| 1. |
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| 2. |
- Marouli, Eirini, et al.
(author)
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Rare and low-frequency coding variants alter human adult height
- 2017
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Journal article (peer-reviewed)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.
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| 3. |
- Turcot, Valerie, et al.
(author)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Journal article (peer-reviewed)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.
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| 4. |
- Justice, Anne E., et al.
(author)
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Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
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Journal article (peer-reviewed)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.
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| 5. |
- Zhan, Chunjun, 1986, et al.
(author)
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Reprogramming methanol utilization pathways to convert Saccharomyces cerevisiae to a synthetic methylotroph
- 2023
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In: Nature Catalysis. - 2520-1158. ; 6:5, s. 435-450
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Journal article (peer-reviewed)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.].
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| 6. |
- Brownstein, Catherine A., et al.
(author)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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In: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Journal article (peer-reviewed)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.
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| 7. |
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| 8. |
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| 9. |
- Li, Xi, et al.
(author)
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MicroRNA-132 with Therapeutic Potential in Chronic Wounds.
- 2017
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 137:12, s. 2630-2638
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Journal article (peer-reviewed)abstract
- Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search toward more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared with normal skin wounds and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared with wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound edge keratinocytes and reduced inflammation. The pro-healing effect of miR-132 was further supported by global transcriptome analysis, which showed that several inflammation-related signaling pathways (e.g., NF-κB, NOD-like receptor, toll-like receptor, and tumor necrosis factor signaling pathways) were the top ones regulated by miR-132 in vivo. Moreover, we topically applied liposome-formulated miR-132 mimics mixed with pluronic F-127 gel on human ex vivo skin wounds, which promoted re-epithelialization. Together, our study showed the therapeutic potential of miR-132 in chronic wounds, which warrants further evaluation in controlled clinical trials.
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| 10. |
- Shi, Haonan, et al.
(author)
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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
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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21
-
Journal article (peer-reviewed)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.
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| 11. |
- Wang, Renjun, et al.
(author)
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Sympathoexcitation in Rats With Chronic Heart Failure Depends on Homeobox D10 and MicroRNA-7b Inhibiting GABBR1 Translation in Paraventricular Nucleus
- 2016
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In: Circulation Heart Failure. - 1941-3289 .- 1941-3297. ; 9:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Chronic heart failure (CHF) increases sympathoexcitation through angiotensin II (ANG II) receptors (AT1R) in the paraventricular nucleus (PVN). Recent publications indicate both γ-aminobutyric acid B-type receptor 1 (GABBR1) and microRNA-7b (miR-7b) are expressed in the PVN. We hypothesized that ANG II regulates sympathoexcitation through homeobox D10 (HoxD10), which regulates miR-7b in other tissues.METHODS AND RESULTS: Ligation of the left anterior descendent coronary artery in rats caused CHF and sympathoexcitation. PVN expression of AT1R, HoxD10, and miR-7b was increased, whereas GABBR1 was lower in CHF. Infusion of miR-7b in the PVN caused sympathoexcitation in control animals and enhanced the changes in CHF. Antisense miR-7b infused in PVN normalized GABBR1 expression while attenuating CHF symptoms, including sympathoexcitation. A luciferase reporter assay detected miR-7b binding to the 3' untranslated region of GABBR1 that was absent after targeted mutagenesis. ANG II induced HoxD10 and miR-7b in NG108 cells, effects blocked by AT1R blocker losartan and by HoxD10 silencing. miR-7b transfection into NG108 cells decreased GABBR1 expression, which was inhibited by miR-7b antisense. In vivo PVN knockdown of AT1R attenuated the symptoms of CHF, whereas HoxD10 overexpression exaggerated them. Finally, in vivo PVN ANG II infusion caused dose-dependent sympathoexcitation that was abrogated by miR-7b antisense and exaggerated by GABBR1 silencing.CONCLUSIONS: There is an ANG II/AT1R/HoxD10/miR-7b/GABBR1 pathway in the PVN that contributes to sympathoexcitation and deterioration of cardiac function in CHF.
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| 12. |
- Wang, Yilin, et al.
