| 1. |
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| 2. |
- Kattge, Jens, et al.
(author)
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TRY plant trait database - enhanced coverage and open access
- 2020
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In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
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Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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| 3. |
- Khatri, B., et al.
(author)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 4. |
- Baldsiefen, G, et al.
(author)
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Shears bands in Pb-193
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 54:3, s. 1106-1116
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Journal article (peer-reviewed)abstract
- Four bands of enhanced dipole transitions, with weak crossovers, have been observed in Pb-195. Three of these bands are connected to the spherical levels. in addition, the spherical level scheme has been extended. The nuclear spectroscopy was done with the early implementation of GAMMASPHERE and HERA arrays of Get detectors. The nucleus Pb-193 was populated in the Yb-174(Mg-24,5n) reaction at beam energies of 129, 131, and 134 MeV. The experimental results are compared to tilted-axis cranking calculations. The systematical behavior of the dipole bands in the heavier odd-A Pb isotopes, Pb-195,Pb-197,Pb-199,Pb-201, is also discussed.
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| 5. |
- Brinkman, M J, et al.
(author)
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Decay from a superdeformed band in Pb-194
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:4, s. R1461-R1464
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Journal article (peer-reviewed)abstract
- Three experiments using the (174) Yb(Mg-25,5n)Pb-194 reaction have been undertaken at the Early Implementation of Gammasphere to study the decay of known superdeformed states in Pb-194. A single discrete transition with an energy of 2.746(2) MeV carrying 6(2)% of the full superdeformed band intensity has been identified. A discussion of our results and the assignment of the 2.746-MeV transition as a discrete gamma ray directly connecting the superdeformed 8(+) and low-lying 6(+) levels will be presented.
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| 6. |
- Zaidi, Syed H., et al.
(author)
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Landscape of somatic single nucleotide variants and indels in colorectal cancer and impact on survival
- 2020
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a biologically heterogeneous disease. To characterize its mutational profile, we conduct targeted sequencing of 205 genes for 2,105 CRC cases with survival data. Our data shows several findings in addition to enhancing the existing knowledge of CRC. We identify PRKCI, SPZ1, MUTYH, MAP2K4, FETUB, and TGFBR2 as additional genes significantly mutated in CRC. We find that among hypermutated tumors, an increased mutation burden is associated with improved CRC-specific survival (HR=0.42, 95% CI: 0.21-0.82). Mutations in TP53 are associated with poorer CRC-specific survival, which is most pronounced in cases carrying TP53 mutations with predicted 0% transcriptional activity (HR=1.53, 95% CI: 1.21-1.94). Furthermore, we observe differences in mutational frequency of several genes and pathways by tumor location, stage, and sex. Overall, this large study provides deep insights into somatic mutations in CRC, and their potential relationships with survival and tumor features. Large scale sequencing study is of paramount importance to unravel the heterogeneity of colorectal cancer. Here, the authors sequenced 205 cancer genes in more than 2000 tumours and identified additional mutated driver genes, determined that mutational burden and specific mutations in TP53 are associated with survival odds.
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| 7. |
- Clark, R M, et al.
(author)
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Superdeformation in bismuth
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:1, s. 117-123
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Journal article (peer-reviewed)abstract
- High angular momentum states in Bi-195-197 are populated in two reactions: W-183(F-19,xn)Bi-202-x and Ta-181(Ne-20,xn)Bi-201-x at beam energies of 108 and 123 MeV, respectively. Gamma rays were detected using the Gammasphere array. Three weakly populated rotational sequences have been found. They each have properties characteristic of other superdeformed bands in this mass region. On the basis of cross-bombardment information we believe that one band belongs to each of Bi-195, Bi-196, and Bi-197. The properties of the bands in the odd-Bi nuclei are best reproduced if the odd proton occupies the favored signature of the [651]1/2 orbital, while the band in Bi-196 has this same proton configuration coupled to an additional N=7 (j(15/2)) neutron. The relative behavior of the J((2)) moments of inertia can be qualitatively understood in terms of Pauli-blocking effects.
