| 151. |
- Salamanova, Evdokiya, et al.
(författare)
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A subset of functional adaptation mutations alter propensity for alpha-helical conformation in the intrinsically disordered glucocorticoid receptor taulcore activation domain
- 2018
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Ingår i: Biochimica et Biophysica Acta - General Subjects. - : ELSEVIER SCIENCE BV. - 0304-4165 .- 1872-8006. ; 1862:6, s. 1452-1461
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adaptive mutations that alter protein functionality are enriched within intrinsically disordered protein regions (IDRs), thus conformational flexibility correlates with evolvability. Pre-structured motifs (PreSMos) with transient propensity for secondary structure conformation are believed to be important for IDR function. The glucocorticoid receptor taulcore transcriptional activation domain (GR taulcore) domain contains three a-helical PreSMos in physiological buffer conditions.Methods: Sixty change-of-function mutants affecting the intrinsically disordered 58-residue GR taulcore were studied using disorder prediction and molecular dynamics simulations.Results: Change-of-function mutations were partitioned into seven clusters based on their effect on IDR predictions and gene activation activity. Some mutations selected from clusters characterized by mutations altering the IDR prediction score, altered the apparent stability of the a-helical form of one of the PreSMos in molecular dynamics simulations, suggesting PreSMo stabilization or destabilization as strategies for functional adaptation. Indeed all tested gain-of-function mutations affecting this PreSMo were associated with increased stability of the a-helical PreSMo conformation, suggesting that PreSMo stabilization may be the main mechanism by which adaptive mutations can increase the activity of this IDR type. Some mutations did not appear to affect PreSMo stability.Conclusions: Changes in PreSMo stability account for the effects of a subset of change-of-function mutants affecting the GR taulcore IDR. General significance: Long IDRs occur in about 50% of human proteins. They are poorly characterized despite much recent attention. Our results suggest the importance of a subtle balance between PreSMo stability and IDR activity, which may provide a novel target for future pharmaceutical intervention.
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| 152. |
- Samudyata, Samudyata, et al.
(författare)
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Interaction of Sox2 with RNA binding proteins in mouse embryonic stem cells
- 2019
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Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 381:1, s. 129-138
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Tidskriftsartikel (refereegranskat)abstract
- Sox2 is a master transcriptional regulator of embryonic development. In this study, we determined the protein interactome of Sox2 in the chromatin and nucleoplasm of mouse embryonic stem (mES) cells. Apart from canonical interactions with pluripotency-regulating transcription factors, we identified interactions with several chromatin modulators, including members of the heterochromatin protein 1 (HP1) family, suggesting a role for Sox2 in chromatin-mediated transcriptional repression. Sox2 was also found to interact with RNA binding proteins (RBPs), including proteins involved in RNA processing. RNA immunoprecipitation followed by sequencing revealed that Sox2 associates with different messenger RNAs, as well as small nucleolar RNA Snord34 and the non-coding RNA 7SK. 7SK has been shown to regulate transcription at gene regulatory regions, which could suggest a functional interaction with Sox2 for chromatin recruitment. Nevertheless, we found no evidence of Sox2 modulating recruitment of 7SK to chromatin when examining 7SK chromatin occupancy by Chromatin Isolation by RNA Purification (ChIRP) in Sox2 depleted mES cells. In addition, knockdown of 7SK in mES cells did not lead to any change in Sox2 occupancy at 7SK-regulated genes. Thus, our results show that Sox2 extensively interacts with RBPs, and suggest that Sox2 and 7SK co-exist in a ribonucleoprotein complex whose function is not to regulate chromatin recruitment, but could rather regulate other processes in the nucleoplasm.
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| 153. |
- Shoukry, Yasser, et al.
