| 1. |
|
|
| 2. |
- Yang, Zhijian, et al.
(författare)
-
Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
-
Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
-
Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
|
|
| 3. |
- Brownstein, Catherine A., et al.
(författare)
-
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
|
|
| 4. |
|
|
| 5. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
-
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
|
|
| 6. |
- Lin, Yuze, et al.
(författare)
-
Balanced Partnership between Donor and Acceptor Components in Nonfullerene Organic Solar Cells with > 12% Efficiency
- 2018
-
Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 30:16
-
Tidskriftsartikel (refereegranskat)abstract
- Relative to electron donors for bulk heterojunction organic solar cells (OSCs), electron acceptors that absorb strongly in the visible and even near-infrared region are less well developed, which hinders the further development of OSCs. Fullerenes as traditional electron acceptors have relatively weak visible absorption and limited electronic tunability, which constrains the optical and electronic properties required of the donor. Here, high-performance fullerene-free OSCs based on a combination of a medium-bandgap polymer donor (FTAZ) and a narrow-bandgap nonfullerene acceptor (IDIC), which exhibit complementary absorption, matched energy levels, and blend with pure phases on the exciton diffusion length scale, are reported. The single-junction OSCs based on the FTAZ:IDIC blend exhibit power conversion efficiencies up to 12.5% with a certified value of 12.14%. Transient absorption spectroscopy reveals that exciting either the donor or the acceptor component efficiently generates mobile charges, which do not suffer from recombination to triplet states. Balancing photocurrent generation between the donor and nonfullerene acceptor removes undesirable constraints on the donor imposed by fullerene derivatives, opening a new avenue toward even higher efficiency for OSCs.
|
|
| 7. |
- Liu, Quanli, 1988, et al.
(författare)
-
Rewiring carbon metabolism in yeast for high level production of aromatic chemicals
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 10:1
-
Tidskriftsartikel (refereegranskat)abstract
- The production of bioactive plant compounds using microbial hosts is considered a safe, cost-competitive and scalable approach to their production. However, microbial production of some compounds like aromatic amino acid (AAA)-derived chemicals, remains an outstanding metabolic engineering challenge. Here we present the construction of a Saccharomyces cerevisiae platform strain able to produce high levels of p-coumaric acid, an AAA-derived precursor for many commercially valuable chemicals. This is achieved through engineering the AAA biosynthesis pathway, introducing a phosphoketalose-based pathway to divert glycolytic flux towards erythrose 4-phosphate formation, and optimizing carbon distribution between glycolysis and the AAA biosynthesis pathway by replacing the promoters of several important genes at key nodes between these two pathways. This results in a maximum p-coumaric acid titer of 12.5 g L−1 and a maximum yield on glucose of 154.9 mg g−1.
|
|
| 8. |
- Zhang, Lin, et al.
(författare)
-
Cr-promoted formation of B2+L21 composite nanoprecipitates and enhanced mechanical properties in ferritic alloy
- 2023
-
Ingår i: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 243
-
Tidskriftsartikel (refereegranskat)abstract
- The critical role of Cr on nanoprecipitates and the mechanical property of Fe-Ni-Al-Mn ferritic steel were systematically studied in this research. The two types of nanoprecipitates in the Cr added alloy were characterized through a combination of aberration-corrected scanning transmission electron microscopy and atom probe tomography techniques. The atomic-scale structure and chemistry analysis reveal that fine globular-shaped precipitates have a B2-structure, while coarse elongated precipitates have B2+L21 composite structures. The first-principles calculations reveal that the segregation of Cr at the L21/bcc interface reduces the interface and strain energy for the nucleation of the L21-type phase. With the increasing precipitate size, the B2 structure is gradually transformed to L21 to reduce elastic strain, thereby promoting the formation of B2+L21 composite nanoprecipitate. The addition of 10 wt% Cr results in an increase of ∼275 MPa in yield strength without obvious loss of ductility. The effect of Cr on the strength mechanisms were quantitatively analyzed, revealing that the strength of the ferritic alloy mainly improved by the formation of B2+L21 composite nanoprecipitate, which is more effective than solid solution strengthening.
|
|
| 9. |
- Brazel, David M., et al.
(författare)
-
Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use
- 2019
-
Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 85:11, s. 946-955
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.
|
|
| 10. |
- Chen, Ping, et al.
(författare)
-
A 12.4-day periodicity in a close binary system after a supernova
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 625:7994, s. 253-258
-
Tidskriftsartikel (refereegranskat)abstract
- Neutron stars and stellar-mass black holes are the remnants of massive star explosions1. Most massive stars reside in close binary systems2, and the interplay between the companion star and the newly formed compact object has been theoretically explored3, but signatures for binarity or evidence for the formation of a compact object during a supernova explosion are still lacking. Here we report a stripped-envelope supernova, SN 2022jli, which shows 12.4-day periodic undulations during the declining light curve. Narrow Hα emission is detected in late-time spectra with concordant periodic velocity shifts, probably arising from hydrogen gas stripped from a companion and accreted onto the compact remnant. A new Fermi-LAT γ-ray source is temporally and positionally consistent with SN 2022jli. The observed properties of SN 2022jli, including periodic undulations in the optical light curve, coherent Hα emission shifting and evidence for association with a γ-ray source, point to the explosion of a massive star in a binary system leaving behind a bound compact remnant. Mass accretion from the companion star onto the compact object powers the light curve of the supernova and generates the γ-ray emission.
|
|
| 11. |
- Chen, Wenbo, et al.