(author)
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Interrupted silicogermanate with 10-ring channels : synthesis and structure determination by combining rotation electron diffraction and powder X-ray diffraction
- 2017
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In: Inorganic Chemistry Frontiers. - 2052-1545 .- 2052-1553. ; 4:10, s. 1654-1659
-
Journal article (peer-reviewed)abstract
- Silicogermanate (JU110) with an interrupted open-framework has been synthesized by using a hydrothermal method using 1,1′-(1,4-phenylenebis(methylene))bis(1-methylpyrrolidin-1-ium) hydroxide as an organic structure-directing agent (OSDA). Silicon and fluoride anions were introduced to the concentrated-gel synthesis system, and different synthetic parameters influencing the synthesis were discussed. The structure of JU110 was characterised by using rotation electron diffraction (RED) and high-resolution powder X-ray diffraction. JU110 crystallizes in the space group Fm2m (No. 42) with a = 13.9117(2) Å, b = 18.2980(3) Å and c = 32.7800(6) Å. The structure is constructed by the sti layers found in the STI framework that are pillared by D4R/Ge7 units to form a large cavity, showing 10-ring openings along [100] and 9-ring openings along [110]. Thermal stability studies showed that the framework was maintained with the loss of water molecules, but collapsed with the removal of charge-compensating cations.
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| 13. |
- Xu, Husen, et al.
(author)
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Synergistically boosting performances of organic solar cells from dithieno[3,2-b]benzo[1,2-b;4,5-b′]dithiophene-based copolymers via side chain engineering and radical polymer additives
- 2024
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In: Journal of Materials Chemistry C. - 2050-7526 .- 2050-7534. ; 12:10, s. 3644-3653
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Journal article (peer-reviewed)abstract
- As a notable analogue of benzo[1,2-b:4,5-b′]dithiophene (BDT), dithieno[2,3-d:2′,3′-d′]benzo[1,2-b:4,5-b′]dithiophene (DTBDT) is expected to be a more promising building block for polymer photovoltaic donor materials due to its larger coplanar core and extended conjugation length as well as a similar electron donor ability to BDT. However, the performance of organic solar cells (OSCs) from DTBDT-based copolymers is much lower than that of OSCs from BDT-based copolymers, which is attributed to the higher voltage loss of the OSCs from DTBDT-based polymers as compared to that from BDT-based polymers. In this study, approaches such as increasing the donor (D) and acceptor (A) spacing by lengthening the side chains of the polymer donors and use of radical conjugated polymer additives are synergistically employed in OSCs from 2-alkyl-3-chlorothiophene flanked DTBDT-alt-1,3-bis(thiophen-2-yl)-5,7-bis(2-ethylhexyl)-4H,8H-benzo[1,2-c:4,5-c′]dithiophene-4,8-dione (BDD) polymers paired with Y6. Compared to the OSCs from the DTBDT-alt-BDD polymer with 2-ethylhexyl side chains (PBDT-Cl) paired with Y6, the power conversion efficiencies (PCEs) of the counterpart OSCs from the DTBDT-alt-BDD polymer with 2-butyloctyl side chains (PDBT-Cl-BO) increased from 12.67% to 14.58%, with a remarkable improvement of the open circuit voltage (VOC). The reduction of non-radiative energy loss of the OSCs from PBDT-Cl-BO:Y6, ascribed to the increase of the DA spacing by lengthening the side chains, is supported through detailed studies such as Fourier-transform photocurrent spectroscopy external quantum efficiency (FTPS-EQE), electroluminescence (EL), electroluminescence external quantum efficiency (EQEEL), and molecular dynamics simulations (MD). Afterwards, the PCEs of the OSCs from the blends of PDBT-Cl-BO:Y6 were further improved from 14.58% to 15.93% with a notable improvement of short circuit densities (JSCs) and fill factors (FFs), along with a small improvement in VOC upon the addition of the radical conjugated polymer GDTA as an additive. For comparison, the PCEs of the OSCs from the blends of PDBT-Cl:Y6 remained almost unchanged upon the addition of GDTA. This work suggests a wise strategy to synergistically utilize side-chain engineering and radical conjugated polymer additives to reduce the non-radiative energy loss, thus improving the performance of OSCs from DTBDT-based polymer donors.
