| 1. |
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| 2. |
- Justice, A. E., et al.
(författare)
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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| 3. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 4. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 5. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 6. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 7. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
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Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
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Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
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| 8. |
- Coviello, Andrea D, et al.
(författare)
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A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
- 2012
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p=1.8×10(-106)), PRMT6 (rs17496332, 1p13.3, p=1.4×10(-11)), GCKR (rs780093, 2p23.3, p=2.2×10(-16)), ZBTB10 (rs440837, 8q21.13, p=3.4×10(-09)), JMJD1C (rs7910927, 10q21.3, p=6.1×10(-35)), SLCO1B1 (rs4149056, 12p12.1, p=1.9×10(-08)), NR2F2 (rs8023580, 15q26.2, p=8.3×10(-12)), ZNF652 (rs2411984, 17q21.32, p=3.5×10(-14)), TDGF3 (rs1573036, Xq22.3, p=4.1×10(-14)), LHCGR (rs10454142, 2p16.3, p=1.3×10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p=2.7×10(-08)), and UGT2B15 (rs293428, 4q13.2, p=5.5×10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p=2.5×10(-08), women p=0.66, heterogeneity p=0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ∼15.6% and ∼8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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| 9. |
- Ashar, Foram N., et al.
(författare)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 10. |
- Meuller, Bengt, et al.
(författare)
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Review of Spark Discharge Generators for Production of Nanoparticle Aerosols
- 2012
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Ingår i: Aerosol Science and Technology. - : Informa UK Limited. - 1521-7388 .- 0278-6826. ; 46:11, s. 1256-1270
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Forskningsöversikt (refereegranskat)abstract
- In the growing field of nanotechnology there is an increasing need to develop production methods for nanoparticles, especially methods that provide control and reproducibility. The spark discharge generator (SDG) is a versatile device for the production of nanoparticle aerosols. It can produce aerosol nanoparticles in the entire nanometer range (1-100 nm), and beyond. Depending on requirements, and the system used, these nanoparticles can be completely contamination free and composed of one or more materials. This provides a unique opportunity to create new materials on the nanoscale. Already in use in semiconductor, materials, health and environmental research, the SDG shows promise for yet more applications. If needed, particle production by the SDG could be scaled up using parallel generators facilitating continuous high-volume production of aerosol nanoparticles. Still, there is a surprisingly low knowledge of fundamental processes in the SDG. In this article we present a thorough review of the most common and relevant SDGs and the theory of their operation. Some possible improvements are also discussed.
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| 11. |
- Wang, Thomas J, et al.
(författare)
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Common genetic determinants of vitamin D insufficiency: a genome-wide association study.
- 2010
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Ingår i: Lancet. - 1474-547X. ; 376:9736, s. 180-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Vitamin D is crucial for maintenance of musculoskeletal health, and might also have a role in extraskeletal tissues. Determinants of circulating 25-hydroxyvitamin D concentrations include sun exposure and diet, but high heritability suggests that genetic factors could also play a part. We aimed to identify common genetic variants affecting vitamin D concentrations and risk of insufficiency. METHODS: We undertook a genome-wide association study of 25-hydroxyvitamin D concentrations in 33 996 individuals of European descent from 15 cohorts. Five epidemiological cohorts were designated as discovery cohorts (n=16 125), five as in-silico replication cohorts (n=9367), and five as de-novo replication cohorts (n=8504). 25-hydroxyvitamin D concentrations were measured by radioimmunoassay, chemiluminescent assay, ELISA, or mass spectrometry. Vitamin D insufficiency was defined as concentrations lower than 75 nmol/L or 50 nmol/L. We combined results of genome-wide analyses across cohorts using Z-score-weighted meta-analysis. Genotype scores were constructed for confirmed variants. FINDINGS: Variants at three loci reached genome-wide significance in discovery cohorts for association with 25-hydroxyvitamin D concentrations, and were confirmed in replication cohorts: 4p12 (overall p=1.9x10(-109) for rs2282679, in GC); 11q12 (p=2.1x10(-27) for rs12785878, near DHCR7); and 11p15 (p=3.3x10(-20) for rs10741657, near CYP2R1). Variants at an additional locus (20q13, CYP24A1) were genome-wide significant in the pooled sample (p=6.0x10(-10) for rs6013897). Participants with a genotype score (combining the three confirmed variants) in the highest quartile were at increased risk of having 25-hydroxyvitamin D concentrations lower than 75 nmol/L (OR 2.47, 95% CI 2.20-2.78, p=2.3x10(-48)) or lower than 50 nmol/L (1.92, 1.70-2.16, p=1.0x10(-26)) compared with those in the lowest quartile. INTERPRETATION: Variants near genes involved in cholesterol synthesis, hydroxylation, and vitamin D transport affect vitamin D status. Genetic variation at these loci identifies individuals who have substantially raised risk of vitamin D insufficiency. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).
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| 12. |
- Bacou, Marion, et al.
