| 1. |
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| 2. |
- Kristanl, Matej, et al.
(författare)
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The Seventh Visual Object Tracking VOT2019 Challenge Results
- 2019
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Ingår i: 2019 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE COMPUTER SOC. - 9781728150239 ; , s. 2206-2241
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2019 is the seventh annual tracker benchmarking activity organized by the VOT initiative. Results of 81 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in the recent years. The evaluation included the standard VOT and other popular methodologies for short-term tracking analysis as well as the standard VOT methodology for long-term tracking analysis. The VOT2019 challenge was composed of five challenges focusing on different tracking domains: (i) VOT-ST2019 challenge focused on short-term tracking in RGB, (ii) VOT-RT2019 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2019 focused on long-term tracking namely coping with target disappearance and reappearance. Two new challenges have been introduced: (iv) VOT-RGBT2019 challenge focused on short-term tracking in RGB and thermal imagery and (v) VOT-RGBD2019 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2019, VOT-RT2019 and VOT-LT2019 datasets were refreshed while new datasets were introduced for VOT-RGBT2019 and VOT-RGBD2019. The VOT toolkit has been updated to support both standard short-term, long-term tracking and tracking with multi-channel imagery. Performance of the tested trackers typically by far exceeds standard baselines. The source code for most of the trackers is publicly available from the VOT page. The dataset, the evaluation kit and the results are publicly available at the challenge website(1).
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| 3. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 4. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 5. |
- Kato, Norihiro, et al.
(författare)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 6. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 7. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 8. |
- Schumann, Gunter, et al.
(författare)
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KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377
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Tidskriftsartikel (refereegranskat)abstract
- Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
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| 9. |
- Surendran, Praveen, et al.
(författare)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 10. |
- Takeuchi, Fumihiko, et al.
(författare)
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Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- 2018
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP.
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| 11. |
- Wen, Wanqing, et al.
(författare)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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| 12. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Adare, A., et al.
(författare)
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Centrality dependence of low-momentum direct-photon production in Au plus Au collisions at root s(NN)=200 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:6
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX experiment at RHIC has measured the centrality dependence of the direct photon yield from Au + Au collisions at root s(NN) = 200 GeV down to pT = 0.4 GeV/c. Photons are detected via photon conversions to e(+)e(-) pairs and an improved technique is applied that minimizes the systematic uncertainties that usually limit direct photon measurements, in particular at low pT. We find an excess of direct photons above the N-coll-scaled yield measured in p + p collisions. This excess yield is well described by an exponential distribution with an inverse slope of about 240 MeV/c in the pT range 0.6-2.0 GeV/c. While the shape of the pT distribution is independent of centrality within the experimental uncertainties, the yield increases rapidly with increasing centrality, scaling approximately with N-part(alpha), where alpha = 1.38 +/- 0.03(stat) +/- 0.07(syst).
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| 14. |
- Adare, A., et al.
(författare)
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Evolution of pi(0) Suppression in Au plus Au Collisions from root s(NN)=39 to 200 GeV
- 2012
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Ingår i: Physical Review Letters. - 1079-7114. ; 109:15
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Tidskriftsartikel (refereegranskat)abstract
- Neutral-pion pi(0) spectra were measured at midrapidity (vertical bar y vertical bar < 0.35) in Au + Au collisions at root s(NN) = 39 and 62.4 GeV and compared with earlier measurements at 200 GeV in a transverse-momentum range of 1 < p(T) < 10 GeV/c. The high-p(T) tail is well described by a power law in all cases, and the powers decrease significantly with decreasing center-of-mass energy. The change of powers is very similar to that observed in the corresponding spectra for p + p collisions. The nuclear modification factors (RAA) show significant suppression, with a distinct energy, centrality, and p(T) dependence. Above p(T) = 7 GeV/c, R-AA is similar for root sNN = 62.4 and 200 GeV at all centralities. Perturbative-quantum-chromodynamics calculations that describe R-AA well at 200 GeV fail to describe the 39 GeV data, raising the possibility that, for the same p(T) region, the relative importance of initial-state effects and soft processes increases at lower energies. The p(T) range where pi(0) spectra in central Au + Au collisions have the same power as in p + p collisions is approximate to 5 and 7 GeV/c for root sNN = 200 and 62.4 GeV, respectively. For the root sNN = 39 GeV data, it is not clear whether such a region is reached, and the x(T) dependence of the x(T)-scaling power-law exponent is very different from that observed in the root sNN = 62 and 200 GeV data, providing further evidence that initial-state effects and soft processes mask the in-medium suppression of hardscattered partons to higher p(T) as the collision energy decreases.
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| 15. |
- Adare, A., et al.
(författare)
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Heavy-quark production and elliptic flow in Au plus Au collisions at root(NN)-N-S=62.4 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:4
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of electrons and positrons from the semileptonic decays of heavy-flavor hadrons at midrapidity (vertical bar gamma vertical bar < 0.35) in Au + Au collisions at root(NN)-N-S = 62.4 GeV. The data were collected in 2010 by the PHENIX experiment that included the new hadron-blind detector. The invariant yield of electrons from heavy-flavor decays is measured as a function of transverse momentum in the range 1 < p(T)(e) < 5 GeV/c. The invariant yield per binary collision is slightly enhanced above the p + p reference in Au + Au 0%-20%, 20%-40%, and 40%-60% centralities at a comparable level. At this low beam energy this may be a result of the interplay between initial-state Cronin effects, final-state flow, and energy loss in medium. The v(2) of electrons from heavy-flavor decays is nonzero when averaged between 1.3 < p(T)(e) < 2.5 GeV/c for 0%-40% centrality collisions at root(NN)-N-S = 62.4 GeV. For 20%-40% centrality collisions, the v(2) at root(NN)-N-S = 62.4 GeV is smaller than that for heavy-flavor decays at root(NN)-N-S = 200 GeV. The v2 of the electrons from heavy-flavor decay at the lower beam energy is also smaller than v(2) for pions. Both results indicate that the heavy quarks interact with the medium formed in these collisions, but they may not be at the same level of thermalization with the medium as observed at root(NN)-N-S = 200 GeV.