(författare)
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SMT-Based Observer Design for Cyber-Physical Systems under Sensor Attacks
- 2016
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Ingår i: 2016 ACM/IEEE 7th International Conference on Cyber-Physical Systems, ICCPS 2016 - Proceedings. - 9781509017720
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Konferensbidrag (refereegranskat)abstract
- We introduce a scalable observer architecture to estimate the states of a discrete-time linear-time-invariant (LTI) system whose sensors can be manipulated by an attacker. Given the maximum number of attacked sensors, we build on previous results on necessary and sufficient conditions for state estimation, and propose a novel multi-modal Luenberger (MML) observer based on efficient Satisfiability Modulo Theory (SMT) solving. We present two techniques to reduce the complexity of the estimation problem. As a first strategy, instead of a bank of distinct observers, we use a family of filters sharing a single dynamical equation for the states, but different output equations, to generate estimates corresponding to different subsets of sensors. Such an architecture can reduce the memory usage of the observer from an exponential to a linear function of the number of sensors. We then develop an efficient SMT-based decision procedure that is able to reason about the estimates of the MML observer to detect at runtime which sets of sensors are attack-free, and use them to obtain a correct state estimate. We provide proofs of convergence for our algorithm and report simulation results to compare its runtime performance with alternative techniques. Our algorithm scales well for large systems (including up to 5000 sensors) for which many previously proposed algorithms are not implementable due to excessive memory and time requirements. Finally, we illustrate the effectiveness of our algorithm on the design of resilient power distribution systems.
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| 154. |
- Silventoinen, Karri, et al.
(författare)
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Genetic and environmental variation in educational attainment : an individual-based analysis of 28 twin cohorts
- 2020
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the heritability of educational attainment and how it differed between birth cohorts and cultural–geographic regions. A classical twin design was applied to pooled data from 28 cohorts representing 16 countries and including 193,518 twins with information on educational attainment at 25 years of age or older. Genetic factors explained the major part of individual differences in educational attainment (heritability: a2 = 0.43; 0.41–0.44), but also environmental variation shared by co-twins was substantial (c2 = 0.31; 0.30–0.33). The proportions of educational variation explained by genetic and shared environmental factors did not differ between Europe, North America and Australia, and East Asia. When restricted to twins 30 years or older to confirm finalized education, the heritability was higher in the older cohorts born in 1900–1949 (a2 = 0.44; 0.41–0.46) than in the later cohorts born in 1950–1989 (a2 = 0.38; 0.36–0.40), with a corresponding lower influence of common environmental factors (c2 = 0.31; 0.29–0.33 and c2 = 0.34; 0.32–0.36, respectively). In conclusion, both genetic and environmental factors shared by co-twins have an important influence on individual differences in educational attainment. The effect of genetic factors on educational attainment has decreased from the cohorts born before to those born after the 1950s.
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| 155. |
- Stocchero, Michele, et al.
(författare)
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Biomechanical, Biologic, and Clinical Outcomes of Undersized Implant Surgical Preparation : A Systematic Review
- 2016
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Ingår i: International Journal of Oral & Maxillofacial Implants. - : Quintessence. - 0882-2786 .- 1942-4434. ; 31:6, s. 1247-1263
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE: To compile the current evidence on biomechanical, biologic, and clinical outcomes of undersized surgical preparation protocols in dental implant surgery. MATERIALS AND METHODS: An electronic search using three different databases (PubMed, Web of Science, and Cochrane Library) and a manual hand search were performed including in vitro, animal, and clinical studies published prior to October 2015. Studies in which an undersized drilling protocol was compared with a nonundersized drilling protocol were included. RESULTS: From an initial selection of 1,655 titles, 29 studies met the inclusion criteria, including 14 biomechanical, 7 biologic, 6 biologic and biomechanical, and 2 clinical. Due to methodologic variation, meta-analysis was not performed. Several studies showed that implants inserted with an undersized drilling approach reached a significantly higher insertion torque value than conventional drilling in low-density substrates, while this effect is less evident if a thick cortical layer is present. Similar results in terms of boneto-implant contact (BIC) were achieved in the longer term between implants inserted with undersized and nonundersized protocols. Results in the short term were inconclusive. Clinical studies did not show negative outcomes for undersized drilling, although clinical evidence was sparse. No data are available on marginal bone loss. CONCLUSION: From the biomechanical standpoint, an undersized drilling protocol is effective in increasing insertion torque in low-density bone. Biologic response in long-term healing after undersized implant placement is comparable to that in the nonundersized surgical drilling protocol. Clinical studies indicate that performing an undersized drilling protocol on low-density bone is a safe procedure; however, more extensive studies are needed to confirm these data.