(författare)
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Development of Preclinical Ultrasound Imaging Techniques to Identify and Image Sentinel Lymph Nodes in a Cancerous Animal Model
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Lymph nodes (LNs) are believed to be the first organs targeted by colorectal cancer cells detached from a primary solid tumor because of their role in draining interstitial fluids. Better detection and assessment of these organs have the potential to help clinicians in stratification and designing optimal design of oncological treatments for each patient. Whilst highly valuable for the detection of primary tumors, CT and MRI remain limited for the characterization of LNs. B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) can improve the detection of LNs and could provide critical complementary information to MRI and CT scans; however, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines advise that further evidence is required before US or CEUS can be recommended for clinical use. Moreover, knowledge of the lymphatic system and LNs is relatively limited, especially in preclinical models. In this pilot study, we have created a mouse model of metastatic cancer and utilized 3D high-frequency ultrasound to assess the volume, shape, and absence of hilum, along with CEUS to assess the flow dynamics of tumor-free and tumor-bearing LNs in vivo. The aforementioned parameters were used to create a scoring system to predict the likelihood of a disease-involved LN before establishing post-mortem diagnosis with histopathology. Preliminary results suggest that a sum score of parameters may provide a more accurate diagnosis than the LN size, the single parameter currently used to predict the involvement of an LN in disease.
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| 13. |
- Bollati, Michela, et al.
(författare)
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Structure and functionality in flavivirus NS-proteins : perspectives for drug design
- 2010
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Ingår i: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 87:2, s. 125-148
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Forskningsöversikt (refereegranskat)abstract
- Flaviviridae are small enveloped viruses hosting a positive-sense single-stranded RNA genome. Besides yellow fever virus, a landmark case in the history of virology, members of the Flavivirus genus, such as West Nile virus and dengue virus, are increasingly gaining attention due to their re-emergence and incidence in different areas of the world. Additional environmental and demographic considerations suggest that novel or known flaviviruses will continue to emerge in the future. Nevertheless, up to few years ago flaviviruses were considered low interest candidates for drug design. At the start of the European Union VIZIER Project, in 2004, just two crystal structures of protein domains from the flaviviral replication machinery were known. Such pioneering studies, however, indicated the flaviviral replication complex as a promising target for the development of antiviral compounds. Here we review structural and functional aspects emerging from the characterization of two main components (NS3 and NS5 proteins) of the flavivirus replication complex. Most of the reviewed results were achieved within the European Union VIZIER Project, and cover topics that span from viral genomics to structural biology and inhibition mechanisms. The ultimate aim of the reported approaches is to shed light on the design and development of antiviral drug leads.
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| 14. |
- Dreja, Karl, et al.
(författare)
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Njursjukdomar
- 2016
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 457-482
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Bokkapitel (populärvet., debatt m.m.)
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| 15. |
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| 16. |
- Drevenhorn, Eva, et al.
(författare)
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Risk för ohälsa
- 2016
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Ingår i: Omvårdnad och medicin. - : Studentlitteratur AB. - 9789144076645 ; , s. 73-92
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
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| 17. |
- Fornes, R., et al.
(författare)
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Maternal testosterone and placental function: Effect of electroacupuncture on placental expression of angiogenic markers and fetal growth
- 2016
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 0303-7207 .- 1872-8057. ; 433:C, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Women with polycystic ovary syndrome (PCOS) have elevated circulating androgens during pregnancy and are at an increased risk of adverse pregnancy outcomes. Here we tested the hypotheses that maternal androgen excess decrease placental and fetal growth, and placental expression of markers of steroidogenesis, angiogenesis and sympathetic activity, and that acupuncture with low-frequency electrical stimulation prevents these changes. Pregnant rats were exposed to vehicle or testosterone on gestational day (GD)15-19. Low-frequency electroacupuncture (EA) or handling, as a control for the EA procedure, was given to control or testosterone exposed dams on GD16-20. On GD21, blood pressure was measured and maternal blood, fetuses and placentas collected. Placental steroid receptor expression and proteins involved in angiogenic, neurotrophic and adrenergic signaling were analyzed. EA did not affect any variables in control rats except maternal serum corticosterone, which was reduced. EA in testosterone exposed dams compared with controls increased systolic pressure by 30%, decreased circulating norepinephrine and corticosterone, fetal and placental weight and placental VEGFR1 and proNGF protein expression, and increased the VEGFA/VEGFR1 ratio, mature NGF (mNGF) and the mNGF/proNGF ratio. In conclusion, low-frequency EA in control animals did not have any negative influence on any of the studied variables. In contrast, EA in pregnant dams exposed to testosterone increased blood pressure and impaired placental growth and function, leading to decreased fetal growth. (C) 2016 Published by Elsevier Ireland Ltd.
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| 18. |
- Fornes, R., et al.
(författare)
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The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4-10 weeks, and then mated. On gestational day (GD) 15.5-17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.
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| 19. |
- Gagnemo Persson, Rebecca, et al.
(författare)
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Lungsjukdomar
- 2016. - 1
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Ingår i: Omvårdnad och medicin. - 9789144076645 ; , s. 281-311
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Bokkapitel (populärvet., debatt m.m.)
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| 20. |
- Gagnemo Persson, Rebecca, et al.
(författare)
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Läkemedel
- 2016. - 1
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 125-138
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Bokkapitel (populärvet., debatt m.m.)
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| 21. |
- Jönsson, Ann-Cathrin, et al.
(författare)
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Neurologiska sjukdomar
- 2016. - 1
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 155-190
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Bokkapitel (populärvet., debatt m.m.)