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| 8. |
- McNabb, D P, et al.
(author)
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Superdeformation in Po-198
- 1996
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 53:2, s. R541-R543
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Journal article (peer-reviewed)abstract
- The Yb-174(Si-29,5n) reaction at 148 MeV with thin targets was used to populate high-angular momentum states in Po-198. Resulting gamma rays were observed with Gammasphere. A weakly populated superdeformed band of 10 gamma-ray transitions was found and has been assigned to Po-198. This is the first observation of an SD band in the A approximate to 190 region in a nucleus with Z > 83. The J((2))) of the new band is very similar to those of the yrast SD bands in Hg-194 and Pb-196. The intensity profile suggests that this band is populated through states close to where the SD band crosses the yrast line and the angular momentum at which the fission process dominates.
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| 9. |
- Brito-Zeron, P., et al.
(author)
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Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
- 2023
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2448-2457
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Journal article (peer-reviewed)abstract
- ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
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| 10. |
- Flores-Chavez, A., et al.
(author)
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Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
- 2023
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2437-2447
-
Journal article (peer-reviewed)abstract
- Objective To analyse how the key components at the time of diagnosis of the Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. Methods For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. Results After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. Conclusion Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjogren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
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| 11. |
- Lessard, Christopher J., et al.
(author)
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Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome
- 2013
-
In: Nature Genetics. - : NATURE PUBLISHING GROUP, 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA. - 1061-4036 .- 1546-1718. ; 45:11, s. 1284-
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Journal article (peer-reviewed)abstract
- Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome.
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| 12. |
- Clark, R M, et al.
(author)
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Relative deformations of superdeformed bands in Ce-131,Ce-132
- 1996
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 76:19, s. 3510-3513
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Journal article (peer-reviewed)abstract
- The quadrupole moments Q(0) of five superdeformed bands in Ce-131,Ce-132 have been established using the Doppler-shift attenuation method; for the first time, we can compare relative deformations of yrast and excited bands in different nuclei to an accuracy of similar or equal to(5-7)%. Four of the five bands have very similar deformations, while the excited band in Ce-131 has a somewhat larger quadrupole moment. Important new information is presented on the shape-driving force of the vi(13/2) orbital, the stability of the second minimum with respect to particle excitations, the relative deformations of identical bands, the nature of the sidefeeding, and the time scale of the decay process.
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| 13. |
- Joss, D T, et al.
(author)
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Lifetime measurements of a triaxial band in Ce-133
- 1998
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In: Acta Physica Hungarica A. - 1219-7580 .- 1588-2675. ; 7:1, s. 111-112
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Journal article (peer-reviewed)abstract
- The Doppler shift attenuation method has been used to determine the transition quadrupole moment of a triaxial band belonging to the gamma-soft nucleus, Ce-133. Doppler broadened lineshape (DBLS) analysis has revealed the magnitude of the Q(t) value to be similar to 2.4 eb. This contribution provides new information of (i) the transition quadrupole moment of this band (ii) the lifetimes of in-band and sidefeeding transitions and (iii) the relative deformations of coexisting nuclear shapes.
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| 14. |
- Joss, D T, et al.
(author)
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Lifetime measurements of a triaxial band in Ce-133
- 1998
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 58:6, s. 3219-3222
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Journal article (peer-reviewed)abstract
- Lifetimes of states within a triaxial band belonging to;the gamma-soft nucleus Ce-133 have been determined through a Doppler-broadened line shape analysis. A value, Q(t)approximate to 2.2 eb, has been found for the transition quadrupole moment which is considerably smaller than that of superdeformed structures (Q(t)approximate to 7.4 e b) in this mass region. The results are discussed in terms of deformation self-consistent calculations based on the total Routhian surface formalism. [S0556-2813(98)01912-8].
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| 15. |
- Li, He, et al.
(author)
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Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons
- 2017
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In: PLOS Genetics. - : PUBLIC LIBRARY SCIENCE. - 1553-7390 .- 1553-7404. ; 13:6
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Journal article (peer-reviewed)abstract
- Sjogren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 x 10(-14)). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (P-meta = 2.59 x 10(-9); odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.