(författare)
-
The draft genome of whitefly Bemisia tabaci MEAM1, a global crop pest, provides novel insights into virus transmission, host adaptation, and insecticide resistance
- 2016
-
Ingår i: BMC Biology. - : Springer Science and Business Media LLC. - 1741-7007. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is among the 100 worst invasive species in the world. As one of the most important crop pests and virus vectors, B. tabaci causes substantial crop losses and poses a serious threat to global food security. Results: We report the 615-Mb high-quality genome sequence of B. tabaci Middle East-Asia Minor 1 (MEAM1), the first genome sequence in the Aleyrodidae family, which contains 15,664 protein-coding genes. The B. tabaci genome is highly divergent from other sequenced hemipteran genomes, sharing no detectable synteny. A number of known detoxification gene families, including cytochrome P450s and UDP-glucuronosyltransferases, are significantly expanded in B. tabaci. Other expanded gene families, including cathepsins, large clusters of tandemly duplicated B. tabaci-specific genes, and phosphatidylethanolamine-binding proteins (PEBPs), were found to be associated with virus acquisition and transmission and/or insecticide resistance, likely contributing to the global invasiveness and efficient virus transmission capacity of B. tabaci. The presence of 142 horizontally transferred genes from bacteria or fungi in the B. tabaci genome, including genes encoding hopanoid/sterol synthesis and xenobiotic detoxification enzymes that are not present in other insects, offers novel insights into the unique biological adaptations of this insect such as polyphagy and insecticide resistance. Interestingly, two adjacent bacterial pantothenate biosynthesis genes, panB and panC, have been co-transferred into B. tabaci and fused into a single gene that has acquired introns during its evolution. Conclusions: The B. tabaci genome contains numerous genetic novelties, including expansions in gene families associated with insecticide resistance, detoxification and virus transmission, as well as numerous horizontally transferred genes from bacteria and fungi. We believe these novelties likely have shaped B. tabaci as a highly invasive polyphagous crop pest and efficient vector of plant viruses. The genome serves as a reference for resolving the B. tabaci cryptic species complex, understanding fundamental biological novelties, and providing valuable genetic information to assist the development of novel strategies for controlling whiteflies and the viruses they transmit.
|
|
| 12. |
- Chen, Xin, 1980, et al.
(författare)
-
Dataset for suppressors of amyloid-beta toxicity and their functions in recombinant protein production in yeast
- 2022
-
Ingår i: Data in Brief. - : Elsevier BV. - 2352-3409. ; 42
-
Tidskriftsartikel (refereegranskat)abstract
- The production of recombinant proteins at high levels often induces stress-related phenotypes by protein misfolding or aggregation. These are similar to those of the yeast Alzheimer's disease (AD) model in which amyloid-beta peptides (A beta 42) were accumulated [1,2] . We have previously identified suppressors of A beta 42 cytotoxicity via the genome-wide synthetic genetic array (SGA) [3] and here we use them as metabolic engineering targets to evaluate their potentiality on recombinant protein production in yeast Saccharomyces cerevisiae. In order to investigate the mechanisms linking the genetic modifications to the improved recombinant protein production, we perform systems biology approaches (transcriptomics and proteomics) on the resulting strain and intermediate strains. The RNAseq data are preprocessed by the nf-core/RNAseq pipeline and analyzed using the Platform for Integrative Analysis of Omics (PIANO) package [4] . The quantitative proteome is analyzed on an Orbitrap Fusion Lumos mass spectrometer interfaced with an Easy-nLC1200 liquid chromatography (LC) system. LC-MS data files are processed by Proteome Discoverer version 2.4 with Mascot 2.5.1 as a database search engine. The original data presented in this work can be found in the research paper titled "Suppressors of Amyloid-beta Toxicity Improve Recombinant Protein Produc-tion in yeast by Reducing Oxidative Stress and Tuning Cellu-lar Metabolism", by Chen et al. [5] . (C) 2022 The Author(s). Published by Elsevier Inc.
|
|
| 13. |
- Chen, Xiaowei, et al.
(författare)
-
Do persuasive designs make smartphones more addictive? : A mixed-methods study on Chinese university students
- 2023
-
Ingår i: Computers in Human Behavior Reports. - : Elsevier BV. - 2451-9588. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Persuasive designs have become prevalent for smartphones, and an increasing number of users report problematic smartphone use behaviours. Persuasive designs in smartphones might be accountable for the development and reinforcement of such problematic use. This paper uses a mixed-methods approach to study the relationship between persuasive designs and problematic smartphone use: (1) questionnaires (N=183) to investigate the proportion of participants with multiple problematic smartphone use behaviours and smartphone designs and applications (apps) that they perceived affecting their attitudes and behaviours, and (2) interviews (N=10) to deepen our understanding of users’ observations and evaluations of persuasive designs. 25% of the participants self-reported having multiple problematic smartphone use behaviours, with short video, social networking, game and learning apps perceived as the most attitude- and behaviour-affecting. Interviewees identified multiple persuasive designs in most of these apps and stated that persuasive designs prolonged their screen time, reinforced phone-checking habits, and caused distractions. Overall, this study provides evidence to argue that persuasive designs contribute to problematic smartphone use, potentially making smartphones more addictive. We end our study by discussing the ethical implications of persuasive designs that became salient in our study.
|
|
| 14. |
- Chen, Xin, 1980, et al.