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| 22. |
- Jönsson, Ann-Cathrin, et al.
(författare)
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Stroke
- 2016
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 191-214
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Bokkapitel (populärvet., debatt m.m.)
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| 23. |
- Kanoni, Stavroula, et al.
(författare)
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Analysis with the exome array identifies multiple new independent variants in lipid loci
- 2016
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:18, s. 4094-4106
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Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
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| 24. |
- Klintman, Jenny, et al.
(författare)
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Blodsjukdomar
- 2016. - 1
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Ingår i: Omvårdnad & medicin. - 9789144076645 ; , s. 587-621
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Bokkapitel (populärvet., debatt m.m.)
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| 25. |
- Lin, Yao-Cheng, et al.
(författare)
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Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 115:46, s. E10970-E10978
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Tidskriftsartikel (refereegranskat)abstract
- The Populus genus is one of the major plant model systems, but genomic resources have thus far primarily been available for poplar species, and primarily Populus trichocarpa (Torr. & Gray), which was the first tree with a whole-genome assembly. To further advance evolutionary and functional genomic analyses in Populus, we produced genome assemblies and population genetics resources of two aspen species, Populus tremula L. and Populus tremuloides Michx. The two aspen species have distributions spanning the Northern Hemisphere, where they are keystone species supporting a wide variety of dependent communities and produce a diverse array of secondary metabolites. Our analyses show that the two aspens share a similar genome structure and a highly conserved gene content with P. trichocarpa but display substantially higher levels of heterozygosity. Based on population resequencing data, we observed widespread positive and negative selection acting on both coding and noncoding regions. Furthermore, patterns of genetic diversity and molecular evolution in aspen are influenced by a number of features, such as expression level, coexpression network connectivity, and regulatory variation. To maximize the community utility of these resources, we have integrated all presented data within the PopGenIE web resource (PopGenIE.org).
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| 26. |
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| 27. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Genetic determinants of serum testosterone concentrations in men.
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n=871) and two de novo replication cohorts (n=4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p=1.2×10(-41) and rs6258, p=2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p=5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
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| 28. |
- Andersson, Anna M, et al.
(författare)
-
Electrochemically lithiated graphite characterised by photoelectron spectroscopy
- 2003
-
Ingår i: Journal of Power Sources. - 0378-7753 .- 1873-2755. ; 119-121, s. 522-527
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray photoelectron spectroscopy (XPS) has been used to study the depth profile of the solid–electrolyte interphase (SEI) formed on a graphite powder electrode in a Li-ion battery. The morphology of the SEI-layer, formed in a 1 M LiBF4 EC/DMC 2:1 solution, consists of a 900 Å porous layer of polymers (polyethylene oxide) and a 15–20 Å thin layer of Li2CO3 and LiBF4 reduction–decomposition products. Embedded LiF crystals as large as 0.2 μm were found in the polymer matrix. LiOH and Li2O are not major components on the surface but rather found as a consequence of sputter-related reactions. Monochromatised Al Kα XPS-analysis based on the calibration of Ar+ ion sputtering of model compounds combined with a depth profile analysis based on energy tuning of synchrotron XPS can describe the highly complex composition and morphology of the SEI-layer.
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| 29. |
- Attauabi, Mohamed, et al.
(författare)
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Influence of Genetics, Immunity and the Microbiome on the Prognosis of Inflammatory Bowel Disease (IBD Prognosis Study) : the protocol for a Copenhagen IBD Inception Cohort Study
- 2022
-
Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:6, s. e055779-e055779
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Inflammatory bowel diseases (IBD), encompassing Crohn's disease and ulcerative colitis, are chronic, inflammatory diseases of the gastrointestinal tract. We have initiated a Danish population-based inception cohort study aiming to investigate the underlying mechanisms for the heterogeneous course of IBD, including need for, and response to, treatment.Methods and analysis: IBD Prognosis Study is a prospective, population-based inception cohort study of unselected, newly diagnosed adult, adolescent and paediatric patients with IBD within the uptake area of Hvidovre University Hospital and Herlev University Hospital, Denmark, which covers approximately 1 050 000 inhabitants (~20% of the Danish population). The diagnosis of IBD will be according to the Porto diagnostic criteria in paediatric and adolescent patients or the Copenhagen diagnostic criteria in adult patients. All patients will be followed prospectively with regular clinical examinations including ileocolonoscopies, MRI of the small intestine, validated patient-reported measures and objective examinations with intestinal ultrasound. In addition, intestinal biopsies from ileocolonoscopies, stool, rectal swabs, saliva samples, swabs of the oral cavity and blood samples will be collected systematically for the analysis of biomarkers, microbiome and genetic profiles. Environmental factors and quality of life will be assessed using questionnaires and, when available, automatic registration of purchase data. The occurrence and course of extraintestinal manifestations will be evaluated by rheumatologists, dermatologists and dentists, and assessed by MR cholangiopancreatography, MR of the spine and sacroiliac joints, ultrasonography of peripheral joints and entheses, clinical oral examination, as well as panoramic radiograph of the jaws. Fibroscans and dual-energy X-ray absorptiometry scans will be performed to monitor occurrence and course of chronic liver diseases, osteopenia and osteoporosis.Ethics and dissemination: This study has been approved by Ethics Committee of the Capital Region of Denmark (approval number: H-20065831). Study results will be disseminated through publication in international scientific journals and presentation at (inter)national conferences.
