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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Hua, Wenjing, et al.
(författare)
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Genotypic and Phenotypic Analyses of Two "Isogenic" Strains of the Human Fungal Pathogen Cryptococcus neoformans var. neoformans
- 2019
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Ingår i: Mycopathologia. - : SPRINGER. - 0301-486X .- 1573-0832. ; 184:2, s. 195-212
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Tidskriftsartikel (refereegranskat)abstract
- The Cryptococcus neoformans species complex is a model organism for fungal studies. Many studies have used two strains, JEC20 and JEC21, and their derivatives. These two strains were obtained through 10 rounds of backcrosses and have been assumed near identical except at the mating-type locus. Here we obtained and compared the JEC20 genome sequence with the published JEC21 genome. Our comparison revealed 5322 single nucleotide polymorphisms (SNPs) with the majority (N=3816, 71.7%) located in three genomic regions, including the previously noted mating-type region. The remaining 1506 SNPs (28.3%) were distributed throughout all 14 chromosomes, predominantly at chromosomal ends. To study the potential effects of these three SNP-rich regions on phenotypes, 24 progenies from the JEC20xJEC21 cross representing eight recombinant genotypes were analyzed for their mating ability, melanin production, capsule formation, and growths at 30 degrees C and 40 degrees C. Significant phenotypic variations were found among the progeny. However, the observed phenotypic variations could not be explained by the three SNP-rich regions. Further genome sequencing of our JEC21 and the 24 progenies revealed only six segregating SNPs outside of the three SNP-rich regions between JEC20 and JEC21, a result indicating that the 1500 SNPs identified in the published JEC21 genome might be caused by sequencing errors and/or strain mixing. However, the six SNPs and the three SNP-rich regions could not explain the observed phenotypic variations. Our analyses suggest that spontaneous mutations accumulated under laboratory conditions could have significant effects on phenotypes and on our interpretations of experimental results.
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| 4. |
- Jiang, Ziyu, et al.
(författare)
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HLA class I genes modulate disease risk and age at onset together with DR-DQ in Chinese patients with insulin-requiring type 1 diabetes
- 2021
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64:9, s. 2026-2036
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: The study aimed to investigate the effects of HLA class I genes on susceptibility to type 1 diabetes with different onset ages, in addition to the well-established effects of HLA class II genes. Methods: A total of 361 patients with type 1 diabetes (192 patients with onset <18 years and 169 patients with onset ≥18 years) and 500 healthy control participants from China were enrolled and genotyped for the HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 genes using next-generation sequencing. Results: The susceptible DR3 (β = −0.09, p = 0.0009) and DR4-DQ8 (β = −0.13, p = 0.0059) haplotypes were negatively associated with onset age, while the protective DR11 (β = 0.21, p = 0.0314) and DR12 (β = 0.27, p < 0.0001) haplotypes were positively associated with onset age. After adjustment for linkage disequilibrium with DR-DQ haplotypes, A*11:01:01 was positively associated with onset age (β = 0.06, p = 0.0370), while the susceptible C*15:02:01 was negatively associated with onset age (β = −0.21, p = 0.0050). The unit for β was double square-root (fourth root) transformed years of change in onset age associated with per copy of the HLA haplotype/allele. In addition, B*46:01:01 was protective (OR 0.41, 0.46; pc [corrected for multiple comparisons] = 0.0044, 0.0040), whereas A*24:02:01 (OR 2.71, 2.25; pc = 0.0003, 0.0002) and B*54:01:01 (OR 3.96, 3.79; pc = 0.0018, 0.0004) were predisposing in both the <18 group and the ≥18 group compared with healthy control participants. In the context of DR4-DQ4, A*11:01:01 (61.29% vs 28.26%, pc = 0.0144) was increased while the predisposing A*24:02:01 (19.35% vs 47.83%, pc = 0.0403) was decreased in patients with onset ≥18 years when compared with patients with onset <18 years. Conclusions/interpretation: In addition to DR-DQ haplotypes, novel HLA class I alleles were detected to play a role in susceptibility to type 1 diabetes with different onset ages, which could improve the understanding of disease heterogeneity and has implications for the design of future studies. Graphical abstract: [Figure not available: see fulltext.].
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- Kristan, Matej, et al.
(författare)
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The Visual Object Tracking VOT2015 challenge results
- 2015
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Ingår i: Proceedings 2015 IEEE International Conference on Computer Vision Workshops ICCVW 2015. - : IEEE. - 9780769557205 ; , s. 564-586
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website(1).
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- Li, Man-Bo, et al.
(författare)
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Amino-Supported Palladium Catalyst for Chemo- and Stereoselective Domino Reactions
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:2, s. 670-674
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Tidskriftsartikel (refereegranskat)abstract
- A solid amino-supported palladium catalyst is used in an oxidative domino reaction for the diastereoselective construction of alkyne-substituted cyclopentenol compounds. This heterogeneous catalyst exhibits high efficiency and excellent chemoselectivity, as well as good recyclability. The chemoselectivity of the domino reactions was readily controlled by switching the solvent and catalyst. Asymmetric syntheses and an oxidative carbocyclization-borylation reaction have also been developed based on the heterogeneous palladium catalyst.