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| 156. |
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| 157. |
- Thorell, Kaisa, 1983, et al.
(författare)
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The Helicobacter pylori Genome Project: insights into H. pylori population structure from analysis of a worldwide collection of complete genomes
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics.
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| 158. |
- Torres, João Paulo N., et al.
(författare)
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Effect of reflector geometry in the annual received radiation of low concentration photovoltaic systems
- 2018
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Ingår i: Energies. - : MDPI AG. - 1996-1073. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Solar concentrator photovoltaic collectors are able to deliver energy at higher temperatures for the same irradiances, since they are related to smaller areas for which heat losses occur. However, to ensure the system reliability, adequate collector geometry and appropriate choice of the materials used in these systems will be crucial. The present work focuses on the re-design of the Concentrating Photovoltaic system (C-PV) collector reflector presently manufactured by the company Solarus, together with an analysis based on the annual assessment of the solar irradiance in the collector. An open-source ray tracing code (Soltrace) is used to accomplish the modelling of optical systems in concentrating solar power applications. Symmetric parabolic reflector configurations are seen to improve the PV system performance when compared to the conventional structures currently used by Solarus. The parabolic geometries, using either symmetrically or asymmetrically placed receivers inside the collector, accomplished both the performance and cost-effectiveness goals: for almost the same area or costs, the new proposals for the PV system may be in some cases 70% more effective as far as energy output is concerned.
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| 159. |
- Tröger, Armin, et al.
(författare)
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Tetranorsesquiterpenoids as attractants of yucca moths to yucca flowers
- 2021
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Ingår i: Journal of Chemical Ecology. - : Springer Science and Business Media LLC. - 0098-0331 .- 1573-1561. ; 47:12, s. 1025-1041
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Tidskriftsartikel (refereegranskat)abstract
- The obligate pollination mutualism between Yucca and yucca moths is a classical example of coevolution. Oviposition and active pollination by female yucca moths occur at night when Yucca flowers are open and strongly scented. Thus, floral volatiles have been suggested as key sensory signals attracting yucca moths to their host plants, but no bioactive compounds have yet been identified. In this study, we showed that both sexes of the pollinator moth Tegeticula yuccasella are attracted to the floral scent of the host Yucca filamentosa. Chemical analysis of the floral headspace from six Yucca species in sections Chaenocarpa and Sarcocarpa revealed a set of novel tetranorsesquiterpenoids putatively derived from (E)-4,8-dimethyl-1,3,7-nonatriene. Their structure elucidation was accomplished by NMR analysis of the crude floral scent sample of Yucca treculeana along with GC/MS analysis and confirmed by total synthesis. Since all these volatiles are included in the floral scent of Y. filamentosa, which has been an important model species for understanding the pollination mutualism, we name these compounds filamentolide, filamentol, filamental, and filamentone. Several of these compounds elicited antennal responses in pollinating (Tegeticula) and non-pollinating (Prodoxus) moth species upon stimulation in electrophysiological recordings. In addition, synthetic (Z)-filamentolide attracted significant numbers of both sexes of two associated Prodoxus species in a field trapping experiment. Highly specialized insect-plant interactions, such as obligate pollination mutualisms, are predicted to be maintained through “private channels” dictated by specific compounds. The identification of novel bioactive tetranorsesquiterpenoids is a first step in testing such a hypothesis in the Yucca-yucca moth interaction.
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| 160. |
- Wang, Sophia S., et al.
(författare)
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HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
- 2018
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:14, s. 4086-4096
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Tidskriftsartikel (refereegranskat)abstract
- A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma.
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