(författare)
-
FMN reduces Amyloid-beta toxicity in yeast by regulating redox status and cellular metabolism
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is defined by progressive neurodegeneration, with oligomerization and aggregation of amyloid-beta peptides (A beta) playing a pivotal role in its pathogenesis. In recent years, the yeast Saccharomyces cerevisiae has been successfully used to clarify the roles of different human proteins involved in neurodegeneration. Here, we report a genome-wide synthetic genetic interaction array to identify toxicity modifiers of A beta 42, using yeast as the model organism. We find that FMN1, the gene encoding riboflavin kinase, and its metabolic product flavin mononucleotide (FMN) reduce A beta 42 toxicity. Classic experimental analyses combined with RNAseq show the effects of FMN supplementation to include reducing misfolded protein load, altering cellular metabolism, increasing NADH/(NADH+NAD(+)) and NADPH/(NADPH+NADP(+)) ratios and increasing resistance to oxidative stress. Additionally, FMN supplementation modifies Htt103QP toxicity and alpha-synuclein toxicity in the humanized yeast. Our findings offer insights for reducing cytotoxicity of A beta 42, and potentially other misfolded proteins, via FMN-dependent cellular pathways.Saccharomyces cerevisiae is a model organism to study proteins involved in neurodegeneration. Here, the authors performed a yeast genome-wide synthetic genetic interaction array (SGA) to screen for toxicity modifiers of A beta 42 and identify riboflavin kinase and its metabolic product flavin mononucleotide as modulators that alleviate cellular A beta 42 toxicity, which is supported by further experimental analyses.
|
|
| 15. |
- Chen, Xin, 1980, et al.
(författare)
-
Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
- 2022
-
Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 72, s. 311-324
-
Tidskriftsartikel (refereegranskat)abstract
- High-level production of recombinant proteins in industrial microorganisms is often limited by the formation of misfolded proteins or protein aggregates, which consequently induce cellular stress responses. We hypothesized that in a yeast Alzheimer's disease (AD) model overexpression of amyloid-β peptides (Aβ42), one of the main peptides relevant for AD pathologies, induces similar phenotypes of cellular stress. Using this humanized AD model, we previously identified suppressors of Aβ42 cytotoxicity. Here we hypothesize that these suppressors could be used as metabolic engineering targets to alleviate cellular stress and improve recombinant protein production in the yeast Saccharomyces cerevisiae. Forty-six candidate genes were individually deleted and twenty were individually overexpressed. The positive targets that increased recombinant α-amylase production were further combined leading to an 18.7-fold increased recombinant protein production. These target genes are involved in multiple cellular networks including RNA processing, transcription, ER-mitochondrial complex, and protein unfolding. By using transcriptomics and proteomics analyses, combined with reverse metabolic engineering, we showed that reduced oxidative stress, increased membrane lipid biosynthesis and repressed arginine and sulfur amino acid biosynthesis are significant pathways for increased recombinant protein production. Our findings provide new insights towards developing synthetic yeast cell factories for biosynthesis of valuable proteins.
|
|
| 16. |
- Dabirian, Yasaman, 1992, et al.
(författare)
-
Expanding the Dynamic Range of a Transcription Factor-Based Biosensor in Saccharomyces cerevisiae
- 2019
-
Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 8:9, s. 1968-1975
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolite biosensors are useful tools for high-throughput screening approaches and pathway regulation approaches. An important feature of biosensors is the dynamic range. To expand the maximum dynamic range of a transcription factor-based biosensor in Saccharomyces cerevisiae, using the fapO/FapR system from Bacillus subtilis as an example case, five native promoters, including constitutive and glucose-regulated ones, were modified. By evaluating different binding site (BS) positions in the core promoters, we identified locations that resulted in a high maximum dynamic range with low expression under repressed conditions. We further identified BS positions in the upstream element region of the TEF1 promoter that did not influence the native promoter strength but resulted in repression in the presence of a chimeric repressor consisting of FapR and the yeast repressor Mig1. These modified promoters with broad dynamic ranges will provide useful information for the engineering of future biosensors and their use in complex genetic circuits.
|
|
| 17. |
- Dong, Bin, et al.
(författare)
-
Substrate-, Wavelength-, and Time-Dependent Plasmon-Assisted Surface Catalysis Reaction of 4-Nitrobenzenethiol Dimerizing to p,p '-Dimercaptoazobenzene on Au, Ag, and Cu Films
- 2011
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:17, s. 10677-10682
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, we experimentally investigate the substrate, wavelength, and time dependence of the plasmon-assisted surface-catalyzed dimerization of 4-nitrobenzenethiol to form p,p'-dimercaptoazobenzene on Au, Ag, and Cu films. We provide direct experimental evidence that surface plasmon resonance plays the most important role in these surface-catalyzed reactions. It is found that the reaction is strongly dependent on the substrate, the wavelength of the laser, and the reaction timescales. Our experimental results revealed that optimal experimental conditions can be rationally chosen to control (accelerate or restrain) this reaction. The experimental results are also confirmed by theoretical calculations.
|
|
| 18. |
- Fu, Jianxin, et al.
(författare)
-
Loss of intestinal core 1-derived O-glycans causes spontaneous colitis in mice.
- 2011
-
Ingår i: The Journal of clinical investigation. - 1558-8238. ; 121:4, s. 1657-66
-
Tidskriftsartikel (refereegranskat)abstract
- Mucin-type O-linked oligosaccharides (O-glycans) are primary components of the intestinal mucins that form the mucus gel layer overlying the gut epithelium. Impaired expression of intestinal O-glycans has been observed in patients with ulcerative colitis (UC), but its role in the etiology of this disease is unknown. Here, we report that mice with intestinal epithelial cell-specific deficiency of core 1-derived O-glycans, the predominant form of O-glycans, developed spontaneous colitis that resembled human UC, including massive myeloid infiltrates and crypt abscesses. The colitis manifested in these mice was also characterized by TNF-producing myeloid infiltrates in colon mucosa in the absence of lymphocytes, supporting an essential role for myeloid cells in colitis initiation. Furthermore, induced deletion of intestinal core 1-derived O-glycans caused spontaneous colitis in adult mice. These data indicate a causal role for the loss of core 1-derived O-glycans in colitis. Finally, we detected a biosynthetic intermediate typically exposed in the absence of core 1 O-glycan, Tn antigen, in the colon epithelium of a subset of UC patients. Somatic mutations in the X-linked gene that encodes core 1 β1,3-galactosyltransferase-specific chaperone 1 (C1GALT1C1, also known as Cosmc), which is essential for core 1 O-glycosylation, were found in Tn-positive epithelia. These data suggest what we believe to be a new molecular mechanism for the pathogenesis of UC.
|
|
| 19. |
- Guan, Xiaowei, et al.