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| 16. |
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| 17. |
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| 18. |
- Klamra, Wlodzimierz, et al.
(author)
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High-spin multiparticle-hole excitations in Eu-148
- 2001
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In: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-6001 .- 1434-601X. ; 10:1, s. 11-12
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Journal article (peer-reviewed)abstract
- Studies by means of 155 MeV Al-27 bombardment on a Te-130 target revealed in Eu-148 high-spin structures up to spin 31 (n) over tilde, in addition to a cascade extended to the 11088.1 keV excitation. The observed levels are tentatively assigned as complex multiparticle-hole proton and neutron configurations.
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| 19. |
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| 20. |
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| 21. |
- BERNSTEIN, LA, et al.
(author)
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ONSET OF COLLECTIVITY IN NEUTRON-DEFICIENT PO-196,PO-198
- 1995
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 52:2, s. 621-627
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Journal article (peer-reviewed)abstract
- We have studied via in-beam gamma-ray spectroscopy Po-196 and Po-198, which are the first neutron-deficient Po isotopes to exhibit a collective low-lying structure. The ratios of yrast state energies and the E2 branching ratios of transitions from non-yrast to yrast states are indicative of a low-lying vibrational structure. The onset of collective motion in these isotopes can be attributed to the opening of the neutron i(13/2) orbital at N approximate to 112 and the resulting large overlap between the two valence protons in the h(9/2) orbital and the valence neutrons in the i(13/2) orbital.
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| 22. |
- Borozan, Ivan, et al.
(author)
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Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis
- 2022
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:1, s. 210-220
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Journal article (peer-reviewed)abstract
- Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis.Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations.Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations.Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes.
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| 23. |
- Cozzolino, C. A., et al.
(author)
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Exploiting the nano-sized features of microfibrillated cellulose (MFC) for the development of controlled-release packaging
- 2013
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In: Colloids and Surfaces B. - : Elsevier BV. - 0927-7765 .- 1873-4367. ; 110, s. 208-216
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Journal article (peer-reviewed)abstract
- Microfibrillated cellulose (MFC) was used in this study to prepare films containing an active molecule, lysozyme, which is a natural antimicrobial agent. The main goal of this research was to assess the potential for exploiting the nano-sized dimension of cellulose fibrils to slow the release of the antimicrobial molecule, thus avoiding a too-quick release into the surrounding medium, which is a major disadvantage of most release systems. For this purpose, the release kinetics of lysozyme over a 10-day period in two different media (pure water and water/ethanol 10. wt.%) were obtained, and the experimental data was fitted with a solution of Fick's second law to quantify the apparent diffusion coefficient (D). The results indicate that the MFC retained lysozyme, presumably due to electrostatic, hydrogen, and ion-dipole interactions, with the largest release of lysozyme-approximately 14%-occurring from the initial amount loaded on the films. As expected, ethanol as a co-solvent slightly decreased the diffusion of lysozyme from the MFC polymer network. The addition of two potential modulating release agents-glycerol and sodium chloride-was also evaluated. Findings from this work suggest that MFC-based films can be considered a suitable candidate for use in controlled-release packaging systems.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Khatri, B, et al.