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| 30. |
- Braceras, Inigo, et al.
(författare)
-
On the electro-tribological properties and degradation resistance of silver-aluminum coatings
- 2018
-
Ingår i: Wear. - : ELSEVIER SCIENCE SA. - 0043-1648 .- 1873-2577. ; 414, s. 202-211
-
Tidskriftsartikel (refereegranskat)abstract
- Contact materials in sliding electrical applications must possess low electrical contact resistance, low friction and wear coefficients, and high degradation resistance to the surrounding media. Silver coatings are commonly used in such applications despite their shortcomings. This work has focused on the study of alternative silver-aluminum coatings deposited by PVD. The main findings include the strong dependence of the tribological performance on the concentration of Al and hence the phases present in the coatings. Besides, the wear mechanism was found to be affected by the working media, either on air or insulating oil. Results have shown that for full HCP phase coatings (Ag67Al33), wear rates are lowest, with no adhesive wear and good surface sulphidation resistance, though with some proclivity to oxidation, coupled with a moderate increase in the electrical contact resistance.
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| 31. |
- Davies, Neil, et al.
(författare)
-
The founding charter of the Genomic Observatories Network
- 2014
-
Ingår i: GigaScience. - 2047-217X. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
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| 32. |
- Fadl, Helena, 1965-, et al.
(författare)
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Changing diagnostic criteria for gestational diabetes in Sweden-a stepped wedge national cluster randomised controlled trial-the CDC4G study protocol
- 2019
-
Ingår i: Bmc Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The optimal criteria to diagnose gestational diabetes mellitus (GDM) remain contested. The Swedish National Board of Health introduced the 2013 WHO criteria in 2015 as a recommendation for initiation of treatment for hyperglycaemia during pregnancy. With variation in GDM screening and diagnostic practice across the country, it was agreed that the shift to new guidelines should be in a scientific and structured way. The aim of the Changing Diagnostic Criteria for Gestational Diabetes (CDC4G) in Sweden () is to evaluate the clinical and health economic impacts of changing diagnostic criteria for GDM in Sweden and to create a prospective cohort to compare the many long-term outcomes in mother and baby under the old and new diagnostic approaches. Methods This is a stepped wedge cluster randomised controlled trial, comparing pregnancy outcomes before and after the switch in GDM criteria across 11 centres in a randomised manner. The trial includes all pregnant women screened for GDM across the participating centres during January-December 2018, approximately two thirds of all pregnancies in Sweden in a year. Women with pre-existing diabetes will be excluded. Data will be collected through the national Swedish Pregnancy register and for follow up studies other health registers will be included. Discussion The stepped wedge RCT was chosen to be the best study design for evaluating the shift from old to new diagnostic criteria of GDM in Sweden. The national quality registers provide data on the whole pregnant population and gives a possibility for follow up studies of both mother and child. The health economic analysis from the study will give a solid evidence base for future changes in order to improve immediate pregnancy, as well as long term, outcomes for mother and child.
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| 33. |
- Gennemark, Peter, et al.
(författare)
-
An oral antisense oligonucleotide for PCSK9 inhibition
- 2021
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 13:593
-
Tidskriftsartikel (refereegranskat)abstract
- Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PCSK9 antisense oligonucleotide (ASO) with potential for oral delivery. Past attempts at oral delivery using earlier-generation ASO chemistries and transient permeation enhancers provided encouraging data, suggesting that improving potency of the ASO could make oral delivery a reality. The constrained ethyl chemistry and liver targeting enabled by N-acetylgalactosamine conjugation make this ASO highly potent. A single subcutaneous dose of 90 mg reduced PCSK9 by >90% in humans with elevated LDL cholesterol and a monthly subcutaneous dose of around 25 mg is predicted to reduce PCSK9 by 80% at steady state. To investigate the feasibility of oral administration, the ASO was coformulated in a tablet with sodium caprate as permeation enhancer. Repeated oral daily dosing in dogs resulted in a bioavailability of 7% in the liver (target organ), about fivefold greater than the plasma bioavailability. Target engagement after oral administration was confirmed by intrajejunal administration of a rat-specific surrogate ASO in solution with the enhancer to rats and by plasma PCSK9 and LDL cholesterol lowering in cynomolgus monkey after tablet administration. On the basis of an assumption of 5% liver bioavailability after oral administration in humans, a daily dose of 15 mg is predicted to reduce circulating PCSK9 by 80% at steady state, supporting the development of the compound for oral administration to treat dyslipidemia.
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| 34. |
- Göransson, Katarina, 1974-, et al.
(författare)
-
Triage på akutmottagning
- 2008. - 1
-
Bok (refereegranskat)abstract
- Boken beskriver akutmottagningstriage i detalj; organisationen kring triage och skalor för att gradera patientens medicinska angelägenhetsgrad belyses ur ett internationellt och svenskt perspektiv. Boken tar även upp medicinska aspekter vid akutmottagningstriage; bedömningen av de nyanlända patienterna och hur dessa bör övervakas och utvärderas under vårdtillfället. Organisatoriska aspekter kring akutmottagningstriage som ansvarsfördelning, effekter av triage och utveckling av en triageenhet belyses. Dokumentation kring akutmottagningssjukvård i allmänhet och triage i synnerhet uppmärksammas, liksom omvårdnad vid t.ex. smärta och fallrisk.Boken vänder sig i första hand till sjuksköterskor verksamma på akutmottagningar och inom prehospital verksamhet. Som den första svenska boken i ämnet kan den vara till glädje för övriga yrkesgrupper inom akutsjukvården, för beslutsfattare och för studenter som vill öka sina kunskaper om triage.
