; Scalais, Emmanuel; Scurr, Ingrid; Suri, Mohnish; van der Burgt, Ineke; Matsumoto, Naomichi; Miyake, Noriko; Benoit, Valérie; Lederer, Damien; Banka, Siddharth; Faculty of Medicine
Purpose: The variant spectrum and the phenotype of X-linked Kabuki syndrome type 2 (KS2) are poorly understood. Methods: Genetic and clinical details of new and published individuals with pathogenic KDM6A variants were compiled and analyzed. Results: Sixty-one distinct pathogenic KDM6A variants (50 truncating, 11 missense) from 80 patients (34 males, 46 females) were identified. Missense variants clustered in the TRP 2, 3, 7 and Jmj-C domains. Truncating variants were significantly more likely to be de novo. Thirteen individuals had maternally inherited variants and one had a paternally inherited variant. Neonatal feeding difficulties, hypoglycemia, postnatal growth retardation, poor weight gain, motor delay, intellectual disability (ID), microcephaly, congenital heart anomalies, palate defects, renal malformations, strabismus, hearing loss, recurrent infections, hyperinsulinism, seizures, joint hypermobility, and gastroesophageal reflux were frequent clinical findings. Facial features of over a third of patients were not typical for KS. Males were significantly more likely to be born prematurely, have shorter stature, and severe developmental delay/ID. Conclusion: We expand the KDM6A variant spectrum and delineate the KS2 phenotype. We demonstrate that the variability of the KS2 phenotypic depends on sex and the variant type. We also highlight the overlaps and differences between the phenotypes of KS2 and KS1.