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| 16. |
- Adare, A., et al.
(författare)
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J/psi suppression at forward rapidity in Au plus Au collisions at root s(NN)=39 and 62.4 GeV
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 86:6
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Tidskriftsartikel (refereegranskat)abstract
- We present measurements of the J/psi invariant yields in root s(NN) = 39 and 62.4 GeV Au + Au collisions at forward rapidity (1.2 < vertical bar y vertical bar < 2.2). Invariant yields are presented as a function of both collision centrality and transverse momentum. Nuclear modifications are obtained for central relative to peripheral Au + Au collisions (R-CP) and for various centrality selections in Au + Au relative to scaled p + p cross sections obtained from other measurements (R-AA). The observed suppression patterns at 39 and 62.4 GeV are quite similar to those previously measured at 200 GeV. This similar suppression presents a challenge to theoretical models that contain various competing mechanisms with different energy dependencies, some of which cause suppression and others enhancement. DOI: 10.1103/PhysRevC.86.064901
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| 17. |
- Adare, A., et al.
(författare)
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Measurement of gamma(1S+2S+3S) production in p plus p and Au plus Au collisions at root sNN=200 GeV
- 2015
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:2
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Tidskriftsartikel (refereegranskat)abstract
- Measurements of bottomonium production in heavy-ion and p + p collisions at the Relativistic Heavy Ion Collider (RHIC) are presented. The inclusive yield of the three states, (1S + 2S + 3S), was measured in the PHENIX experiment via electron-positron decay pairs at midrapidity for Au + Au and p + p collisions at root sNN = 200 GeV. The (1S + 2S + 3S) -> e(+)e(-) differential cross section at midrapidity was found to be B(ee)d sigma/dy = 108 +/- 38 (stat) +/- 15 (syst) +/- 11 (luminosity) pb in p + p collisions. The nuclear modification factor in the 30% most central Au + Au collisions indicates a suppression of the total. state yield relative to the extrapolation from p + p collision data. The suppression is consistent with measurements made by STAR at RHIC and at higher energies by the CMS experiment at the Large Hadron Collider.
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| 18. |
- Adare, A., et al.
(författare)
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Medium Modification of Jet Fragmentation in Au plus Au Collisions at root S-NN=200 GeV Measured in Direct Photon-Hadron Correlations
- 2013
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Ingår i: Physical Review Letters. - 1079-7114. ; 111:3
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Tidskriftsartikel (refereegranskat)abstract
- The jet fragmentation function is measured with direct photon-hadron correlations in p + p and Au + Au collisions at root S-NN = 200 GeV. The P-T of the photon is an excellent approximation to the initial P-T of the jet and the ratio Z(T) = P-T(h)/P-T(gamma) is used as a proxy for the jet fragmentation function. A statistical subtraction is used to extract the direct photon-hadron yields in Au + Au collisions while a photon isolation cut is applied in p + p. I-AA, the ratio of hadron yield opposite the photon in Au + Au to that in p + p, indicates modification of the jet fragmentation function. Suppression, most likely due to energy loss in the medium, is seen at high Z(T). The associated hadron yield at low Z(T) is enhanced at large angles. Such a trend is expected from redistribution of the lost energy into increased production of low-momentum particles.
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| 19. |
- Adare, A., et al.
(författare)
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Nuclear matter effects on J/psi production in asymmetric Cu plus Au collisions at root S-NN=200 GeV
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:6
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Tidskriftsartikel (refereegranskat)abstract
- We report on J/psi production from asymmetric Cu + Au heavy-ion collisions at root S-NN = 200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of J/psi yields in Cu + Au collisions in the Au-going direction is found to be comparable to that inAu + Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, J/psi production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-x gluon suppression in the larger Au nucleus.
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| 20. |
- Chen, Kang, et al.
(författare)
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Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils
- 2009
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 10:8, s. 121-889
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-dependent and T cell-independent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process required activation-induced cytidine deaminase (AID) and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizing receptor that induced antimicrobial, opsonizing, inflammatory and B cell-stimulating factors, including cathelicidin, interleukin 1 (IL-1), IL-4 and B cell-activating factor (BAFF), after IgD crosslinking. By showing dysregulation of IgD class-switched B cells and 'IgD-armed' basophils in autoinflammatory syndromes with periodic fever, our data indicate that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.
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| 21. |
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| 22. |
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| 23. |
- Chen, Yong, et al.