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| 14. |
- Chen, Xin, 1980, et al.
(author)
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Dataset for suppressors of amyloid-beta toxicity and their functions in recombinant protein production in yeast
- 2022
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In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 42
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Journal article (peer-reviewed)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.
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| 15. |
- Chen, Xin, 1980, et al.
(author)
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Suppressors of amyloid-β toxicity improve recombinant protein production in yeast by reducing oxidative stress and tuning cellular metabolism
- 2022
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In: Metabolic Engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 72, s. 311-324
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Journal article (peer-reviewed)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.
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| 16. |
- Guan, Xiaowei, et al.
(author)
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Ultrasmall Directional Coupler and Disk-resonantor Based on Nano-scale Silicon Hybrid Plasmonic Waveguides
- 2012
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In: 2012 Asia Communications And Photonics Conference (ACP). - Washington, D.C. : OSA. - 9781467362740 ; , s. AS2H.4-
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Conference paper (peer-reviewed)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.
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| 17. |
- Guo, Huijie, et al.
(author)
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Regulation of photoinduced charge transfer in all-small-molecule organic solar cells through the synergistic effect of external electric field and solvent
- 2024
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In: Journal of Luminescence. - 0022-2313. ; 268
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Journal article (peer-reviewed)abstract
- The donor (BTR-Cl) and acceptor (BTP-FCl-FCl) have well-defined small molecule properties and excellent repeatability, and they can form charge transfer complexes with a wide spectral absorption range. Using density functional theory (DFT), we simulate the photoinduced charge transfer of bulk-heterojunction (BHJ) organic solar cell (OSC) materials modulated by the external electric field (Fext) at the microscopic level. The excited-state properties, reorganization energy (λ), Gibbs free energy (ΔG), electron coupling matrix elements (VDA) and intermolecular charge transfer (ICT) rate dependent on Fext are systematically analyzed. The results manifest that Fext has apparent positive regulation on the charge separation rate (KCS), and VDA is the main factor affecting KCS. The synergistic effect of solvent and Fext on charge transfer process is further investigated. It is found that the charge transfer rate in solvent is lower than that in solvent-free conditions, and the charge transfer rate in chlorobenzene (CB) solvent does not change significantly under the control of Fext. At the same time, Fext has a positive effect on the charge transfer rate in tetrahydrofuran (THF) solvent. Considering the charge transfer rate under different solvents and Fext intensities, it is found that the solvent and Fext play an essential role in determining the KCS and charge recombination rate (KCR).
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| 18. |
- Huang, Ke, et al.
(author)
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The confounding effect of snow cover on assessing spring phenology from space : A new look at trends on the Tibetan Plateau
- 2021
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In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 756
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Journal article (peer-reviewed)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.
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| 19. |
- Jha, Debesh, et al.
(author)
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A comprehensive analysis of classification methods in gastrointestinal endoscopy imaging
- 2021
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In: Medical Image Analysis. - 1361-8415 .- 1361-8423. ; 70
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Journal article (peer-reviewed)abstract
- Gastrointestinal (GI) endoscopy has been an active field of research motivated by the large number of highly lethal GI cancers. Early GI cancer precursors are often missed during the endoscopic surveillance. The high missed rate of such abnormalities during endoscopy is thus a critical bottleneck. Lack of attentiveness due to tiring procedures, and requirement of training are few contributing factors. An automatic GI disease classification system can help reduce such risks by flagging suspicious frames and lesions. GI endoscopy consists of several multi-organ surveillance, therefore, there is need to develop methods that can generalize to various endoscopic findings. In this realm, we present a comprehensive analysis of the Medico GI challenges: Medical Multimedia Task at MediaEval 2017, Medico Multimedia Task at MediaEval 2018, and BioMedia ACM MM Grand Challenge 2019. These challenges are initiative to set-up a benchmark for different computer vision methods applied to the multi-class endoscopic images and promote to build new approaches that could reliably be used in clinics. We report the performance of 21 participating teams over a period of three consecutive years and provide a detailed analysis of the methods used by the participants, highlighting the challenges and shortcomings of the current approaches and dissect their credibility for the use in clinical settings. Our analysis revealed that the participants achieved an improvement on maximum Mathew correlation coefficient (MCC) from 82.68% in 2017 to 93.98% in 2018 and 95.20% in 2019 challenges, and a significant increase in computational speed over consecutive years.