(author)
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GENOME-WIDE ASSOCIATION STUDY OF SJOGREN'S SYNDROME IDENTIFIES TEN NEW RISK LOCI
- 2020
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 79, s. 30-31
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Conference paper (other academic/artistic)abstract
- Sjögren’s syndrome (SS) is a complex autoimmune disease with exocrine gland dysfunction leading to substantial morbidity. There are 10 published genetic susceptibility loci.Objectives:Our genome-wide association study (GWAS) aimed to identify additional risk loci of genome-wide significance (GWS; p<5E-08) in European-derived primary SS.Methods:A total of 3232 cases and 17481 controls genotyped on GWAS arrays and 619 cases and 6171 controls genotyped on ImmunoChip (IC) arrays were imputed after quality control. Logistic regression was calculated adjusting for ancestry using the first 4 principal components to identify SS-associated SNPs. GWAS and IC results were meta-analyzed using weighted Z-scores. Bayesian statistics were used to assign posterior probabilities and define credible SNP sets for each locus. Bioinformatic analyses were used to predict functionality.Results:Seven novel loci exceeded GWS in the GWAS analysis:NAB1,MIR146A-PTTG1,XKR6,MAPT-CRHR1,RPTOR-CHMP6-BAIAP2,TYK2andSYNGR1. Meta-analysis with IC data identified three more novel loci exceeding GWS:CD247,PRDM1-ATG5andTNFAIP3. Several additional loci with suggestive association (p<1E-05) were also identified:ADAMTSL2,CGNL1andPHRF1.Several identified loci have reported functional implications in immune regulation and autoimmune disease. In lupus, rs2431697 correlated with rs2431098, which was shown to alterMIR146Aexpression, resulting in type I interferon pathway imbalance. Similarly,TYK2risk association reportedly drives interferon, IL10 and RET signaling pathways.PRDM1encodes Blimp-1, a master regulator of immune cell differentiation.CD247encodes the zeta subunit of the T cell receptor complex.XKR6is implicated in apoptotic cell ingestion.ATG5is also involved in apoptosis, as well as autophagy and antigen presentation.Additional bioinformatics analyses (Haploreg, Regulome DB, ENCODE, etc.) revealed immune-relevant functional implications for each risk locus. The SS-associated credible set included variants downstream ofTNFAIP3in a region reported to abolish looping between an enhancer and theTNFAIP3promoter in lupus and a coding variant that has been shown to alter NF-kB activity and neutrophil extra-cellular traps. The rs2293765 in the 5’ UTR ofNAB1showed evidence of enhancer/promoter activities. The rs2069235 in theSYNGR1locus showed enhancer and transcription start site activities in B and T cells. The rs7210219 in theMAPT-CRHR1locus showed enhancer/promotor activities in various tissues.Conclusion:We have identified ten novel genetic susceptibility loci associated with SS pathology. Our finding increases the current number of GWS regions in SS patients of European origin, from 10 to 20. Future work is needed to identify and characterize the functional variants in each region.Disclosure of Interests:Bhuwan Khatri: None declared, Tove Ragna Reksten: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen Speakers bureau: Novartis, ThermoFischer, R Hal Scofield Grant/research support from: Pfizer, Simon J. Bowman Consultant of: Astrazeneca, Biogen, BMS, Celgene, Medimmune, MTPharma, Novartis, Ono, UCB, xtlbio, Glapagos, Speakers bureau: Novartis, Joel Guthridge Grant/research support from: Xencor, Bristol Myers Squibb, DXterity, Judith A. James Grant/research support from: Progentec Diagnostics, Inc, Consultant of: Abbvie, Novartis, Jannsen, Lars Ronnblom Grant/research support from: AZ, Speakers bureau: AZ, Blake M Warner: None declared, Xavier Mariette: None declared, Roald Omdal: None declared, Javier Martin Ibanez: None declared, Maria Teruel: None declared, Janicke Liaaen Jensen: None declared, Lara A Aqrawi: None declared, Øyvind Palm: None declared, Marie Wahren-Herlenius: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, A Darise Farris Speakers bureau: Biogen, Marta Alarcon-Riquelme: None declared, Wan-fai Ng: None declared, Kathy L Sivils: None declared, Gunnel Nordmark: None declared, Christopher Lessard: None declared
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| 28. |
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| 29. |
- Aghakhanian, F, et al.