(författare)
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A Vps21 endocytic module regulates autophagy
- 2014
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Ingår i: Molecular Biology of the Cell. - 1939-4586. ; 25:20, s. 3166-3177
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Tidskriftsartikel (refereegranskat)abstract
- In autophagy, the double-membrane autophagosome delivers cellular components for their degradation in the lysosome. The conserved Ypt/Rab GTPases regulate all cellular trafficking pathways, including autophagy. These GTPases function in modules that include guanine-nucleotide exchange factor (GEF) activators and downstream effectors. Rab7 and its yeast homologue, Ypt7, in the context of such a module, regulate the fusion of both late endosomes and autophagosomes with the lysosome. In yeast, the Rab5-related Vps21 is known for its role in early- to late-endosome transport. Here we show an additional role for Vps21 in autophagy. First, vps21Δ mutant cells are defective in selective and nonselective autophagy. Second, fluorescence and electron microscopy analyses show that vps21Δ mutant cells accumulate clusters of autophagosomal structures outside the vacuole. Third, cells with mutations in other members of the endocytic Vps21 module, including the GEF Vps9 and factors that function downstream of Vps21, Vac1, CORVET, Pep12, and Vps45, are also defective in autophagy and accumulate clusters of autophagosomes. Finally, Vps21 localizes to PAS. We propose that the endocytic Vps21 module also regulates autophagy. These findings support the idea that the two pathways leading to the lysosome—endocytosis and autophagy—converge through the Vps21 and Ypt7 GTPase modules.
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| 24. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 25. |
- He, Bing, et al.
(författare)
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Lmx1b and FoxC Combinatorially Regulate Podocin Expression in Podocytes
- 2014
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 25:12, s. 2764-2777
-
Tidskriftsartikel (refereegranskat)abstract
- Podocin is a key protein of the kidney podocyte slit diaphragm protein complex, an important part of the glomerular filtration barrier. Mutations in the human podocin gene NPHS2 cause familial or sporadic forms of renal disease owing to the disruption of filtration barrier integrity. The exclusive expression of NPHS2 in podocytes reflects its unique function and raises interesting questions about its transcriptional regulation. Here, we further define a 2.5-kb zebrafish nphs2 promoter fragment previously described and identify a 49-bp podocyte-specific transcriptional enhancer using Tol2-mediated G(0) transgenesis in zebrafish. Within this enhancer, we identified a cis-acting element composed of two adjacent DNA-binding sites (FLAT-E and forkhead) bound by transcription factors Lnnx1b and FoxC. In zebrafish, double knockdown of Lmx1b and FoxC orthologs using morpholino doses that caused no or minimal phenotypic changes upon individual knockdown completely disrupted podocyte development in 40% of injected embryos. Co-overexpression of the two genes potently induced endogenous nphs2 expression in zebrafish podocytes. We found that the NPHS2 promoter also contains a cis-acting Lmx1b-FoxC motif that binds LMX1B and FoxC2. Furthermore, a genome-wide search identified several genes that carry the Lmx1b-FoxC motif in their promoter regions. Among these candidates, motif-driven podocyte enhancer activity of CCNC and MEIS2 was functionally analyzed in vivo. Our results show that podocyte expression of some genes is combinatorially regulated by two transcription factors interacting synergistically with a common enhancer. This finding provides insights into transcriptional mechanisms required for normal and pathologic podocyte functions.
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| 26. |
- He, Bing, et al.
(författare)
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Single-cell RNA sequencing reveals the mesangial identity and species diversity of glomerular cell transcriptomes
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular characterization of the individual cell types in human kidney as well as model organisms are critical in defining organ function and understanding translational aspects of biomedical research. Previous studies have uncovered gene expression profiles of several kidney glomerular cell types, however, important cells, including mesangial (MCs) and glomerular parietal epithelial cells (PECs), are missing or incompletely described, and a systematic comparison between mouse and human kidney is lacking. To this end, we use Smart-seq2 to profile 4332 individual glomerulus-associated cells isolated from human living donor renal biopsies and mouse kidney. The analysis reveals genetic programs for all four glomerular cell types (podocytes, glomerular endothelial cells, MCs and PECs) as well as rare glomerulus-associated macula densa cells. Importantly, we detect heterogeneity in glomerulus-associated Pdgfrb-expressing cells, including bona fide intraglomerular MCs with the functionally active phagocytic molecular machinery, as well as a unique mural cell type located in the central stalk region of the glomerulus tuft. Furthermore, we observe remarkable species differences in the individual gene expression profiles of defined glomerular cell types that highlight translational challenges in the field and provide a guide to design translational studies. The molecular identity of renal glomerular cells is poorly characterized and rodent glomerulopathy models translate poorly to humans. Here, the authors show molecular signatures of glomerulus-associated cells using single cell RNA sequencing and highlight differences between mouse and human cells.