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| 20. |
- Li, Dongqing, et al.
(author)
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miR-19a/b and miR-20a promote wound healing by regulating the inflammatory response of keratinocytes
- 2021
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In: Journal of Investigative Dermatology. - : Elsevier. - 0022-202X .- 1523-1747. ; 141:3, s. 659-671
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Journal article (peer-reviewed)abstract
- Persistent and impaired inflammation impedes tissue healing and is characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. Here we show that in human wound-edge keratinocytes, the expression of miR-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, is upregulated during wound repair. However, their levels are lower in chronic ulcers than acute wounds at the proliferative phase. Conditional knockout of miR-17∼92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound-edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17∼92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines/cytokines by keratinocytes. Thus, as crucial regulators of wound inflammation, lack of miR-19a/b and miR-20a may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes.
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| 21. |
- Li, Xiaowei, 1986, et al.
(author)
-
Metabolic network remodelling enhances yeast’s fitness on xylose using aerobic glycolysis
- 2021
-
In: Nature Catalysis. - : Springer Science and Business Media LLC. - 2520-1158. ; 4:9, s. 783-796
-
Journal article (peer-reviewed)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.].
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| 22. |
- Lin, Yuze, et al.
(author)
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Balanced Partnership between Donor and Acceptor Components in Nonfullerene Organic Solar Cells with > 12% Efficiency
- 2018
-
In: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 30:16
-
Journal article (peer-reviewed)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.
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| 23. |
- Lin, Yuze, et al.
(author)
-
Mapping Polymer Donors toward High-Efficiency Fullerene Free Organic Solar Cells
- 2017
-
In: Advanced Materials. - : WILEY-V C H VERLAG GMBH. - 0935-9648 .- 1521-4095. ; 29:3
-
Journal article (peer-reviewed)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%.
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| 24. |
- Puram, Sidharth V., et al.
(author)
-
Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma
- 2023
-
In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:4, s. 640-650
-
Journal article (peer-reviewed)abstract
- Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.
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| 25. |
- Qiang, Mingrui, et al.
(author)
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Late Quaternary Dust, Loess and Desert Dynamics in Upwind Areas of the Chinese Loess Plateau
- 2021
-
In: Frontiers in Earth Science. - : Frontiers Media S.A.. - 2296-6463. ; 9
-
Journal article (peer-reviewed)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.
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| 26. |
- Shi, Xiaowei, et al.
(author)
-
The effect of ride experience on changing opinions toward autonomous vehicle safety
- 2021
-
In: Communications in Transportation Research. - : Elsevier BV. - 2772-4247. ; 1
-
Journal article (peer-reviewed)abstract
- Autonomous vehicles (AVs) are a promising emerging technology that is likely to be widely deployed in the near future. People's perception on AV safety is critical to the pace and success of deploying the AV technology. Existing studies found that people's perceptions on emerging technologies might change as additional information was provided. To investigate this phenomenon in the AV technology context, this paper conducted real-world AV experiments and collected factors that may associate with people's initial opinions without any AV riding experience and opinion change after a successful AV ride. A number of ordered probit and binary probit models considering data heterogeneity were employed to estimate the impact of these factors on people's initial opinions and opinion change. The study found that people's initial opinions toward AV safety are significantly associated with people's age, personal income, monthly fuel cost, education experience, and previous AV experience. Further, the factors dominating people's opinion change after a successful AV ride include people's age, personal income, monthly fuel cost, daily commute time, driving alone indicator, willingness to pay for AV technology, and previous AV experience. These results provide important references for future implementations of the AV technology. Additionally, based on the inconsistent effects for variables across different models, suggestions for future transportation survey designs are provided.