(author)
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INTEGRATION OF GWAS AND EPIGENETIC STUDIES IDENTIFIES NOVEL GENES THAT ALTER EXPRESSION IN THE MINOR SALIVARY GLAND IN SJOGREN'S DISEASE
- 2022
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 72-73
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Conference paper (other academic/artistic)abstract
- Sjogren’s disease (SjD) is an autoimmune disease characterized by reduced function of exocrine glands (i.e., salivary and lacrimal glands). Epithelial cell damage resulting from lymphocytic infiltration has been implicated in SjD etiology [1]. How genetic and epigenetic changes influence epithelial-immune cell interactions in SjD pathogenesis remain understudied.ObjectivesEvaluate the role of SjD risk loci in salivary gland tissue to gain insights into the potential genes involved in salivary gland dysfunction.MethodsSNPs from 16 regions with SNP-SjD associations (P<5x10-8) in our GWAS study (3232 SjD cases) and meta-analysis of ImmunoChip data (619 SjD cases) [2] were interrogated for eQTLs using Genotype-Tissue Expression (GTEx) minor salivary gland data. Subsequent analysis identified genes that were both eQTLs in the minor salivary gland and significantly expressed in RNA-seq and ATAC-seq data from the submaxillary salivary gland epithelial cell line, A253. Pathway enrichment analysis was performed using gProfiler on the genes where coalescence of eQTL, RNA-seq, and ATAC-seq data was observed. To further validate the results, we performed transcriptome-wide association study (TWAS) analysis using GWAS summary statistics and minor salivary gland eQTL GTEx data.ResultsIn total, 5884 genome-wide significant SNPs from 16 SjD risk loci were identified as potential minor salivary gland eQTLs using two discovery thresholds: p(FDR)<0.05 provided by eQTL study (3566 SNPs) and p(FDR)>0.05 and p<0.05 in eQTL study (2318 SNPs). Further analysis revealed 10 SjD risk loci with SNPs that were minor salivary gland eQTLs for a total of 155 unique genes that had a coalescence of RNA- and ATAC-seq data in A253 cells. Many SNPs altered the expression of the nearest gene to the risk allele (i.e., index gene), such as IRF5 and TNPO3 on chromosome 7 at 128Mb; however, this locus had 12 additional genes that were eQTLs in minor salivary gland. In contrast, other loci had no reported eQTLs for the index gene, but several reported eQTLs for other genes, such TYK2 on chromosome 19 at 10Mb that showed no change in TYK2 expression but eQTLs for 8 distant genes, including ICAM1. Pathway enrichment analysis revealed an enrichment in Butyrophilin (BTN) family interactions (R-HSA-8851) (PAdj=1.564x10-5), including the BTN2A1, BTN2A2, BTN3A1, BTN3A2 and BTN3A3 gene cluster in the MHC region. In further support, TWAS of the minor salivary gland and the SjD GWAS summary statistics (after Bonferroni correction) showed association between SjD and BTN3A2 (p=1.24x10-42), as well as many other loci in the MHC region. In addition, several long non-coding (lnc) RNAs on chromosome 17 were significant, peaking at RP11-259G18.1 (p=4.43x10-10).ConclusionThis study shows that SjD-associated risk alleles influence disease by altering gene expression in immune cells and minor salivary glands. Further, our analysis suggests that altered gene expression in the minor salivary gland expands beyond effects on the index gene to several genes on each locus. Interestingly, we observed minor salivary gland eQTLs for several BTN family genes, which act as cell-surface binding partners to regulate cell-cell interactions, including interactions between epithelial cells and activated T cells [3]. Future work will assess chromatin-chromatin-interactions within the 10 SjD risk loci in salivary gland cells and tissues to map local chromatin regulatory networks that regulate gene expression. Additional transcriptional studies of SjD minor salivary gland tissues will provide further insights into how altered gene expression in the salivary gland influences SjD pathology.References[1]Verstappen. Nat Rev Rheumatol 2021;17(6):333-348.[2]Khatri, et al. Annals of Rheumatic Diseases 2020;79:30-31.[3]Arnett HA, Viney JL. Nature Reviews Immunology 2014;14:559-569.Disclosure of InterestsFarhang Aghakhanian: None declared, Mandi M Wiley: None declared, Bhuwan Khatri: None declared, Kandice L Tessneer: None declared, Astrid Rasmussen: None declared, Simon J. Bowman Consultant of: Abbvie, Galapagos, and Novartis in 2020-2021., Lida Radfar: None declared, Roald Omdal: None declared, Marie Wahren-Herlenius: None declared, Blake M Warner: None declared, Torsten Witte: None declared, Roland Jonsson: None declared, Maureen Rischmueller: None declared, Patrick M Gaffney: None declared, Judith A. James: None declared, Lars Ronnblom: None declared, R Hal Scofield: None declared, Xavier Mariette: None declared, Marta Alarcon-Riquelme: None declared, Wan Fai Ng: None declared, Kathy Sivils Employee of: Current employee of Janssen, Gunnel Nordmark: None declared, Umesh Deshmukh: None declared, A Darise Farris: None declared, Christopher Lessard: None declared
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| 30. |
- Brito-Zerón, Pilar, et al.