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| 35. |
- Hugosson, Håkan Wilhelm, 1972-, et al.
(författare)
-
Theory of phase stabilities and bonding mechanisms in stoichiometric and substoichiometric molybdenum carbide
- 1999
-
Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 86:7, s. 3758-3767
-
Tidskriftsartikel (refereegranskat)abstract
- ABSTRACTFirst principles, total energy methods have been applied to predict the relative stabilities of the four experimentally verified MoC phases: the cubic δ(NaCl) phase and the three hexagonal γ(WC), η and γ′(TiAs) phases. The effect of vacancies on the relative stability of these four phases was investigated using a model structure with ordered vacancies within the carbon sublattice. For stoichiometric MoC, the γ phase was found to be the most stable followed by γ′, δ, and η, but for substoichiometric MoC0.75,MoC0.75, the order of relative stability was changed and the substoichiometric δ phase was found to have the lowest energy followed by γ′ and γ. A study of the electronic structure revealed vacancy induced peaks in the density of state and the electron density attached to these peaks was analyzed and found to emanate from unscreened Mo–Mo bonds through the carbon vacancy site. Finally, the oxygen stabilization of the γ′ MoC phase was studied.
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| 36. |
- Jansson, Agneta K., et al.
(författare)
-
The BH3-only member Noxa may not be involved in the development of unselected colorectal cancer
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Noxa is an BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Further, we searched for mutations in the Noxa gene using single stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumours and decreased in 9% and increased in 16% of the tumours compared to the normal mucosa, but these changes did not have any clinical or pathological significance. We did not find any mutations in the gene. Thus, our observations suggest that the variations in Noxa gene may not be of particular importance in the development of unselected colorectal cancer.
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| 37. |
- Jansson, Anna M
(författare)
-
Inflammatory markers and prognosis in acute coronary syndromes
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Inflammation both accelerates atherosclerosis and contributes to the activation and rupture of the atherosclerotic plaque. Several markers of inflammation, such as CRP, have shown prognostic merit in patients with acute coronary syndromes (ACS). Aims: To investigate the association between circulating levels of some markers with relation to inflammation – osteoprotegerin (OPG), Chemokine (C-X-C motif) ligand 16 (CXCL16) and chromogranin A (CgA) – and prognosis in a population of patients with ACS. Material and methods: Patients aged 18-79 years who were admitted to the coronary care unit at a university hospital with an ACS had blood drawn within 24 hours and after 3 months; echocardiography with determination of the left ventricular ejection fraction (LVEF) was performed within 5 days of admission. Mortality data were obtained from the Swedish National Population Registry and morbidity data from the Swedish Hospital Discharge Registry. The length of follow-up was a median of 81-92 months. Results: Higher OPG levels were associated with an increased likelihood of ST-elevation myocardial infarction (MI), markers of myocardial damage and indices of cardiac dysfunction such as LVEF and B-type natriuretic peptide (BNP). The patients with the higher levels were also more likely to have a history of heart failure (HF) and to be hypotensive on arrival. The circulating OPG levels were predictive of long-term mortality and the incidence of rehospitalization due to HF, a relationship that remained significant after adjustment for clinical risk factors and, in a subgroup where such data were available, after further adjustment for LVEF, CRP, BNP and troponin. The C-statistics of the prognostic information offered by OPG were significantly better than CRP and troponin and similar to BNP and LVEF. For CXCL16, as for OPG, higher levels were associated with higher age and STEMI. CXCL16 predicted long-term mortality, future hospitalizations for HF and new MI, also after adjustment for clinical risk factors. After further adjustments for LVEF, CRP, proBNP and troponin, only the combination of OPG and CXCL16 serum levels predicted cardiovascular (CV) and all-cause mortality, as well as HF rehospitalizations. This was true for both the long term and short term, even after adjustment for the Global Registry of Acute Coronary Events (GRACE) score. Serum levels of OPG and CXCL16 at day 1 and 3 months after ACS were similarly associated with outcome. CgA was also an independent predictor of mortality and HF after adjustments for conventional risk factors, including troponin, and was still significantly associated with mortality after further adjustment for LVEF and proBNP. Conclusions: Even after adjustment for conventional risk markers, serum levels of OPG, CXCL16 and CgA were predictive of long-term mortality and rehospitalizations due to HF in patients with ACS. We also found that a combination of OPG and CXCL16 serum levels was predictive of mortality and HF hospitalizations - and gave more information than each marker alone - in both the long term and the short term, even after adjustment for the GRACE score. Inflammatory markers appear to add prognostic value above and beyond clinical information.
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| 38. |
- Jansson, Anna M, et al.
(författare)
-
Prognostic value of circulating chromogranin A levels in acute coronary syndromes.