(författare)
-
Ultrasmall Directional Coupler and Disk-resonantor Based on Nano-scale Silicon Hybrid Plasmonic Waveguides
- 2012
-
Ingår i: 2012 Asia Communications And Photonics Conference (ACP). - Washington, D.C. : OSA. - 9781467362740 ; , s. AS2H.4-
-
Konferensbidrag (refereegranskat)abstract
- Nanophotonic integrated devices based on nano-scale silicon hybrid plasmonic waveguides have been demonstrated experimentally, including directional couplers and disk-resonators. The temperature-dependence of the hybrid plasmonic disk-resonators is also characterized.
|
|
| 20. |
- Huang, Ke, et al.
(författare)
-
The confounding effect of snow cover on assessing spring phenology from space : A new look at trends on the Tibetan Plateau
- 2021
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 756
-
Tidskriftsartikel (refereegranskat)abstract
- The Tibetan Plateau is the highest and largest plateau in the world, hosting unique alpine grassland and having a much higher snow cover than any other region at the same latitude, thus representing a “climate change hot-spot”. Land surface phenology characterizes the timing of vegetation seasonality at the per-pixel level using remote sensing systems. The impact of seasonal snow cover variations on land surface phenology has drawn much attention; however, there is still no consensus on how the remote sensing estimated start of season (SOS) is biased by the presence of preseason snow cover. Here, we analyzed SOS assessments from time series of satellite derived vegetation indices and solar-induced chlorophyll fluorescence (SIF) during 2003–2016 for the Tibetan Plateau. We evaluated satellite-based SOS with field observations and gross primary production (GPP) from eddy covariance for both snow-free and snow covered sites. SOS derived from SIF was highly correlated with field data (R2 = 0.83) and also the normalized difference phenology index (NDPI) performed well for both snow free (R2 = 0.77) and snow covered sites (R2 = 0.73). On the contrary, normalized difference vegetation index (NDVI) correlates only weakly with field data (R2 = 0.35 for snow free and R2 = 0.15 for snow covered sites). We further found that an earlier end of the snow season caused an earlier estimate of SOS for the Tibetan Plateau from NDVI as compared to NDPI. Our research therefore adds new evidence to the ongoing debate supporting the view that the claimed advance in land surface SOS over the Tibetan Plateau is an artifact from snow cover changes. These findings improve our understanding of the impact of snow on land surface phenology in alpine ecosystems, which can further improve remote sensing based land surface phenology assessments in snow-influenced ecosystems.
|
|
| 21. |
- Justice, Anne E., et al.
(författare)
-
Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
-
Tidskriftsartikel (refereegranskat)abstract
- Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
|
|
| 22. |
- Li, Xiaowei, et al.
(författare)
-
Harnessing xylose pathways for biofuels production
- 2019
-
Ingår i: Current Opinion in Biotechnology. - : Elsevier BV. - 0958-1669 .- 1879-0429. ; 57, s. 56-65
-
Forskningsöversikt (refereegranskat)abstract
- Energy security, environmental pollution, and economic development drive the development of alternatives to fossil fuels as an urgent global priority. Lignocellulosic biomass has the potential to contribute to meeting the demand for biofuel production via hydrolysis and fermentation of released sugars, such as glucose, xylose, and arabinose. Construction of robust cell factories requires introducing and rewiring of their metabolism to efficiently use all these sugars. Here, we review recent advances in re-constructing pathways for metabolism of pentoses, with special focus on xylose metabolism in the most widely used cell factories Saccharomyces cerevisiae and Escherichia coli. We also highlight engineering advanced biofuels-synthesis pathways and describes progress toward overcoming the challenges facing adoption of large-scale biofuel production.
|
|
| 23. |
- Li, Xiaowei, 1986, et al.
(författare)
-
Metabolic network remodelling enhances yeast’s fitness on xylose using aerobic glycolysis
- 2021
-
Ingår i: Nature Catalysis. - : Springer Science and Business Media LLC. - 2520-1158. ; 4:9, s. 783-796
-
Tidskriftsartikel (refereegranskat)abstract
- The reprogramming of metabolism in response to switching the carbon source from glucose to non-preferred carbon sources is well-studied for yeast. However, understanding how metabolic networks respond to utilize a non-natural carbon source such as xylose is limited due to the incomplete knowledge of cellular response mechanisms. Here we applied a combination of metabolic engineering, systems biology and adaptive laboratory evolution to gain insights into how yeast can perform a global rewiring of cellular processes to efficiently accompany metabolic transitions. Through metabolic engineering, we substantially enhanced the cell growth on xylose after the growth on glucose. Transcriptome analysis of the engineered strains demonstrated that multiple pathways were involved in the cellular reprogramming. Through genome resequencing of the evolved strains and reverse engineering, we further identified that SWI/SNF chromatin remodelling, osmotic response and aldehyde reductase were responsible for the improved growth. Combined, our analysis showed that glycerol-3-phosphate and xylitol serve as two key metabolites that affect cellular adaptation to growth on xylose. [Figure not available: see fulltext.].
|
|
| 24. |
- Lin, Yuze, et al.