(author)
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Mortality risk factors in primary Sjögren syndrome : a real-world, retrospective, cohort study
- 2023
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In: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 61
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Journal article (peer-reviewed)abstract
- BackgroundWhat baseline predictors would be involved in mortality in people with primary Sjögren syndrome (SjS) remains uncertain. This study aimed to investigate the baseline characteristics collected at the time of diagnosis of SjS associated with mortality and to identify mortality risk factors for all-cause death and deaths related to systemic SjS activity measured by the ESSDAI score.MethodsIn this international, real-world, retrospective, cohort study, we retrospectively collected data from 27 countries on mortality and causes of death from the Big Data Sjögren Registry. Inclusion criteria consisted of fulfilling 2002/2016 SjS classification criteria, and exclusion criteria included chronic HCV/HIV infections and associated systemic autoimmune diseases. A statistical approach based on a directed acyclic graph was used, with all-cause and Sjögren-related mortality as primary endpoints. The key determinants that defined the disease phenotype at diagnosis (glandular, systemic, and immunological) were analysed as independent variables.FindingsBetween January 1st, 2014 and December 31, 2023, data from 11,372 patients with primary SjS (93.5% women, 78.4% classified as White, mean age at diagnosis of 51.1 years) included in the Registry were analysed. 876 (7.7%) deaths were recorded after a mean follow-up of 8.6 years (SD 7.12). Univariate analysis of prognostic factors for all-cause death identified eight Sjögren-related variables (ocular and oral tests, salivary biopsy, ESSDAI, ANA, anti-Ro, anti-La, and cryoglobulins). The multivariate CPH model adjusted for these variables and the epidemiological features showed that DAS-ESSDAI (high vs no high: HR = 1.68; 95% CI, 1.27–2.22) and cryoglobulins (positive vs negative: HR = 1.72; 95% CI, 1.22–2.42) were independent predictors of all-cause death. Of the 640 deaths with available information detailing the specific cause of death, 14% were due to systemic SjS. Univariate analysis of prognostic factors for Sjögren-cause death identified five Sjögren-related variables (oral tests, clinESSDAI, DAS-ESSDAI, ANA, and cryoglobulins). The multivariate competing risks CPH model adjusted for these variables and the epidemiological features showed that oral tests (abnormal vs normal results: HR = 1.38; 95% CI, 1.01–1.87), DAS-ESSDAI (high vs no high: HR = 1.55; 95% CI, 1.22–1.96) and cryoglobulins (positive vs negative: HR = 1.52; 95% CI, 1.16–2) were independent predictors of SjS-related death.InterpretationThe key mortality risk factors at the time of SjS diagnosis were positive cryoglobulins and a high systemic activity scored using the ESSDAI, conferring a 2-times increased risk of all-cause and SjS-related death. ESSDAI measurement and cryoglobulin testing should be considered mandatory when an individual is diagnosed with SjS.
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| 31. |
- Cederwall, Bo, et al.