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| 27. |
- He, Bing
(författare)
-
Susceptibility gene mapping in multiple sclerosis
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Multiple sclerosis (MS) is a chronic inflammatory disease characterized by relapsing or progressive demyelination of the central nervous system (CNS). Increasing evidence supports that genetic factors confer susceptibility to MS resulting in an unknown mode of inheritance as a complex trait. Although the HLA region has been identified as important in MS, non-HLA loci have not been clearly identified. Autoimmunity to self-myelin components has been proposed as being of key importance in the pathogenesis of MS. Therefore, major myelin proteins and critical regulatory factors involved in autoimmune responses could be considered to be candidates for genetic analysis in MS. The gene encoding myelin basic protein (MBP), a potential autoantigen in MS, has been reported linked and associated with MS in the Finnish population, but this observation lacks confirmation in other populations. A limitation of previous studies has been the low resolution of the typing procedure. We performed linkage and case-control analyses with the same MBP gene polymorphic marker genotyped by use of a fluorescence-based DNA sequencer which allowed the identification of discrete alleles of a 1.3 kb tetranucleotide repeat. Our results did not provide any evidence for linkage or association with Swedish MS families and patients. Tumor necrosis factor-a (TNF-a) is a potent proinflammatory cytokine which is thought to have a proinflammatory role in MS. We investigated a bi-allelic polymorphism in the TNF-a promoter at position -308 bp (TNFa-308), which is reported to influence transcriptional activity, in a group of patient with MS and optic neuritis using an allele-specific PCR technique, and correlated the genotypes with nurnbers of TNF-a mRNA expressing cells. No significant difference was found in the distribution of TNFa-308 alleles between patients and controls was found. TNFa-308 alleles did not correlate with numbers of TNF-a mRNA expressing cells in patients. Autoantibodies may participate in the pathogenesis of MS. We studied a highly polymorphic VNTR marker located in the centre of the Ig heavy chain locus in a number of MS families and sporadic patients. No evidence was found for linkage or association of this marker with Swedish families and MS patients. We further investigated a number of candidated genes in MS, genes encoding cytokines (IFN-y, IL-2, IL-4, IL-4 receptor, IL-10, TGF-,ß1 and -,ß2) and myelin proteins (CNP:ase, MAG, OMGP, PLP) in MS by two-point linkage, affected pedigree member (APM) and association analyses. No evidence for linkage was observed except for a slightly positive lod score of 0.88 (0 = 0.01) for IFN-y. APM analysis indicated a possible linkage with TGF-ß2 (p = 0.008) and IL-4R (p = 0.043). None of the cytokine markers were associated with MS. A genetically isolated Swedish population with a high prevalence of MS was studied using a haplotype sharing method. We searched for haplotypes shared by affected individuals in a large kindred by genome search of 4 nuclear families and located regions demonstrating identity-by descent by linkage disequilibrium analysis. Our data suggest the location of a gene with an importance for MS in this population at chromosome 17p.
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| 28. |
- He, Yixing, et al.
(författare)
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Chain Length Modulated Dimerization and Cyclization of Terminal Thienyl-Blocked Oligopyrranes
- 2022
-
Ingår i: Organic Letters. - : AMER CHEMICAL SOC. - 1523-7060 .- 1523-7052. ; 24:29, s. 5428-5432
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Tidskriftsartikel (refereegranskat)abstract
- Oxidation of thienyl-blocked bilane and pentapyrrane afforded chain length dependent products of the symmetric dimer D1 and the thienyloligopyrrin-appended pentaphyrin analogue P2, respectively, with the latter formed by simultaneous dimerization and cyclization. Coordination of D1 and P2 with Cu(II) afforded di-and monometallic complexes D1-Cu2 and P2 -Cu, respectively. These compounds exhibit distinct NIR absorption, with the absorption tail of D1-Cu2 extended to ca. 1900 nm despite its smaller conjugation framework than that of P2 -Cu.
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| 29. |
- Huang, Yimin, et al.
(författare)
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Facile synthesis of sodium lignosulfonate/polyethyleneimine/sodium alginate beads with ultra-high adsorption capacity for Cr(VI) removal from water
- 2022
-
Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 436
-
Tidskriftsartikel (refereegranskat)abstract
- Chromium (VI) is a widely occurring toxic heavy metal ion in industrial wastewater that seriously impacts the environment. In this study, we used environmentally friendly sodium lignosulfonate (SL), polyethyleneimine (PEI), and sodium alginate (SA) to synthesize SL/PEI/SA beads by employing a simple crosslinking method with to develop a novel absorbent with excellent adsorption capacity and practical application in wastewater treatment. We studied the adsorption performance of SL/PEI/SA through batch adsorption and continuous dynamic adsorption experiments. SL/PEI/SA has ultra-high adsorption capacity (2500 mg·g-1) at 25 ℃, which is much higher than that of existing adsorbents. Humic acids and coexisting anions commonly found in wastewater have minimal effect on the adsorption performance of SL/PEI/SA. In the column system, 1 g SL/PEI/SA can treat 8.1 L secondary electroplating wastewater at a flow rate of 0.5 mLmin-1, thereby enabling the concentration of Cr(VI) in secondary electroplating wastewater to meet the discharge standard (< 0.2 mg·L-1). It is worth noting that the concentration of competitive ions in secondary electroplating wastewater is more than 500 times higher than that of Cr(VI). These results demonstrate that the novel SL/PEI/SA beads can be effectively applied in the removal of Cr(VI) in wastewater.
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| 30. |
- Jiang, Bing-Xin, et al.
(författare)
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Fabrication and bonding of In bumps on Micro-LED with 8 μ m pixel pitch
- 2024
-
Ingår i: ENGINEERING RESEARCH EXPRESS. - 2631-8695. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- Indium (In) is currently used to fabricate metal bumps on micro-light-emitting diode (Micro-LED) chips due to its excellent physical properties. However, as Micro-LED pixel size and pitch decrease, achieving high-quality In bumps on densely packed Micro-LED chips often presents more challenges. This paper describes the process of fabricating In bumps on micro-LEDs using thermal evaporation, highlighting an issue where In tends to grow laterally within the photoresist pattern, ultimately blocking the pattern and resulting in undersized and poorly dense In bumps on the Micro-LED chip. To address this issue, we conducted numerous experiments to study the height variation of In bumps within a range of photoresist aperture sizes (3 mu m -7 mu m) under two different resist thickness conditions (3.8 mu m and 4.8 mu m). The results showed that the resist thickness had a certain effect on the height of In bumps on the Micro-LED chip electrodes. Moreover, we found that, with the photoresist pattern size increasing under constant resist thickness conditions, the height and quality of the bumps significantly improved. Based on this finding, we rationalized the adjustment of the photoresist pattern size within a limited emission platform range to compensate for the height difference of In bumps caused by different resist thicknesses between the cathode and anode regions. Consequently, well-shaped and dense In bumps with a maximum height of up to 4.4 mu m were fabricated on 8 mu m pitch Micro-LED chips. Afterwards, we bonded the Micro-LED chip with indium bumps to the CMOS chip, and we found that we could successfully control the CMOS chip to drive the Micro-LED chip to display specific characters through the Flexible Printed Circuit (FPC). This work is of significant importance for the fabrication of In bumps on Micro-LED chips with pitches below 10 mu m and subsequent bonding processes.