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| 27. |
- Tan, Yanhui, et al.
(author)
-
A marine fungus-derived nitrobenzoyl sesquiterpenoid suppresses receptor activator of NF-κB ligand-induced osteoclastogenesis and inflammatory bone destruction
- 2020
-
In: British Journal of Pharmacology. - : Wiley. - 0007-1188 .- 1476-5381. ; 177:18, s. 4242-4260
-
Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Osteoclasts are unique cells to absorb bone. Targeting osteoclast differentiation is a therapeutic strategy for osteolytic diseases. Natural marine products have already become important sources of new drugs. The naturally occurring nitrobenzoyl sesquiterpenoids first identified from marine fungi in 1998 are bioactive compounds with a special structure, but their pharmacological functions are largely unknown. Here, we investigated six marine fungus-derived nitrobenzoyl sesquiterpenoids on osteoclastogenesis and elucidated the mechanisms.EXPERIMENTAL APPROACH: Compounds were first tested by RANKL-induced NF-κB luciferase activity and osteoclastic TRAP assay, followed by molecular docking to characterize the structure-activity relationship. The effects and mechanisms of the most potent nitrobenzoyl sesquiterpenoid on RANKL-induced osteoclastogenesis and bone resorption were further evaluated in vitro. Micro-CT and histology analysis were used to assess the prevention of bone destruction by nitrobenzoyl sesquiterpenoids in vivo.KEY RESULTS: Nitrobenzoyl sesquiterpenoid 4, with a nitrobenzoyl moiety at C-14 and a hydroxyl group at C-9, was the most active compound on NF-κB activity and osteoclastogenesis. Consequently, nitrobenzoyl sesquiterpenoid 4 exhibited suppression of RANKL-induced osteoclastogenesis and bone resorption from 0.5 μM. It blocked RANKL-induced IκBa phosphorylation, NF-κB p65 and RelB nuclear translocation, NFATc1 activation, reduced DC-STAMP but not c-Fos expression during osteoclastogenesis in vitro. Nitrobenzoyl sesquiterpenoid 4 also ameliorated LPS-induced osteolysis in vivo.CONCLUSION AND IMPLICATIONS: These results highlighted nitrobenzoyl sesquiterpenoid 4 as a novel inhibitor of osteoclast differentiation. This marine-derived sesquiterpenoid is a promising lead compound for the treatment of osteolytic diseases.
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| 28. |
- Tian, Chen, et al.
(author)
-
Functional Failure Behavior of Submerged Entry Nozzle during the Continuous Casting Process of the Bearing Steel GCr15
- 2024
-
In: Steel Research International. - : John Wiley & Sons. - 1611-3683 .- 1869-344X.
-
Journal article (peer-reviewed)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.
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| 29. |
- Wang, Sailan, et al.
(author)
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Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans
- 2024
-
In: EMBO Molecular Medicine. - : EMBO Press. - 1757-4676 .- 1757-4684. ; 16:3, s. 596-615
-
Journal article (peer-reviewed)abstract
- Psoriatic arthritis mutilans (PAM) is the rarest and most severe form of psoriatic arthritis, characterized by erosions of the small joints and osteolysis leading to joint disruption. Despite its severity, the underlying mechanisms are unknown, and no susceptibility genes have hitherto been identified. We aimed to investigate the genetic basis of PAM by performing massive parallel sequencing in sixty-one patients from the PAM Nordic cohort. We found rare variants in the NADPH oxidase 4 (NOX4) in four patients. In silico predictions show that the identified variants are potentially damaging. NOXs are the only enzymes producing reactive oxygen species (ROS). NOX4 is specifically involved in the differentiation of osteoclasts, the cells implicated in bone resorption. Functional follow-up studies using cell culture, zebrafish models, and measurement of ROS in patients uncovered that these NOX4 variants increase ROS levels both in vitro and in vivo. We propose NOX4 as the first candidate susceptibility gene for PAM. Our study links high levels of ROS caused by NOX4 variants to the development of PAM, offering a potential therapeutic target.