(author)
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PROPERTIES OF SUPERDEFORMED BANDS IN DY-153
- 1995
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 346:3-4, s. 244-250
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Journal article (peer-reviewed)abstract
- Two new superdeformed (SD) bands in Dy-153, in addition to the three previously observed, have been studied with the GAMMASPHERE detector array. Assignments to single-neutron orbits in the SD potential are made based on the band properties. Evidence for a band interaction at very high spins, possibly involving the first N = 7 proton intruder orbital, is observed in the strongest populated SD band. Furthermore, evidence far a Delta I = 2 staggering is also found in this SD band.
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| 32. |
- Cozzolino, Carlo A., et al.
(author)
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Dye release behavior from polyvinyl alcohol films in a hydro-alcoholic medium : Influence of physicochemical heterogeneity
- 2012
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In: Colloids and Surfaces A. - : Elsevier BV. - 0927-7757 .- 1873-4359. ; 403, s. 45-53
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Journal article (peer-reviewed)abstract
- In this paper we investigated the release kinetics of a model drug-like compound (Coomassie brilliant blue) from polyvinyl alcohol (PVOH) films into a hydro-alcoholic solution as a function of the physicochemical properties of the polymer matrix. After 33 days of monitoring, the total amount released ranged from 10% for the high hydrolysis degree/low molecular weight PVOH films to 60% for the low hydrolysis degree/low molecular weight films. Mathematical modeling allowed for an estimation of the two diffusion coefficients (D 1 and D 2) that characterized the release profile of the dye from the films. The degree of hydrolysis dramatically affected both the morphology and the physical structure of the polymer network. A high hydroxyl group content was also associated with the shifting of second order and first order transitions toward higher temperatures, with a concurrent increase in crystallinity. Moreover, the higher the degree of hydrolysis, the higher the affinity of the polymer to the negatively charged molecule dye. Selection of the polymer matrix based on physicochemical criteria may help in achieving different release patterns, thereby representing the first step for the production of polymer systems with modulated release properties.
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| 33. |
- Cozzolino, Carlo A., et al.
(author)
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Microfibrillated cellulose and borax as mechanical, O-2-barrier, and surface-modulating agents of pullulan biocomposite coatings on BOPP
- 2016
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In: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 143, s. 179-187
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Journal article (peer-reviewed)abstract
- Multifunctional composite coatings on bi-oriented polypropylene (BOPP) films were obtained using borax and microfibrillated cellulose (MFC) added to the main pullulan coating polymer. Spectroscopy analyses suggested that a first type of interaction occurred via hydrogen bonding between the C-6-OH group of pullulan and the hydroxyl groups of boric acid, while monodiol and didiol complexation represented a second mechanism. The deposition of the coatings yielded an increase in the elastic modulus of the entire plastic substrate (from similar to 2 GPa of the neat BOPP to similar to 3.1 GPa of the P/B+/MFC-coated BOPP). The addition of MFC yielded a decrease of both static and kinetic coefficients of friction of approximately 22% and 25%, respectively, as compared to the neat BOPP. All composite coatings dramatically increased the oxygen barrier performance of BOPP, especially under dry conditions. The deposition of the high hydrophilic coatings allowed to obtain highly wettable surfaces (water contact angle of similar to 18 degrees).
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| 34. |
- Goloboff, P., Farris, S., Källersjö, M., Oxelman. B., Ramirez, M. J., Szumik, C. A.
(author)
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Improvements to resampling measures of group support
- 2003
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In: Cladistics. ; 19, s. 324-332
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Journal article (peer-reviewed)
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| 35. |
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| 36. |
- Kim, Minji, et al.