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| 31. |
- Jiao, Xingxing, et al.
(författare)
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Crumpled Nitrogen-Doped Graphene-Wrapped Phosphorus Composite as a Promising Anode for Lithium-Ion Batteries
- 2019
-
Ingår i: ACS Applied Materials & Interfaces. - : American Chemical Society (ACS). - 1944-8252 .- 1944-8244. ; 11:34, s. 30858-30864
-
Tidskriftsartikel (refereegranskat)abstract
- Red phosphorus (P) has recently gained wide attention because of the high theoretical capacity of 2596 mA h/g, which has been regarded as promising anode material for lithium-ion batteries (LIBs). However, the actual application of red P in LIBs is hampered by the huge expansion of volume and low electronic conductivity. Herein, we design a kind of red phosphorus/crumpled nitrogen-doped graphene (P/CNG) nanocomposites with high capacity density and great rate performance as anode material for LIBs. This anode material was rationally fabricated through the scalable ball-milling method. The nanocomposite structure of P/CNG improves the electron conductivity and alleviates volume change of raw red P because of the three-dimension (3D) framework, massive defects and active sites of CNG sheets. As expected, the P/CNG composite shows excellent electrochemical performances, including high capacity (2522.6 mA h/g at 130 mA/g), remarkable rate capability (1340.5 mA h/g at 3900 mA/g), and great cyclability (1470.1 mA h/g at 1300 mA/g for 300 cycles). This work may provide a broad prospect for a great rate performance of P-based anode material for LIBs.
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| 32. |
- Meng, Mei, et al.
(författare)
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Accumulation of total mercury and methylmercury in rice plants collected from different mining areas in China
- 2014
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Ingår i: Environmental Pollution. - : Pergamon Press. - 0269-7491 .- 1873-6424. ; 184, s. 179-186
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Tidskriftsartikel (refereegranskat)abstract
- A total of 155 rice plants were collected from ten mining areas in three provinces of China (Hunan, Guizhou and Guangdong), where most of mercury (Hg) mining takes place in China. During the harvest season, whole rice plants were sampled and divided into root, stalk & leaf, husk and seed (brown rice), together with soil from root zone. Although the degree of Hg contamination varied significantly among different mining areas, rice seed showed the highest ability for methylmercury (MeHg) accumulation. Both concentrations of total mercury (THg) and MeHg in rice plants were significantly correlated with Hg levels in soil, indicating soil is still an important source for both inorganic mercury (IHg) and MeHg in rice plants. The obvious discrepancy between the distribution patterns of THg and MeHg reflected different pathways of IHg and MeHg accumulation. Water soluble Hg may play more important role in MeHg accumulation in rice plants.
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| 33. |
- Meng, Zhiwei, 1996, et al.
(författare)
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Interaction-Aware Trajectory Prediction for Autonomous Vehicle Based on LSTM-MLP Model
- 2023
-
Ingår i: Smart Innovation, Systems and Technologies. - 2190-3026 .- 2190-3018. ; 356, s. 91-99
-
Konferensbidrag (refereegranskat)abstract
- Trajectory prediction is one of the core functions of the autonomous vehicle, it greatly affects the rationality and safety of the decision-making module and the planning module. This is challenging because the motion of the target vehicle is affected by the interactive behavior of its surrounding vehicles. In this paper, we propose the interaction-aware trajectory prediction model for autonomous vehicles based on LSTM-MLP model. The encoder module encoded the history trajectories to extract the dynamic feature of each vehicle in the scenarios by the LSTM model, and then the interaction module captures the interactive feature using the MLP-Max Pooling model. In the end, the decoder module decodes the fusion feature which consists of the dynamic feature of the target vehicle and the interactive feature to output the future trajectory based on the LSTM model. The experiments are carried out on the publicly available NGSIM dataset, and the results show that the proposed model outperforms prior works in terms of RMSE value.
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| 34. |
- Mueller, Christian P., et al.
(författare)
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The Cortical Neuroimmune Regulator TANK Affects Emotional Processing and Enhances Alcohol Drinking : A Translational Study
- 2019
-
Ingår i: Cerebral Cortex. - : OXFORD UNIV PRESS INC. - 1047-3211 .- 1460-2199. ; 29:4, s. 1736-1751
-
Tidskriftsartikel (refereegranskat)abstract
- Alcohol abuse is a major public health problem worldwide. Understanding the molecular mechanisms that control regular drinking may help to reduce hazards of alcohol consumption. While immunological mechanisms have been related to alcohol drinking, most studies reported changes in immune function that are secondary to alcohol use. In this report, we analyse how the gene "TRAF family member-associated NF-kappa B activator" (TANK) affects alcohol drinking behavior. Based on our recent discovery in a large GWAS dataset that suggested an association of TANK, SNP rs197273, with alcohol drinking, we report that SNP rs197273 in TANK is associated both with gene expression (P = 1.16 x 10(-19)) and regional methylation (P = 5.90 x 10(-25)). A tank knock out mouse model suggests a role of TANK in alcohol drinking, anxiety-related behavior, as well as alcohol exposure induced activation of insular cortex NF-kappa B. Functional and structural neuroimaging studies among up to 1896 adolescents reveal that TANK is involved in the control of brain activity in areas of aversive interoceptive processing, including the insular cortex, but not in areas related to reinforcement, reward processing or impulsiveness. Our findings suggest that the cortical neuroimmune regulator TANK is associated with enhanced aversive emotional processing that better protects from the establishment of alcohol drinking behavior.