(författare)
-
Mapping Polymer Donors toward High-Efficiency Fullerene Free Organic Solar Cells
- 2017
-
Ingår i: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 29:3
-
Tidskriftsartikel (refereegranskat)abstract
- Five polymer donors with distinct chemical structures and different electronic properties are surveyed in a planar and narrow-bandgap fused-ring electron acceptor (IDIC)-based organic solar cells, which exhibit power conversion efficiencies of up to 11%.
|
|
| 25. |
- Ma, Tian, et al.
(författare)
-
Lipid engineering combined with systematic metabolic engineering of Saccharomyces cerevisiae for high-yield production of lycopene
- 2019
-
Ingår i: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 52, s. 134-142
-
Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is an efficient host for natural-compound production and preferentially employed in academic studies and bioindustries. However, S. cerevisiae exhibits limited production capacity for lipophilic natural products, especially compounds that accumulate intracellularly, such as polyketides and carotenoids, with some engineered compounds displaying cytotoxicity. In this study, we used a nature-inspired strategy to establish an effective platform to improve lipid oil–triacylglycerol (TAG) metabolism and enable increased lycopene accumulation. Through systematic traditional engineering methods, we achieved relatively high-level production at 56.2 mg lycopene/g cell dry weight (cdw). To focus on TAG metabolism in order to increase lycopene accumulation, we overexpressed key genes associated with fatty acid synthesis and TAG production, followed by modulation of TAG fatty acyl composition by overexpressing a fatty acid desaturase (OLE1) and deletion of Seipin (FLD1), which regulates lipid-droplet size. Results showed that the engineered strain produced 70.5 mg lycopene/g cdw, a 25% increase relative to the original high-yield strain, with lycopene production reaching 2.37 g/L and 73.3 mg/g cdw in fed-batch fermentation and representing the highest lycopene yield in S. cerevisiae reported to date. These findings offer an effective strategy for extended systematic metabolic engineering through lipid engineering.
|
|
| 26. |
- Ma, Zhuo, et al.
(författare)
-
Deciphering early human pancreas development at the single-cell level
- 2023
-
Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding pancreas development can provide clues for better treatments of pancreatic diseases. However, the molecular heterogeneity and developmental trajectory of the early human pancreas are poorly explored. Here, we performed large-scale single-cell RNA sequencing and single-cell assay for transposase accessible chromatin sequencing of human embryonic pancreas tissue obtained from first-trimester embryos. We unraveled the molecular heterogeneity, developmental trajectories and regulatory networks of the major cell types. The results reveal that dorsal pancreatic multipotent cells in humans exhibit different gene expression patterns than ventral multipotent cells. Pancreato-biliary progenitors that generate ventral multipotent cells in humans were identified. Notch and MAPK signals from mesenchymal cells regulate the differentiation of multipotent cells into trunk and duct cells. Notably, we identified endocrine progenitor subclusters with different differentiation potentials. Although the developmental trajectories are largely conserved between humans and mice, some distinct gene expression patterns have also been identified. Overall, we provide a comprehensive landscape of early human pancreas development to understand its lineage transitions and molecular complexity. Here, the authors revealed molecular heterogeneity, developmental trajectory and regulatory network of early human pancreas development, and depict the whole progression of pancreatic organogenesis during the first trimester at the single-cell level.
|
|
| 27. |
- Mao, Jiwei, 1990, et al.
(författare)
-
Fine-tuning of p-coumaric acid synthesis to increase (2S)-naringenin production in yeast
- 2023
-
Ingår i: Metabolic Engineering. - 1096-7176 .- 1096-7184. ; 79, s. 192-202
-
Tidskriftsartikel (refereegranskat)abstract
- (2S)-Naringenin is a key precursor for biosynthesis of various high-value flavonoids and possesses a variety of nutritional and pharmaceutical properties on human health. Systematic optimization approaches have been employed to improve (2S)-naringenin production in different microbial hosts. However, very few studies have focused on the spatiotemporal distribution of (2S)-naringenin and the related pathway intermediate p-coumaric acid, which is an important factor for efficient production. Here, we first optimized the (2S)-naringenin biosynthetic pathway by alleviating the bottleneck downstream of p-coumaric acid and increasing malonyl-CoA supply, which improved (2S)-naringenin production but significant accumulation of p-coumaric acid still existed extracellularly. We thus established a dual dynamic control system through combining a malonyl-CoA biosensor regulator and an RNAi strategy, to autonomously control the synthesis of p-coumaric acid with the supply of malonyl-CoA. Furthermore, screening potential transporters led to identification of Pdr12 for improved (2S)-naringenin production and reduced accumulation of p-coumaric acid. Finally, a titer of 2.05 g/L (2S)-naringenin with negligible accumulation of p-coumaric acid was achieved in a fed batch fermentation. Our work highlights the importance of systematic control of pathway intermediates for efficient microbial production of plant natural products.
|
|
| 28. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 29. |
- Ong, Kwok Leung, et al.
(författare)
-
Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease : pooled analysis of 19 cohorts
- 2023
-
Ingår i: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 380
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived a linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD).DESIGN: Pooled analysis.DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020.STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate.DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis.MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/ min/1.73 m(2). In a sensitivity analysis, incident CKD was defined as new onset estimated glomerular filtration rate <60 mL/min/1.73 m(2) and <75% of baseline rate.RESULTS: 25 570 participants were included in the primary outcome analysis and 4944 (19.3%) developed incident CKD during follow-up (weighted median 11.3 years). In multivariable adjusted models, higher levels of total seafood n-3 PUFAs were associated with a lower incident CKD risk (relative risk per interquintile range 0.92, 95% confidence interval 0.86 to 0.98; P=0.009, I-2=9.9%). In categorical analyses, participants with total seafood n-3 PUFA level in the highest fifth had 13% lower risk of incident CKD compared with those in the lowest fifth (0.87, 0.80 to 0.96; P=0.005, I-2=0.0%). Plant derived a linolenic acid levels were not associated with incident CKD (1.00, 0.94 to 1.06; P=0.94, I-2=5.8%). Similar results were obtained in the sensitivity analysis. The association appeared consistent across subgroups by age (=60 v <60 years), estimated glomerular filtration rate (60-89 v =90 mL/min/1.73 m(2)), hypertension, diabetes, and coronary heart disease at baseline.CONCLUSIONS: Higher seafood derived n-3 PUFA levels were associated with lower risk of incident CKD, although this association was not found for plant derived n-3 PUFAs. These results support a favourable role for seafood derived n-3 PUFAs in preventing CKD.
|
|
| 30. |
- Pedroza, Gabriel, et al.