- 2009
-
Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 30:1, s. 25-32
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Tidskriftsartikel (refereegranskat)abstract
- To determine whether circulating levels of chromogranin A (CgA) provide prognostic information independently of conventional risk markers in acute coronary syndromes (ACSs).
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| 39. |
- Jansson, Anna M., 1979-
(författare)
-
Structure of Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Has Implications for Coronavirus nsp1 Function and Evolution
- 2013
-
Ingår i: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 87:5, s. 2949-2955
-
Tidskriftsartikel (refereegranskat)abstract
- Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune re- sponse. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome corona- virus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmis- sible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded -barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp113–128. Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.
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| 40. |
- Jansson, Anna M., et al.
(författare)
-
Structure of the methyltransferase domain from the Modoc virus, a flavivirus with no known vector
- 2009
-
Ingår i: Acta Crystallographica Section D. - 0907-4449 .- 1399-0047. ; 65, s. 796-803
-
Tidskriftsartikel (refereegranskat)abstract
- The Modoc virus (MODV) is a flavivirus with no known vector (NKV). Evolutionary studies have shown that the viruses in the MODV group have evolved in association with mammals (bats, rodents) without transmission by an arthropod vector. MODV methyltransferase is the first enzyme from this evolutionary branch to be structurally characterized. The high-resolution structure of the methyltransferase domain of the MODV NS5 protein (MTase(MODV)) was determined. The protein structure was solved in the apo form and in complex with its cofactor S-adenosyl-l-methionine (SAM). Although it belongs to a separate evolutionary branch, MTase(MODV) shares structural characteristics with flaviviral MTases from the other branches. Its capping machinery is a relatively new target in flaviviral drug development and the observed structural conservation between the three flaviviral branches indicates that it may be possible to identify a drug that targets a range of flaviviruses. The structural conservation also supports the choice of MODV as a possible model for flavivirus studies.
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| 41. |
- Jansson, Anna M., 1979-
(författare)
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Targeting Infectious Disease : Structural and functional studies of proteins from two RNA viruses and Mycobacterium tuberculosis
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The recent emergence of a number of new viral diseases as well as the re-emergence of tuberculosis (TB), indicate an urgent need for new drugs against viral and bacterial infections.Coronavirus nsp1 has been shown to induce suppression of host gene expression and interfere with host immune response. However, the mechanism behind this is currently unknown. Here we present the first nsp1 structure from an alphacoronavirus, Transmissible gastroenteritis virus (TGEV) nsp1. Contrary to previous speculation, the TGEV nsp1 structure clearly shows that alpha- and betacoronavirus nsp1s have a common evolutionary origin. However, differences in conservation, shape and surface electrostatics indicate that the mechanism for nsp1-induced suppression of host mRNA translation is likely to be different in the alpha- and betacoronavirus genera.The Modoc virus is a neuroinvasive rodent virus with similar pathology as flavivirus encephalitis in humans. The flaviviral methyltransferase catalyses the two methylations required to complete 5´ mRNA capping, essential for mRNA stability and translation. The structure of the Modoc NS5 methyltransferase domain was determined in complex with its cofactor S-adenosyl-L-methionine. The observed methyltransferase conservation between Modoc and other flaviviral branches, indicates that it may be possible to identify drugs that target a range of flaviviruses and supports the use of Modoc virus as a model for general flaviviral studies.1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is part of the methylerythritol phosphate (MEP) pathway that produces essential precursors for isoprenoid biosynthesis. This pathway is used by a number of pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, but it is not present in humans. Using a structure-based approach, we designed a number of MtDXR inhibitors, including a novel fosmidomycin-analogue that exhibited improved activity against P.falciparum in an in vitro blood cell growth assay. The approach also allowed the first design of an inhibitor that bridge both DXR substrate and co-factor binding sites, providing a stepping-stone for further optimization.
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| 42. |
- Jansson, Anna, 1985, et al.
(författare)
-
Novel Method for Visualizing Water Transport Through Phase-Separated Polymer Films
- 2014
-
Ingår i: Microscopy and Microanalysis. - : Oxford University Press (OUP). - 1435-8115 .- 1431-9276. ; 20:2, s. 394-406
-
Tidskriftsartikel (refereegranskat)abstract
- Drug release from oral pharmaceutical formulations can be modified by applying a polymeric coating film with controlled mass transport properties. Interaction of the coating film with water may crucially influence its composition and permeability to both water and drug. Understanding this interaction between film microstructure, wetting, and mass transport is important for the development of new coatings. We present a novel method for controlled wetting of polymer coating films in an environmental scanning electron microscope, providing direct visual information about the processes occurring as the film goes from dry to wet. Free films made of phase-separated blends of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) were used as a model system, and the blend ratio was varied to study the effect on the water transport properties. Local variations in water transport through the EC/HPC films were directly observed, enabling the immediate analysis of the structure-mass transport relationships. The leaching of HPC could be studied by evaporating water from the films in situ. Significant differences were observed between films of varying composition. The method provides a valuable complement to the current approach of making distinct diffusion and microscopy experiments for studying the dynamic interaction of polymer films with water.
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| 43. |
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| 44. |
- Jansson, Ulla-Britt, 1950, et al.
(författare)
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Voiding pattern and acquisition of bladder control from birth to age 6 years--a longitudinal study.