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| 35. |
- Nishibori, Yukino, et al.
(författare)
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Glcci1 Deficiency Leads to Proteinuria
- 2011
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:11, s. 2037-2046
-
Tidskriftsartikel (refereegranskat)abstract
- Unbiased transcriptome profiling and functional genomics approaches identified glucocorticoid-induced transcript 1 (GLCCI1) as being a transcript highly specific for the glomerulus, but its role in glomerular development and disease is unknown. Here, we report that mouse glomeruli express far greater amounts of Glcci1 protein compared with the rest of the kidney. RT-PCR and Western blotting demonstrated that mouse glomerular Glcci1 is approximately 60 kD and localizes to the cytoplasm of podocytes in mature glomeruli. In the fetal kidney, intense Glcci1 expression occurs at the capillary-loop stage of glomerular development. Using gene knockdown in zebrafish with morpholinos, morphants lacking Glcci1 function had collapsed glomeruli with foot-process effacement. Permeability studies of the glomerular filtration barrier in these zebrafish morphants demonstrated a disruption of the selective glomerular permeability filter. Taken together, these data suggest that Glcci1 promotes the normal development and maintenance of podocyte structure and function.
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| 36. |
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| 37. |
- Rodriguez, Patricia Q., et al.
(författare)
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Knockdown of Tmem234 in zebrafish results in proteinuria
- 2015
-
Ingår i: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY. - : American Physiological Society. - 1931-857X .- 1522-1466. ; 309:11, s. F955-F966
-
Tidskriftsartikel (refereegranskat)abstract
- Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features, podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte-enriched proteins. The proteins are strongly expressed by podocytes, while other parts of the kidney show only weak or no expression. Tmem234, Slfn5, and Lrrc49 are located in foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologs for Tmem234 and Znf185 genes and knocked down their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephric glomerulus filtration barrier, as inactivation of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified four novel highly podocyte - enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in the zebrafish pronephric glomerulus. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in glomerulus biology and diseases.
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| 38. |
- Sandholm, Niina, et al.
(författare)
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Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes
- 2014
-
Ingår i: Diabetologia. - Berlin Heidelberg : Springer-Verlag. - 0012-186X .- 1432-0428. ; 57:6, s. 1143-1153
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes.METHODS: The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10(-4) were followed up in 3,750 additional patients withtype 1 diabetes from seven studies.RESULTS: The narrow-sense heritability, captured with our genotyping platform, was estimated to explain 27.3% of the total AER variability, and 37.6% after adjustment for covariates. In the discovery stage, five single nucleotide polymorphisms in the GLRA3 gene were strongly associated with albuminuria (p < 5 × 10(-8)). In the replication group, a nominally significant association (p = 0.035) was observed between albuminuria and rs1564939 in GLRA3, but this was in the opposite direction. Sequencing of the surrounding genetic region in 48 Finnish and 48 UK individuals supported the possibility that population-specific rare variants contribute to the synthetic associationobserved at the common variants in GLRA3. The strongest replication (p = 0.026) was obtained for rs2410601 between the PSD3 and SH2D4A genes. Pathway analysis highlighted natural killer cell mediated immunity processes.CONCLUSIONS/INTERPRETATION: This study suggests novel pathways and molecular mechanisms for the pathogenesis of albuminuria in type 1 diabetes.
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| 39. |
- Sandholm, Niina, et al.
(författare)
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New susceptibility loci associated with kidney disease in type 1 diabetes
- 2012
-
Ingår i: PLOS Genetics. - San Francisco, USA : Public Library of Science, PLOS. - 1553-7390 .- 1553-7404. ; 8:9, s. e1002921-
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising similar to 2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 x 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 x 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-beta 1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 x 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
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| 40. |
- Schuettpelz, Eric, et al.
(författare)
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A community-derived classification for extant lycophytes and ferns
- 2016
-
Ingår i: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
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Tidskriftsartikel (refereegranskat)abstract
- Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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| 41. |
- Sliz, E., et al.
(författare)
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Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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| 42. |
- Sun, Bing, et al.
(författare)
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Wavelength-Spacing-Tunable Double-Pumped Multiwavelength Optical Parametric Oscillator Based on a Mach-Zehnder Interferometer
- 2012
-
Ingår i: Journal of Lightwave Technology. - 0733-8724 .- 1558-2213. ; 30:12, s. 1937-1942
-
Tidskriftsartikel (refereegranskat)abstract
- A novel double-pumped ring cavity multiwavelength fiber optical parametric oscillator (MW-FOPO) with tunable wavelength spacing is proposed. In the MW-FOPO, we utilize a highly nonlinear dispersion-shifted fiber as the gain medium and a Mach-Zehnder interferometer as the comb-like filter. Twenty-four-wavelength lasing of the double-pumped MW-FOPO with a ripple less than +/- 4.3 dB and a wavelength spacing of about 0.8 nm in a wavelength range from 1541 to 1558 nm is experimentally demonstrated. The wavelength spacing can be continuously tuned and multiwavelength lasings with wavelength spacings of 0.08, 0.2, 0.4, and 0.8 nm are demonstrated, respectively. We discussed the power stability of the multiwavelength lasing of the double-pumped MW-FOPO. A comparison of the output spectra among the double-pumped MW-FOPO, the single-pumped MW-FOPO, and the multiwavelength erbium-doped fiber laser is also presented.