(författare)
-
The IJCAI-23 joint workshop on artificial intelligence safety and safe reinforcement learning (AISafety-SafeRL2023)
- 2023
-
Ingår i: Proceedings of the IJCAI-23 joint workshop on artificial intelligence safety and safe reinforcement learning (AISafety-SafeRL 2023) co-located with the 32nd international joint conference on artificial intelligence (IJACAI2023). - : CEUR-WS.
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- We summarize the IJCAI-23 Joint Workshop on Artificial Intelligence Safety and Safe Reinforcement Learning (AISafety-SafeRL2023)1, held at the 32nd International Joint Conference on Artificial Intelligence (IJCAI-23) on August 21-22, 2023 in Macau, China.
|
|
| 31. |
- Pereira, Rui, 1986, et al.
(författare)
-
Metabolic Engineering of Yeast
- 2021
-
Ingår i: Metabolic Engineering: Concepts and Applications: Volume 13a and 13b. - : Wiley. ; 13, s. 689-733
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter focuses on a few examples that can serve as illustrations of how powerful yeast metabolic engineering stands today. Yeast, especially S. cerevisiae, plays an essential role in bioethanol production. Rapid ethanol production by yeast cells makes the fermentation process less susceptible to contamination. Higher alcohols are attractive due to some advantages compared with bioethanol, such as higher energy density, better blending into gasoline, higher octane value, lower hygroscopicity, and less corrosivity. The ethanol production process in the industry is mainly achieved through simultaneous saccharification and fermentation. Production of insulin, by volume the largest pharmaceutical protein produced, has paved the way for a wide use of S. cerevisiae for production of recombinant proteins. Virus like particles are proteins of virus capsid, which are produced by recombinant DNA technology and are important for the development of viral vaccines as they can self-assemble and display similar immunogenic properties as native viruses.
|
|
| 32. |
- Qiang, Mingrui, et al.
(författare)
-
Late Quaternary Dust, Loess and Desert Dynamics in Upwind Areas of the Chinese Loess Plateau
- 2021
-
Ingår i: Frontiers in Earth Science. - : Frontiers Media S.A.. - 2296-6463. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- As a key global climate and dust archive, the nature of Chinese loess generation, transport and deposition remains debated. The lack of consensus on dust dynamics from sources to leeward regions fundamentally limits interpretation of the preserved past climate and dust record. Here, we investigate chronostratigraphic variability of aeolian deposits in upwind regions of the modern Chinese Loess Plateau (CLP) and attempt to understand dust dynamics that potentially affects loess deposition downwind. The strata consist of alternating layers of typical loess, well-sorted sand, and sandy loess, with obvious unconformities occurring at the transitions from loess to sand. We suggest that pre-existing typical loess in regions to the northwest of the modern CLP was eroded by wind, providing a significant source of homogeneous dust for the dust deposits downwind. The sand deposits interbedded with typical loess at the study sites suggests that proximal deserts have greatly expanded and contracted repeatedly prior to the Holocene. However, the spatial extents of the deserts, as inferred from the sections here, have not markedly diminished after the major expansion during the Last Glacial Maximum. Such a pattern of proximal desert dynamics plays an important role in regulating dust emission and transport, strongly affecting dust sequences on the CLP. Our results suggest a complex scenario of dust dynamics in upwind regions of the CLP at least over the Late Quaternary; the involved processes have to be considered when using conventional proxies from Chinese loess deposits to recover the history of climate and dust changes.
|
|
| 33. |
- Qin, Ning, et al.
(författare)
-
Rewiring Central Carbon Metabolism Ensures Increased Provision of Acetyl-CoA and NADPH Required for 3-OH-Propionic Acid Production
- 2020
-
Ingår i: ACS Synthetic Biology. - : American Chemical Society (ACS). - 2161-5063. ; 9:12, s. 3236-3244
-
Tidskriftsartikel (refereegranskat)abstract
- The central carbon metabolite acetyl-CoA and the cofactor NADPH are important for the synthesis of a wide array of biobased products. Here, we constructed a platform yeast strain for improved provision of acetyl-CoA and NADPH, and used the production of 3-hydroxypropionic acid (3-HP) as a case study. We first demonstrated that the integration of phosphoketolase and phosphotransacetylase improved 3-HP production by 41.9% and decreased glycerol production by 48.1% compared with that of the control strain. Then, to direct more carbon flux toward the pentose phosphate pathway, we reduced the expression of phosphoglucose isomerase by replacing its native promoter with a weaker promoter, and increased the expression of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase by replacing their native promoters with stronger promoters. This further improved 3-HP production by 26.4%. Furthermore, to increase the NADPH supply we overexpressed cytosolic aldehyde dehydrogenase, and improved 3-HP production by another 10.5%. Together with optimizing enzyme expression of acetyl-CoA carboxylase and malonyl-CoA reductase, the final strain is able to produce 3-HP with a final titer of 864.5 mg/L, which is a more than 24-fold improvement compared with that of the starting strain. Our strategy combines the PK pathway with the oxidative pentose phosphate pathway for the efficient provision of acetyl-CoA and NADPH, which provides both a higher theoretical yield and overall yield than the reported yeast-based 3-HP production strategies via the malonyl-CoA reductase-dependent pathway and sheds light on the construction of efficient platform cell factories for other products.
|
|
| 34. |
|
|
| 35. |
- Shi, Haonan, et al.