- 2005
-
Ingår i: The Journal of urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 174:1, s. 289-93
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We describe the voiding pattern and acquisition of bladder control in healthy children up to age 6 years. MATERIALS AND METHODS: We determined age for daytime and nighttime dryness, voiding patterns, voiding volumes and post-void residual volume per 4 hours individually and noninvasively every 3 months up to age 3 years and every 6 months up to age 6 years in 36 female and 23 male patients using 4-hour voiding observation and uroflowmetry/ultrasound. RESULTS: Median age for attaining daytime and nighttime dryness was 3.5 and 4 years, respectively. No significant difference was found between girls and boys. All but 1 child attained daytime dryness an average of 10 months before attaining nighttime dryness. Bladder sensation was reported in 31%, 79% and 100% of patients at ages 2, 3 and 4 years, respectively. Median bladder capacity was 67 ml, 123 ml and 140 ml at years 1, 3 and 6, respectively. Median post-void residual volume was 5.5 ml, 0 ml and 2 ml at ages 1, 3 and 6 years, respectively. CONCLUSIONS: Today bladder control is acquired at a later stage despite earlier awareness of bladder function. The occurrence of bladder sensation from age 1.5 years motivates an earlier start with toilet training. Infants with small post-void residual volume at age 6 months or large bladder capacity will probably attain daytime dryness earlier than those with large post-void residual volume at age 6 months or small bladder capacity.
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| 45. |
- Jansson, Ulla-Britt, 1950, et al.
(författare)
-
Voiding pattern in healthy children 0 to 3 years old: a longitudinal study.
- 2000
-
Ingår i: The Journal of urology. - 0022-5347. ; 164:6, s. 2050-4
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: We describe the development of voiding patterns and bladder control in healthy children during the first 3 years of life. MATERIALS AND METHODS: We determined voiding patterns, bladder capacity and post-void residual urine volume per 4 hours individually and noninvasively every 3 months in 36 female and 23 male healthy infants using the 4-hour voiding observation. RESULTS: Voiding frequency decreased slowly from 5 to 2 voiding episodes per 4 hours from ages 3 months to 3 years. We noted interrupted voiding in 33% of subjects at age 3 months but this condition was rare after age 2 years. Voiding during sleep occurred mainly during the first 7 months of life and did not continue after age 18 months. Bladder capacity increased from a median of 52 to 67, 68 and 123 ml. during years 1 to 3, respectively. As measured by post-void residual urine volume, bladder emptying was unchanged during years 1 and 2 but it decreased during year 3 (median 6 versus 0 and mean 4 versus 3 ml. per 4 hours). CONCLUSIONS: During the first 3 years of life the number of voiding episodes, including interrupted voiding, post-void residual urine and voiding during sleep, decreased while bladder capacity increased.
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| 46. |
- Jin, Y. K., et al.
(författare)
-
A Dual-Promoter Gene Orchestrates the Sucrose-Coordinated Synthesis of Starch and Fructan in Barley
- 2017
-
Ingår i: Molecular Plant. - : Elsevier BV. - 1674-2052 .- 1752-9867. ; 10:12, s. 1556-1570
-
Tidskriftsartikel (refereegranskat)abstract
- Sequential carbohydrate synthesis is important for plant survival because it guarantees energy supplies for growth and development during plant ontogeny and reproduction. Starch and fructan are two important carbohydrates in many flowering plants and in human diets. Understanding this coordinated starch and fructan synthesis and unraveling how plants allocate photosynthates and prioritize different carbohydrate synthesis for survival could lead to improvements to cereals in agriculture for the purposes of greater food security and production quality. Here, we report a system from a single gene in barley employing two alternative promoters, one intronic/exonic, to generate two sequence-overlapping but functionally opposing transcription factors, in sensing sucrose, potentially via sucrose/glucose/fructose/trehalose 6-phosphate signaling. The system employs an autoregulatory mechanism in perceiving a sucrose-controlled trans activity on one promoter and orchestrating the coordinated starch and fructan synthesis by competitive transcription factor binding on the other promoter. As a case in point for the physiological roles of the system, we have demonstrated that this multitasking system can be exploited in breeding barley with tailored amounts of fructan to produce healthy food ingredients. The identification of an intron/exon-spanning promoter in a hosting gene, resulting in proteins with distinct functions, adds to the complexity of plant genomes. ERYSTWYTH, WALES, V123, P453
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| 47. |
- Karlsson, Christoffer, et al.
(författare)
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Phototriggerable peptidomimetics for the inhibition of Mycobacterium turberculosis ribonucleotide reductase by targeting protein-protein binding
- 2015
-
Ingår i: Organic and biomolecular chemistry. - 1477-0520 .- 1477-0539. ; 13:9, s. 2612-2621
-
Tidskriftsartikel (refereegranskat)abstract
- Incorporation of an artificial amino acid 2 with a stilbene chromophore into peptidomimetics with three to nine amino acids yields phototriggerable candidates for inhibition of the binding between the R1 and R2 subunits of the M. tuberculosis ribonucleotide reductase (RNR). Interstrand hydrogen bond probability was used as a guideline for predicting conformational preferences of the photoisomers. Binding of these inhibitors has been rationalized by docking studies with the R1 unit. Significant differences in binding of the photoisomers were observed. For the shorter peptidomimetics, stronger binding of the Z isomer might indicate hydrophobic interactions between the stilbene chromophore and the binding site.