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| 43. |
- Sun, Hui, et al.
(författare)
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Luminosity Function and Event Rate Density of XMM-Newton-selected Supernova Shock Breakout Candidates
- 2022
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 927:2
-
Tidskriftsartikel (refereegranskat)abstract
- A dozen X-ray supernova shock breakout (SN SBO) candidates were reported recently based on XMM-Newton archival data, which increased the X-ray-selected SN SBO sample by an order of magnitude. Assuming that they are genuine SN SBOs, we study the luminosity function (LF) by improving on the method used in our previous work. The light curves and the spectra of the candidates were used to derive the maximum volume within which these objects could be detected with XMM-Newton by simulation. The results show that the SN SBO LF can be described by either a broken power law (BPL) with indices (at the 68% confidence level) of 0.48 +/- 0.28 and 2.11 +/- 1.27 before and after the break luminosity at log(L-b/erg s(-1)) = 45.32 +/- 0.55 or a single power law (SPL) with an index of 0.80 +/- 0.16. The local event rate densities of SN SBOs above 5 x 10(42) erg s (-1) are consistent for two models, i.e., 4.6(-1.3)(+1.7) x 10(4) Gpc(-3) yr(-1) and 4.9(-1.4)(+1.9 )x 10(4) Gpc(-3) yr(-1) for BPL and SPL models, respectively. The number of fast X-ray transients of SN SBO origin can be significantly increased by wide-field X-ray telescopes such as the Einstein Probe.
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| 44. |
- Wang, Xiang-Gao, et al.
(författare)
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HOW BAD OR GOOD ARE THE EXTERNAL FORWARD SHOCK AFTERGLOW MODELS OF GAMMA-RAY BURSTS?
- 2015
-
Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 219:1
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Tidskriftsartikel (refereegranskat)abstract
- The external forward shock models have been the standard paradigm to interpret the broadband afterglow data of gamma-ray bursts (GRBs). One prediction of the models is that some afterglow temporal breaks at different energy bands should be achromatic; that is, the break times should be the same in different frequencies. Multiwavelength observations in the Swift era have revealed chromatic afterglow behaviors at least in some GRBs, casting doubts on the external forward shock origin of GRB afterglows. In this paper, using a large sample of GRBs with both X-ray and optical afterglow data, we perform a systematic study to address the question: how bad or good are the external forward shock models? Our sample includes 85 GRBs up to 2014 March with well-monitored X-ray and optical light curves. Based on how well the data abide by the external forward shock models, we categorize them into five grades and three samples. The first two grades (Grade I and II) include 45 of 85 GRBs. They show evidence of, or are consistent with having, an achromatic break. The temporal and spectral behaviors in each afterglow segment are consistent with the predictions (the "closure relations") of the forward shock models. These GRBs are included in the Gold sample. The next two grades (Grade III and IV) include 37 of 85 GRBs. They are also consistent with having an achromatic break, even though one or more afterglow segments do not comply with the closure relations. These GRBs are included in the Silver sample. Finally, Grade V (3/85) shows direct evidence of chromatic behaviors, suggesting that the external shock models are inconsistent with the data. These are included in the Bad sample. We further perform statistical analyses of various observational properties (temporal index alpha, spectral index beta, break time t(b)) and model parameters (energy injection index q, electron spectral index p, jet opening angle theta(j), radiative efficiency eta(gamma), and so on) of the GRBs in the Gold sample, and derive constraints on the magnetization parameter epsilon(B) in the forward shock. Overall, we conclude that the simplest external forward shock models can account for the multiwavelength afterglow data of at least half of the GRBs. When more advanced modeling (e.g., long-lasting reverse shock, structured jets, arbitrary circumburst medium density profile) is invoked, up to >90% of the afterglows may be interpreted within the framework of the external shock models.
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| 45. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 46. |
- Wei, Ting, et al.
(författare)
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Developed and developing world responsibilities for historical climate change and CO2 mitigation
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:32, s. 12911-12915
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Tidskriftsartikel (refereegranskat)abstract
- At the United Nations Framework Convention on Climate Change Conference in Cancun, in November 2010, the Heads of State reached an agreement on the aim of limiting the global temperature rise to 2 degrees C relative to preindustrial levels. They recognized that long-term future warming is primarily constrained by cumulative anthropogenic greenhouse gas emissions, that deep cuts in global emissions are required, and that action based on equity must be taken to meet this objective. However, negotiations on emission reduction among countries are increasingly fraught with difficulty, partly because of arguments about the responsibility for the ongoing temperature rise. Simulations with two earth-system models (NCAR/CESM and BNU-ESM) demonstrate that developed countries had contributed about 60-80%, developing countries about 20-40%, to the global temperature rise, upper ocean warming, and sea-ice reduction by 2005. Enacting pledges made at Cancun with continuation to 2100 leads to a reduction in global temperature rise relative to business as usual with a 1/3-2/3 (CESM 33-67%, BNU-ESM 35-65%) contribution from developed and developing countries, respectively. To prevent a temperature rise by 2 degrees C or more in 2100, it is necessary to fill the gap with more ambitious mitigation efforts.
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| 47. |
- Xie, Yuan, et al.