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| 30. |
- Wang, Yanyan, 1989, et al.
(author)
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CRISPR/Cas9-mediated point mutations improve alpha-amylase secretion in Saccharomyces cerevisiae
- 2022
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In: FEMS Yeast Research. - : Oxford University Press (OUP). - 1567-1356 .- 1567-1364. ; 22:1
-
Journal article (peer-reviewed)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.
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| 31. |
- Wang, Yanyan, 1989, et al.
(author)
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Expression of antibody fragments in Saccharomyces cerevisiae strains evolved for enhanced protein secretion
- 2021
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In: Microbial Cell Factories. - : Springer Science and Business Media LLC. - 1475-2859. ; 20:1
-
Journal article (peer-reviewed)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.
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| 32. |
- Wang, Ziming, 1992, et al.
(author)
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Exploring Intended Functions of Indoor Flying Robots Interacting With Humans in Proximity
- 2024
-
In: Conference on Human Factors in Computing Systems - Proceedings.
-
Conference paper (peer-reviewed)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.
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| 33. |
- Yang, Zhijian, et al.
(author)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
-
In: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
-
Journal article (peer-reviewed)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.
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| 34. |
- Yu, Guimei, et al.
(author)
-
Structure of Arabidopsis SOQ1 lumenal region unveils C-terminal domain essential for negative regulation of photoprotective qH
- 2022
-
In: Nature Plants. - : Nature Publishing Group. - 2055-0278. ; 8:7, s. 840-855
-
Journal article (peer-reviewed)abstract
- Non-photochemical quenching (NPQ) plays an important role for phototrophs in decreasing photo-oxidative damage. qH is a sustained form of NPQ and depends on the plastid lipocalin (LCNP). A thylakoid membrane-anchored protein SUPPRESSOR OF QUENCHING1 (SOQ1) prevents qH formation by inhibiting LCNP. SOQ1 suppresses qH with its lumen-located thioredoxin (Trx)-like and NHL domains. Here we report structural data, genetic modification and biochemical characterization of Arabidopsis SOQ1 lumenal domains. Our results show that the Trx-like and NHL domains are associated together, with the cysteine motif located at their interface. Residue E859, required for SOQ1 function, is pivotal for maintaining the Trx–NHL association. Importantly, the C-terminal region of SOQ1 forms an independent β-stranded domain that has structural homology to the N-terminal domain of bacterial disulfide bond protein D and is essential for negative regulation of qH. Furthermore, SOQ1 is susceptible to cleavage at the loops connecting the neighbouring lumenal domains both in vitro and in vivo, which could be a regulatory process for its suppression function of qH.
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| 35. |
- Yu, Guimei, et al.
(author)
-
Structure of SOQ1 lumenal domains identifies potential disulfide exchange for negative regulation of photoprotection, qH
- 2024
-
Other publication (other academic/artistic)abstract
- Non-photochemical quenching (NPQ) plays an important role for phototrophs in decreasing photo-oxidative damage. qH is a sustained component of NPQ and depends on the plastid lipocalin (LCNP). A thylakoid membrane-anchored protein SUPPRESSOR OF QUENCHING1 (SOQ1) prevents qH formation by inhibiting LCNP. SOQ1 suppresses qH with its lumen-located C-terminal Trx-like and NHL domains. Here we report crystal structures and biochemical characterization of SOQ1 lumenal domains. Our results show that the Trx-like and NHL domains are stably associated, with the potential redox-active motif located at their interface. Residue E859 essential for SOQ1 function is pivotal for mediating the inter-domain interaction. Moreover, the C-terminal region of SOQ1 forms an independent β-stranded domain, which possibly interacts with the Trx-like domain through disulfide exchange. Furthermore, SOQ1 is susceptible to cleavage at the loops connecting the neighboring domains both in vitro and in vivo, which could be a regulatory process for its suppression function of qH.
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| 36. |
- Yu, Meijuan, et al.