(author)
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Decreased catalytic activity of the insulin-degrading enzyme in chromosome 10-linked Alzheimer disease families
- 2007
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In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 282:11, s. 7825-7832
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Journal article (peer-reviewed)abstract
- Insulin-degrading enzyme (IDE) is a zinc metalloprotease that degrades the amyloid beta-peptide, the key component of Alzheimer disease (AD)-associated senile plaques. We have previously reported evidence for genetic linkage and association of AD on chromosome 10q23-24 in the region harboring the IDE gene. Here we have presented the first functional assessment of IDE in AD families showing the strongest evidence of the genetic linkage. We have examined the catalytic activity and expression of IDE in lymphoblast samples from 12 affected and unaffected members of three chromosome 10-linked AD pedigrees in the National Institute of Mental Health AD Genetics Initiative family sample. We have shown that the catalytic activity of cytosolic IDE to degrade insulin is reduced in affected versus unaffected subjects of these families. Further, we have shown the decrease in activity is not due to reduced IDE expression, suggesting the possible defects in IDE function in these AD families. In attempts to find potential mutations in the IDE gene in these families, we have found no coding region substitutions or alterations in splicing of the canonical exons and exon 15b of IDE. We have also found that total IDE mRNA levels are not significantly different in sporadic AD versus age-matched control brains. Collectively, our data suggest that the genetic linkage of AD in this set of chromosome 10-linked AD families may be the result of systemic defects in IDE activity in the absence of altered IDE expression, further supporting a role for IDE in AD pathogenesis.
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| 37. |
- Knoop, Florian, et al.
(author)
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TDEP:Temperature Dependent Effective Potentials
- 2024
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In: Journal of Open Source Software. - : Open journals. - 2475-9066. ; 9:94
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Journal article (peer-reviewed)abstract
- The Temperature Dependent Effective Potential (TDEP) method is a versatile and efficient approach to include temperature in a binitio materials simulations based on phonon theory. TDEP can be used to describe thermodynamic properties in classical and quantum ensembles, and several response properties ranging from thermal transport to Neutron and Raman spectroscopy. A stable and fast reference implementation is given in the software package of the same name described here. The underlying theoretical framework and foundation is briefly sketched with an emphasis on discerning the conceptual difference between bare and effective phonon theory, in both self-consistent and non-self-consistent formulations. References to numerous applications and more in-depth discussions of the theory are given.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
- Rovera, C., et al.
(author)
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Mechanical behavior of biopolymer composite coatings on plastic films by depth-sensing indentation – A nanoscale study
- 2018
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In: Journal of Colloid and Interface Science. - : Academic Press. - 0021-9797 .- 1095-7103. ; 512, s. 638-646
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Journal article (peer-reviewed)abstract
- Fundamental physical behaviors of materials at the nanoscale level are crucial when local aspects govern the macroscale performance of nanocomposites, e.g., interface and surface phenomena. Because of the increasing interest in biopolymer nanocomposite coatings for many different applications (e.g., optical devices, displays/screens, and packaging), this work investigates the potential of nanoindentation as a method for clarifying the interplay between distinct phases (i.e., organic and inorganic) at local level in thin biopolymer films loaded with nanoparticles. The nanomechanical features of pullulan nanocomposite coatings laid on polyethylene terephthalate (PET) were quantified in terms of elastic modulus (E), hardness (H), and creep (C) through an instrumented indentation test composed of a loading-holding-unloading cycle. Colloidal silica (CS) and cellulose nanocrystals (CNCs) were used as spherical and rod-like nanoparticles, respectively. An overall reinforcing effect was shown for all nanocomposite coatings over the pristine (unfilled) pullulan coating. A size effect was also disclosed for the CS-loaded surfaces, with the highest E value recorded for the largest particles (8.19 ± 0.35 GPa) and the highest H value belonging to the smallest ones (395.41 ± 25.22 MPa). Comparing CS and CNCs, the addition of spherical nanoparticles had a greater effect on the surface hardness than cellulose nanowhiskers (353.50 ± 83.52 MPa and 321.36 ± 43.26 MPa, respectively). As for the elastic modulus, the addition of CS did not provide any improvement over both the bare and CNC-loaded pullulan coatings, whereas the coating including CNCs exhibited higher E values (p <. 05). Finally, CS-loaded pullulan coatings were the best performing in terms of C properties, with an average indentation depth of 16.5 ± 1.85 nm under a load of ∼190 μN. These results are discussed in terms of local distribution gradients, surface chemistry of nanoparticles, and how nanoparticle aggregation occurred in the dry nanocomposite coatings.
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| 42. |
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