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| 48. |
- Kjaergaard, Magnus, et al.
(författare)
-
Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris.
- 2007
-
Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 16:9
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Tidskriftsartikel (refereegranskat)abstract
- The cysteine-rich somatomedin B domain (SMB) of the matrix protein vitronectin is involved in several important biological processes. First, it stabilizes the active conformation of the plasminogen activator inhibitor (PAI-1); second, it provides the recognition motif for cell adhesion via the cognate integrins (alpha(v)beta(3), alpha(v)beta(5), and alpha(IIb)beta(3)); and third, it binds the complex between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR). Previous structural studies on SMB have used recombinant protein expressed in Escherichia coli or SMB released from plasma-derived vitronectin by CNBr cleavage. However, different disulfide patterns and three-dimensional structures for SMB were reported. In the present study, we have expressed recombinant human SMB by two different eukaryotic expression systems, Pichia pastoris and Drosophila melanogaster S2-cells, both yielding structurally and functionally homogeneous protein preparations. Importantly, the entire population of our purified, recombinant SMB has a solvent exposure, both as a free domain and in complex with PAI-1, which is indistinguishable from that of plasma-derived SMB as assessed by amide hydrogen ((1)H/(2)H) exchange. This solvent exposure was only reproduced by one of three synthetic SMB products with predefined disulfide connectivities corresponding to those published previously. Furthermore, this connectivity was also the only one to yield a folded and functional domain. The NMR structure was determined for free SMB produced by Pichia and is largely consistent with that solved by X-ray crystallography for SMB in complex with PAI-1.
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| 49. |
- Li, Wei, 1962-, et al.
(författare)
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Foam cell death induced by 7β-hydroxycholesterol is mediated by labile iron-driven oxidative injury : Mechanisms underlying induction of ferritin in human atheroma
- 2005
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Ingår i: Free Radical Biology & Medicine. - : Elsevier BV. - 0891-5849 .- 1873-4596. ; 39:7, s. 864-875
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Tidskriftsartikel (refereegranskat)abstract
- Human atherosclerotic lesions typically contain large amounts of ferritin associated with apoptotic macrophages and foam cells, although the reasons are unknown. In the present investigation, we studied the relationship between ferritin induction and occurrence of apoptosis in 7β-hydroxycholesterol (7β-OH)-treated monocytic cells and macrophages. We found that 7β-OH enlarges the intracellular labile iron pool, increases formation of reactive oxygen species (ROS), and induces ferritin and cytosolic accumulation of lipid droplets, lysosomal destabilization, and apoptototic macrophage death. Since ferritin is a phase II-type protective protein, our findings suggest that ferritin upregulation here worked as an inefficient defense mechanism. Addition to the culture medium of both a membrane-permeable iron chelator 10-phenanthroline and the non-membrane-permeable iron chelators apoferritin and desferrioxamine afforded significant protection against the 7β-OH-induced effects. Consequently, endocytosed iron compounds dramatically augmented 7β-OH-induced cytotoxicity. We conclude that oxidized lipid 7β-OH causes not only foam cell formation but also oxidative damage with abnormal metabolism of cellular iron. The findings suggest that modulation of iron metabolism in human atheroma may be a potential therapeutic strategy against atherosclerosis. © 2005 Elsevier Inc. All rights reserved.
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| 50. |
- Mao, Fang, et al.
(författare)
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Combinatorial Study of Gradient Ag-Al Thin Films : Microstructure, Phase Formation, Mechanical and Electrical Properties
- 2016
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 8:44, s. 30635-30643
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Tidskriftsartikel (refereegranskat)abstract
- A combinatorial approach is applied to rapidly deposit and screen Ag-Al thin films-to evaluate the mechanical, tribological, and electrical properties as a function of chemical composition. Ag-Al thin films with large continuous composition gradients (6-60 atom % Al) were deposited by a custom-designed combinatorial magnetron sputtering system. X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX), scanning and transmission electron microscopy (SEM and TEM), X-ray photoelectron spectroscopy (XPS), nanoindentation, and four-point electrical resistance screening were employed to characterize the chemical composition, structure, and physical properties of the films in a time-efficient way. For low Al contents (<13 atom %), a highly (111)-textured fcc phase was formed. At higher Al contents, a (002)-textured hcp solid solution phase was formed followed by a fcc phase in the most At-rich regions. No indication of a mu phase was observed. The Ag-Al films with fcc-Ag matrix is prone to adhesive material transfer leading to a high friction coefficient (>1) and adhesive wear, similar to the behavior of pure Ag. In contrast, the hexagonal solid solution phase (from ca. 15 atom %Al) exhibited dramatically reduced friction coefficients (about 15% of that of the fcc phase) and dramatically reduced adhesive wear when tested against the pure Ag counter surface. The increase in contact resistance of the Ag Al films is limited to only 50% higher than a pure Ag reference sample at the low friction and low wear region (19-27 atom %). This suggests that a hcp Ag Al alloy can have a potential use in sliding electrical contact applications and in the future will replace pure Ag in specific electromechanical applications.
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