(författare)
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Wnt signaling regulates MFSD2A-dependent drug delivery through endothelial transcytosis in glioma
- 2023
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 25:6, s. 1073-1084
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Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic delivery of anti-tumor therapeutic agents to brain tumors is thwarted by the blood-brain barrier (BBB), an organotypic specialization of brain endothelial cells (ECs). A failure of pharmacological compounds to cross BBB is one culprit for the dismal prognosis of glioblastoma (GBM) patients. Identification of novel vascular targets to overcome the challenges posed by the BBB in tumors for GBM treatment is urgently needed.Methods: Temozolomide (TMZ) delivery was investigated in CT2A and PDGFB-driven RCAS/tv-a orthotopic glioma models. Transcriptome analysis was performed on ECs from murine gliomas. Mfsd2a deficient, Cav1 deficient, and Mfsd2a EC-specific inducible mice were developed to study the underlying molecular mechanisms.Results: We demonstrated that inhibiting Wnt signaling by LGK974 could increase TMZ delivery and sensitize glioma to chemotherapy in both murine glioma models. Transcriptome analysis of ECs from murine gliomas revealed that Wnt signaling inhibition enhanced vascular transcytosis as indicated by the upregulation of PLVAP and downregulation of MFSD2A. Mfsd2a deficiency in mice enhances TMZ delivery in tumors, whereas constitutive expression of Mfsd2a in ECs suppresses the enhanced TMZ delivery induced by Wnt pathway inhibition in murine glioma. In addition, Wnt signaling inhibition enhanced caveolin-1 (Cav1)-positive caveolae-mediated transcytosis in tumor ECs. Moreover, Wnt signaling inhibitor or Mfsd2a deficiency fails to enhance TMZ penetration in tumors from Cav1-deficient mice.Conclusions: These results demonstrated that Wnt signaling regulates MFSD2A-dependent TMZ delivery through a caveolae-mediated EC transcytosis pathway. Our findings identify Wnt signaling as a promising therapeutic target to improve drug delivery for GBM treatment.
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| 48. |
- Xu, Fang, et al.
(författare)
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Synthesis, structure-activity relationship and biological evaluation of novel arylpiperzines as alpha(1A/1D)-AR subselective antagonists for BPH
- 2015
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier. - 0968-0896 .- 1464-3391. ; 23:24, s. 7735-7742
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Tidskriftsartikel (refereegranskat)abstract
- A series of novel arylpiperazine derivatives as alpha(1A/1D)-adrenergic receptors (AR) subtype selective antagonists were designed, synthesized and evaluated for their antagonistic activities towards alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)). Compounds 9, 12, 13, 15, 17, 18, 21, 22, 25 and 26 exerted strong antagonistic effects on alpha(1A) and/or alpha(1D) subtypes over alpha(1B) in vitro. SAR analysis indicated that chloride at the ortho-phenyl position for compound 17 was beneficial for the highest alpha(1A/D)-AR sub-selectivity. Moreover, molecular docking study of compound 17 with the homology-modeled alpha(1)-ARs (alpha(1A), alpha(1B), and alpha(1D)) structures exhibited differences of key amino resides in the docking pocket which may influence the subtype selectivity. ILE 193 of alpha(1A) was validated as the key residues for binding ligand. This work provides useful information for finding more new potential drugs in clinic in treating benign prostatic hyperplasia (BPH).
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| 49. |
- Zhang, Shuangshuang, et al.
(författare)
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Discovery of carbon-based strongest and hardest amorphous material
- 2022
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Ingår i: National Science Review. - : Oxford University Press. - 2095-5138 .- 2053-714X. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carbon is one of the most fascinating elements due to its structurally diverse allotropic forms stemming from its bonding varieties (sp, sp2, and sp3). Exploring new forms of carbon has always been the eternal theme of scientific research. Herein, we report the amorphous (AM) carbon materials with high fraction of sp3 bonding recovered from compression of fullerene C60 under high pressure and high temperature previously unexplored. Analysis of photoluminescence and absorption spectra demonstrates that they are semiconducting with a bandgap range of 1.5–2.2 eV, comparable to that of widely used amorphous silicon. Comprehensive mechanical tests demonstrate that the synthesized AM-III carbon is the hardest and strongest amorphous material known so far, which can scratch diamond crystal and approach its strength. The produced AM carbon materials combine outstanding mechanical and electronic properties, and may potentially be used in photovoltaic applications that require ultrahigh strength and wear resistance.
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| 50. |
- Zhang, Shuangshuang, et al.
(författare)
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Narrow-gap, semiconducting, superhard amorphous carbon with high toughness, derived from C60 fullerene
- 2021
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Ingår i: Cell Reports Physical Science. - : Elsevier. - 2666-3864. ; 2:9
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Tidskriftsartikel (refereegranskat)abstract
- New carbon forms that exhibit extraordinary physicochemical properties can be generated from nanostructured precursors under extreme pressure. Nevertheless, synthesis of such fascinating materials is often not well understood. That is the case of the C60 precursor, with irreproducible results that impede further progress in the materials design. Here, the semiconducting amorphous carbon, having band gaps of 0.1–0.3 eV and the advantages of isotropic superhardness and superior toughness over single-crystal diamond and inorganic glasses, is produced from fullerene at high pressure and moderate temperatures. A systematic investigation of the structure and bonding evolution is carried out with complementary characterization methods, which helps to build a model of the transformation that can be used in further high-pressure/high-temperature (high p,T) synthesis of novel nano-carbon systems for advanced applications. The amorphous carbon materials produced have the potential of accomplishing the demanding optoelectronic applications that diamond and graphene cannot achieve.
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