(författare)
-
Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities : a cross-sectional study with interrupted time series analysis
- 2023
-
Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia.Methods: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019.Results: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding & GE; 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) & GE; 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0. 87-0.97; p = 0.0019), duration of breastfeeding & GE; 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001).Conclusions: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.
|
|
| 36. |
- Sun, Mengtao, et al.
(författare)
-
The pH-Controlled Plasmon-Assisted Surface Photocatalysis Reaction of 4-Aminothiophenol to p,p '-Dimercaptoazobenzene on Au, Ag, and Cu Colloids
- 2011
-
Ingår i: Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 115:19, s. 9629-9636
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper, we report experimentally and theoretically a surface photocatalysis reaction of 4-aminothiophenol (PATP) to p,p'-dimercaptoazobenzene (DMAB) on Au, Ag, and Cu colloids. Surface enhanced Raman scattering (SEAS) spectra of PATP on Au and Cu colloids are significantly different from the normal Raman spectrum of PATP powder. Quantum chemical calculations reveal that PATP on Au and Cu colloids is converted to DMAB by a surface photocatalysis reaction, and all the strongly enhanced Raman peaks are the symmetric Ag vibrational mode by surface plasmon. The pH value effects on surface photocatalysis reaction were also investigated experimentally. It is found that plasmon-assisted surface photocatalysis reaction can be efficiently controlled by different pH values. The possibility of protonation of PATP adsorbed on Au and Ag nanoparticles at pH 3 is investigated theoretically. The molecular mechanism is proposed for controlling surface photocatalysis reaction by pH values.
|
|
| 37. |
- Tian, Chen, et al.
(författare)
-
Functional Failure Behavior of Submerged Entry Nozzle during the Continuous Casting Process of the Bearing Steel GCr15
- 2024
-
Ingår i: Steel Research International. - : John Wiley & Sons. - 1611-3683 .- 1869-344X. ; 95:8
-
Tidskriftsartikel (refereegranskat)abstract
- The submerged entry nozzle (SEN) is an indispensable functional structural ceramic in the current continuous casting production. The stability and safety of the SEN is very important during the casting process. In this article, the functional failure of the SEN during the continuous casting process of the bearing steel GCr15 is studied. The results show that the functional failure of the SEN during the bearing steel GCr15 casting process is caused by the clogging inside the SEN which is led by the low cleanliness and the high impurities n the molten steel. The clogging in the SEN can be divided into solidified steel area, loose area, dense area, and surface area. To improve the castability of bearing steel or other high-cleanliness steel, it is necessary to strengthen the refining process and treatment effect, strengthen the sealing and the effect of the protective casting of the molten steel, and moderate optimization of nozzle materials or the application of external fields on the SEN.
|
|
| 38. |
- Turcot, Valerie, et al.
(författare)
-
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
|
|
| 39. |
- Wang, Yanyan, 1989, et al.
(författare)
-
CRISPR/Cas9-mediated point mutations improve alpha-amylase secretion in Saccharomyces cerevisiae
- 2022
-
Ingår i: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 22:1
-
Tidskriftsartikel (refereegranskat)abstract
- The rapid expansion of the application of pharmaceutical proteins and industrial enzymes requires robust microbial workhorses for high protein production. The budding yeast Saccharomyces cerevisiae is an attractive cell factory due to its ability to perform eukaryotic post-translational modifications and to secrete proteins. Many strategies have been used to engineer yeast platform strains for higher protein secretion capacity. Herein, we investigated a line of strains that have previously been selected after UV random mutagenesis for improved alpha-amylase secretion. A total of 42 amino acid altering point mutations identified in this strain line were reintroduced into the parental strain AAC to study their individual effects on protein secretion. These point mutations included missense mutations (amino acid substitution), nonsense mutations (stop codon generation), and frameshift mutations. For comparison, single gene deletions for the corresponding target genes were also performed in this study. A total of 11 point mutations and seven gene deletions were found to effectively improve alpha-amylase secretion. These targets were involved in several bioprocesses, including cellular stresses, protein degradation, transportation, mRNA processing and export, DNA replication, and repair, which indicates that the improved protein secretion capacity in the evolved strains is the result of the interaction of multiple intracellular processes. Our findings will contribute to the construction of novel cell factories for recombinant protein secretion. Systematic characterization of point mutations from evolved strains using CRISPR/Cas9 technology revealed a set of gene alterations that improved recombinant protein secretion in Saccharomyces cerevisiae.
|
|
| 40. |
- Wang, Yanyan, 1989, et al.