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| 7. |
- Liang, Hua, et al.
(författare)
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Recognition of maturity-onset diabetes of the young in China
- 2021
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Ingår i: Journal of Diabetes Investigation. - : Wiley. - 2040-1116 .- 2040-1124. ; 12:4, s. 501-509
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Tidskriftsartikel (refereegranskat)abstract
- Aims/Introduction: Given that mutations related to maturity-onset diabetes of the young (MODY) are rarely found in Chinese populations, we aim to characterize the mutation spectrum of MODY pedigrees. Materials and Methods: Maturity-onset diabetes of the young candidate gene- or exome-targeted capture sequencing was carried out in 76 probands from unrelated families fulfilling the clinical diagnostic criteria for MODY. MAF <0.01 in the GnomAD or ExAC database was used to filter significant variants. Sanger sequencing was then carried out to validate findings. Function prediction by SIFT, PolyPhen-2 and PROVEAN or CADD was carried out in missense mutations. Results: A total of 32 mutations in six genes were identified in 31 families, accounting for 40.79% of the potential MODY families. The MODY subtype detection rate was 18.42% for GCK, 15.79% for HNF1A, 2.63% for HNF4A, and 1.32% for KLF11, PAX4 and NEUROG3. Seven nonsense/frameshift mutations and four missense mutations with damaging prediction were newly identified novel mutations. The clinical features of MODY2, MODY3/1 and MODYX are similar to previous reports. Clinical phenotype of NEUROG3 p.Arg55Glufs*23 is characterized by hyperglycemia and mild intermittent abdominal pain. Conclusions: This study adds to the emerging pattern of MODY epidemiology that the proportion of MODY explained by known pathogenic genes is higher than that previously reported, and found NEUROG3 as a new causative gene for MODY.
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| 9. |
- Prein, Andreas F., et al.
(författare)
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Towards Ensemble-Based Kilometer-Scale Climate Simulations over the Third Pole Region
- 2022
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Ingår i: Climate Dynamics. - : Springer Science and Business Media LLC. - 0930-7575 .- 1432-0894.
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Tidskriftsartikel (refereegranskat)abstract
- The Tibetan Plateau and its surrounding mountains have an average elevation of 4,400 m and a glaciated area of ∼ 100,000 km 2 giving it the name “Third Pole (TP) region”. The TP is the headwater of many major rivers in Asia that provide fresh water to hundreds of millions of people. Climate change is altering the energy and water cycle of the TP at a record pace but the future of this region is highly uncertain due to major challenges in simulating weather and climate processes in this complex area. The Convection-Permitting Third Pole (CPTP) project is a Coordinated Regional Downscaling Experiment (CORDEX) Flagship Pilot Study (FPS) that aims to revolutionize our understanding of climate change impacts on the TP through ensemble-based, kilometer-scale climate modeling. Here we present the experimental design and first results from multi-model, multi-physics ensemble simulations of three case studies. The five participating modeling systems show high performance across a range of meteorological situations and are close to having ”observational quality” in simulating precipitation and near-surface temperature. This is partly due to the large differences between observational datasets in this region, which are the leading source of uncertainty in model evaluations. However, a systematic cold bias above 2000 m exists in most modeling systems. Model physics sensitivity tests performed with the Weather Research and Forecasting (WRF) model show that planetary boundary layer (PBL) physics and microphysics contribute equally to model uncertainties. Additionally, larger domains result in better model performance. We conclude by describing high-priority research needs and the next steps in the CPTP project.
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| 10. |
- Qin, Yi, et al.
(författare)
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Structural and Functional Study of D-Glucuronyl C5-epimerase
- 2015
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 290:8, s. 4620-4630
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Tidskriftsartikel (refereegranskat)abstract
- Heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix, which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. D-Glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis, converting D-glucuronic acid to L-iduronic acid to increase HS flexibility. This modification of HS is important for protein ligand recognition. We have determined the crystal structures of Glce in apo-form (unliganded) and in complex with heparin hexasaccharide (product of Glce following O-sulfation), both in a stable dimer conformation. A Glce dimer contains two catalytic sites, each at a positively charged cleft in C-terminal alpha-helical domains binding one negatively charged hexasaccharide. Based on the structural and mutagenesis studies, three tyrosine residues, Tyr(468), Tyr(528), and Tyr(546), in the active site were found to be crucial for the enzymatic activity. The complex structure also reveals the mechanism of product inhibition (i.e. 2-O- and 6-O-sulfation of HS keeps the C5 carbon of L-iduronic acid away from the active-site tyrosine residues). Our structural and functional data advance understanding of the key modification in HS biosynthesis.
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