(author)
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3D local structure around Zn in Kti11p as a representative Zn-(Cys)4 motif as obtained by MXAN
- 2008
-
In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 374:1, s. 28-32
-
Journal article (peer-reviewed)abstract
- Zinc is an important component of many proteins that play key roles in transcription, translation, and catalysis. Kti11p, DESR1, both belonging to a protein family characterized by a CSL zinc finger domain, and the co-catalytic zinc-protein PML containing a Zn2+ binding domain called RING or C3HC4 finger are all structurally determined by NMR although the zinc sites are silent to this spectroscopical method. The comparison of X-ray absorption near-edge spectroscopy (XANES) data for the three proteins demonstrates that fingerprints effect is a reliable method for a primary characterization of ligand species. Ab initio full MS Calculations performed by MAN are applied to obtain chemical and stereo structural information around the Zn ion in Kti11p. For the first time this high-spatial resolution technique confirms the formation of a stable Zn tetrahedral configuration with four sulfur ligands, and returns extremely accurate bond angle information between ligands.
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| 37. |
- Yuan, Jun, et al.
(author)
-
Reducing Voltage Losses in the A-DAD-A Acceptor-Based Organic Solar Cells
- 2020
-
In: Chem. - : CELL PRESS. - 2451-9308 .- 2451-9294. ; 6:9, s. 2147-2161
-
Journal article (peer-reviewed)abstract
- Power conversion efficiencies (PCEs) of solution-processed organic solar cells (OSCs) have recently reached 17.4% (certified) for single-junction devices. Crucial to this advancement is the development of non-fullerene acceptors (NFAs) since 2015. The recent A-DAD-A NFAs have attracted widespread attention because of their ladder-type electron-deficient-core-based central fused ring with improved transport properties and optimum energy levels. With the synergistic effect of electron-deficient-core and specific molecular geometry, the A-DADA molecules could achieve low voltage losses and high current generation at the same time, reaching new regimes of device physics and photophysics. This perspective will discuss the voltage losses in state-of-the-art A-DAD-A NFA-based OSCs and propose new molecular design strategies to achieve PCEs over 20% in OSCs based on these new acceptors by further decreasing their total voltage losses.
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| 38. |
- Zhang, Lin, et al.
(author)
-
Cr-promoted formation of B2+L21 composite nanoprecipitates and enhanced mechanical properties in ferritic alloy
- 2023
-
In: Acta Materialia. - : Elsevier. - 1359-6454 .- 1873-2453. ; 243
-
Journal article (peer-reviewed)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.
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| 39. |
- Zhang, Xiaobo, et al.
(author)
-
Effects of exercise and dietary interventions on serum metabolites in men with insomnia symptoms : A 6-month randomized controlled trial
- 2020
-
In: SPORTS MEDICINE AND HEALTH SCIENCE. - : Elsevier. - 2666-3376. ; 2:2, s. 95-101
-
Journal article (peer-reviewed)abstract
- Accumulating evidence show that exercise and diet interventions are associated with improved sleep quality. Studies investigating the effects of exercise and dieting on circulating metabolomics in people with sleep disorders, particularly insomnia, are scarce. This 6-month randomized study aimed to assess the effects of exercise and dietary interventions on serum metabolites in men with insomnia symptoms. Seventy-two Finnish men (age: 51.6 +/- 10.1 years) with chronic insomnia symptoms who were assigned to different intervention groups completed this study (exercise, n = 24; diet, n = 27; and control, n = 21). The Shapiro-Wilk W-test, Levene test, Spearman correlation analysis, and analysis of variance were used for data analysis. We found that exercise and diet intervention were associated with improved sleep quality and with a number of metabolites across different biochemical pathways. Although we could not show causality, our findings provide new insight into the biological mechanisms underlying the health effects of physical activity, diet, and sleep quality. Further investigation is needed to better understand the link among lifestyle, sleep quality, and metabolic health.
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| 40. |
- Zuo, Xiao, et al.
(author)
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Discharge state transition and cathode fall thickness evolution during chromium HiPIMS discharge
- 2017
-
In: Physics of Plasmas. - : AMER INST PHYSICS. - 1070-664X .- 1089-7674. ; 24:8
-
Journal article (peer-reviewed)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.
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