(författare)
-
Expression of antibody fragments in Saccharomyces cerevisiae strains evolved for enhanced protein secretion
- 2021
-
Ingår i: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Monoclonal antibodies, antibody fragments and fusion proteins derived thereof have revolutionized the practice of medicine. Major challenges faced by the biopharmaceutical industry are however high production costs, long processing times and low productivities associated with their production in mammalian cell lines. The yeast Saccharomyces cerevisiae, a well-characterized eukaryotic cell factory possessing the capacity of posttranslational modifications, has been industrially exploited as a secretion host for production of a range of products, including pharmaceuticals. However, due to the incompatible surface glycosylation, few antibody molecules have been functionally expressed in S. cerevisiae. Here, three non-glycosylated antibody fragments from human and the Camelidae family were chosen for expression in a S. cerevisiae strain (HA) previously evolved for high α-amylase secretion. These included the Fab fragment Ranibizumab (Ran), the scFv peptide Pexelizumab (Pex), and a nanobody consisting of a single V-type domain (Nan). Both secretion and biological activities of the antibody fragments were confirmed. In addition, the secretion level of each protein was compared in the wild type (LA) and two evolved strains (HA and MA) with different secretory capacities. We found that the secretion of Ran and Nan was positively correlated with the strains’ secretory capacity, while Pex was most efficiently secreted in the parental strain. To investigate the mechanisms for different secretion abilities in these selected yeast strains for the different antibody fragments, RNA-seq analysis was performed. The results showed that several bioprocesses were significantly enriched for differentially expressed genes when comparing the enriched terms between HA.Nan vs. LA.Nan and HA.Pex vs. LA.Pex, including amino acid metabolism, protein synthesis, cell cycle and others, which indicates that there are unique physiological needs for each antibody fragment secretion.
|
|
| 41. |
- Wang, Ziming, 1992, et al.
(författare)
-
Exploring Intended Functions of Indoor Flying Robots Interacting With Humans in Proximity
- 2024
-
Ingår i: Conference on Human Factors in Computing Systems - Proceedings.
-
Konferensbidrag (refereegranskat)abstract
- What will people experience when drones become common in home environments? How will their functions and distances impact human experiences? To explore the potential usage of indoor drones, we conducted a mixed-methods study (N=60) on the reported perceptions of a small flying robot. We employed a factorial experimental design, involving four intended drone functions (camera, education, pet, unknown) at two distances (near, far). Our findings suggest that intended functions significantly influence participants' perceptions. Among the functions examined, participants found the camera useful but annoying, and the pet useless but pleasant. The education emerged as the most favored function, while the unknown function was the least preferred one. Based on these findings, we discuss implications for designing positive interactions between humans and indoor drones, considering aspects such as context, transparency, privacy, technical factors, and personalization.
|
|
| 42. |
- Zhan, Chunjun, 1986, et al.
(författare)
-
Reprogramming methanol utilization pathways to convert Saccharomyces cerevisiae to a synthetic methylotroph
- 2023
-
Ingår i: Nature Catalysis. - 2520-1158. ; 6:5, s. 435-450
-
Tidskriftsartikel (refereegranskat)abstract
- Methanol, an organic one-carbon (C1) compound, represents an attractive alternative carbon source for microbial fermentation. Despite considerable advancements in methanol utilization by prokaryotes such as Escherichia coli, engineering eukaryotic model organisms such as Saccharomyces cerevisiae into synthetic methylotrophs remains challenging. Here, an engineered module circuit strategy combined with adaptive laboratory evolution was applied to engineer S. cerevisiae to use methanol as the sole carbon source. We revealed that the evolved glyoxylate-based serine pathway plays an important role in methanol-dependent growth by promoting formaldehyde assimilation. Further, we determined that the isoprenoid biosynthetic pathway was upregulated, resulting in an increased concentration of squalene and ergosterol in our evolved strain. These changes could potentially alleviate cell membrane damage in the presence of methanol. This work sets the stage for expanding the potential of exploiting S. cerevisiae as a potential organic one-carbon platform for biochemical or biofuel production. [Figure not available: see fulltext.].
|
|
| 43. |
- Zhan, Chunjun, 1986, et al.
(författare)
-
Strategies and challenges with the microbial conversion of methanol to high-value chemicals
- 2021
-
Ingår i: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 118:10, s. 3655-3668
-
Forskningsöversikt (refereegranskat)abstract
- As alternatives to traditional fermentation substrates, methanol (CH3OH), carbon dioxide (CO2) and methane (CH4) represent promising one-carbon (C1) sources that are readily available at low-cost and share similar metabolic pathway. Of these C1 compounds, methanol is used as a carbon and energy source by native methylotrophs, and can be obtained from CO2 and CH4 by chemical catalysis. Therefore, constructing and rewiring methanol utilization pathways may enable the use of one-carbon sources for microbial fermentations. Recent bioengineering efforts have shown that both native and nonnative methylotrophic organisms can be engineered to convert methanol, together with other carbon sources, into biofuels and other commodity chemicals. However, many challenges remain and must be overcome before industrial-scale bioprocessing can be established using these engineered cell refineries. Here, we provide a comprehensive summary and comparison of methanol metabolic pathways from different methylotrophs, followed by a review of recent progress in engineering methanol metabolic pathways in vitro and in vivo to produce chemicals. We discuss the major challenges associated with establishing efficient methanol metabolic pathways in microbial cells, and propose improved designs for future engineering.
|
|
| 44. |
- Zuo, Xiao, et al.
(författare)
-
Discharge state transition and cathode fall thickness evolution during chromium HiPIMS discharge
- 2017
-
Ingår i: Physics of Plasmas. - : AMER INST PHYSICS. - 1070-664X .- 1089-7674. ; 24:8
-
Tidskriftsartikel (refereegranskat)abstract
- The temporal evolutions of target voltage and current waveforms under different pulse voltage and working pressure conditions were studied during Cr high power impulse magnetron sputtering discharges. Target voltage and current characteristics demonstrated that when the pulse width was set as 200 mu s, HiPIMS discharge went through a four-stage sequence during each pulse, Townsend discharge, glow discharge, afterglow, and pulse-off stages. A discharge state transition in the glow discharge stage happened at high pulse voltage and working pressure conditions. Furthermore, the dependence of reduced cathode fall thickness pdcon pulse voltage, working pressure, and normalized current density j/p(2) was presented. It was found that gas rarefaction leads to a change of relationship between pd(c) and j/p(2). A noticeable increase of the cathode fall thickness caused by gas rarefaction has been found. Published by AIP Publishing.
|
|
