| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
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| 3. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 5. |
- Ravasi, Timothy, et al.
(författare)
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An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
- 2010
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Ingår i: CELL. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:5, s. 744-752
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Tidskriftsartikel (refereegranskat)abstract
- Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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| 6. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 7. |
- Brun, Matthias A, et al.
(författare)
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Semisynthesis of fluorescent metabolite sensors on cell surfaces.
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 133:40
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Tidskriftsartikel (refereegranskat)abstract
- Progress in understanding signal transduction and metabolic pathways is hampered by a shortage of suitable sensors for tracking metabolites, second messengers, and neurotransmitters in living cells. Here we introduce a class of rationally designed semisynthetic fluorescent sensor proteins, called Snifits, for measuring metabolite concentrations on the cell surface of mammalian cells. Functional Snifits are assembled on living cells through two selective chemical labeling reactions of a genetically encoded protein scaffold. Our best Snifit displayed fluorescence intensity ratio changes on living cells significantly higher than any previously reported cell-surface-targeted fluorescent sensor protein. This work establishes a generally applicable and rational strategy for the generation of cell-surface-targeted fluorescent sensor proteins for metabolites of interest.
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| 8. |
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| 9. |
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| 10. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 11. |
- Coughlin, Michael W., et al.
(författare)
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GROWTH on S190425z : Searching Thousands of Square Degrees to Identify an Optical or Infrared Counterpart to a Binary Neutron Star Merger with the Zwicky Transient Facility and Palomar Gattini-IR
- 2019
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 885:1
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Tidskriftsartikel (refereegranskat)abstract
- The third observing run by LVC has brought the discovery of many compact binary coalescences. Following the detection of the first binary neutron star merger in this run (LIGO/Virgo S190425z), we performed a dedicated follow-up campaign with the Zwicky Transient Facility (ZTF) and Palomar Gattini-IR telescopes. The initial skymap of this single-detector gravitational wave (GW) trigger spanned most of the sky observable from Palomar Observatory. Covering 8000 deg(2) of the initial skymap over the next two nights, corresponding to 46% integrated probability, ZTF system achieved a depth of 21 m(AB) in g- and r-bands. Palomar Gattini-IR covered 2200 square degrees in J-band to a depth of 15.5 mag, including 32% integrated probability based on the initial skymap. The revised skymap issued the following day reduced these numbers to 21% for the ZTF and 19% for Palomar Gattini-IR. We narrowed 338,646 ZTF transient ?alerts? over the first two nights of observations to 15 candidate counterparts. Two candidates, ZTF19aarykkb and ZTF19aarzaod, were particularly compelling given that their location, distance, and age were consistent with the GW event, and their early optical light curves were photometrically consistent with that of kilonovae. These two candidates were spectroscopically classified as young core-collapse supernovae. The remaining candidates were ruled out as supernovae. Palomar Gattini-IR did not identify any viable candidates with multiple detections only after merger time. We demonstrate that even with single-detector GW events localized to thousands of square degrees, systematic kilonova discovery is feasible.
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| 12. |
- Dang, Wen-Zhen, et al.
(författare)
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Therapeutic effects of artesunate on lupus-prone MRL/lpr mice are dependent on T follicular helper cell differentiation and activation of JAK2-STAT3 signaling pathway
- 2019
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Ingår i: Phytomedicine. - München : Elsevier. - 0944-7113 .- 1618-095X. ; 62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis. However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear.PURPOSE: The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/lpr mice and its regulatory function on Tfh cells.STUDY DESIGN AND METHODS: MRL/lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2-Stat3 signaling pathway.RESULTS: Upon oral administration, ART significantly prolonged the survival of MRL/lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment, T-cell compartment in the spleen of MRL/lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/lpr mice.CONCLUSION: ART showed therapeutic effects on lupus-prone MRL/lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2-Stat3 signaling cascade. Copyright © 2019 Elsevier GmbH
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| 13. |
- Engstrom, PG, et al.
(författare)
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Complex Loci in human and mouse genomes
- 2006
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 2:4, s. 564-577
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Fayle, Tom M, et al.
(författare)
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A positive relationship between ant biodiversity (Hymenoptera: Formicidae) and rate of scavenger-mediated nutrient redistribution along a disturbance gradient in a south-east Asian rain forest
- 2011
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Ingår i: MYRMECOLOGICAL NEWS. - : OESTERREICHISCHE GESELL ENTOMOFAUNISTIK, C/O NATURHISTOR MUSEUM WIEN, ZWEITE ZOOLOGISCHE ABTEILUNG (INSEKTEN), BURGRING 7, WIEN, AUSTRIA. - 1994-4136. ; 14, s. 5-12
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Tidskriftsartikel (refereegranskat)abstract
- Human modification of pristine habitats almost always leads to the local extinction of a subset of the species present. This means that the ecosystem processes carried out by the remaining species may change. It is well documented that particular species of ants carry out important ecosystem processes. However, while much work has been carried out to investigate the link between biodiversity and ecosystem functioning in other taxa, this has received relatively little attention for ant communities. In particular, no attempt has been made to link levels of ant diversity with the rates of nutrient redistribution carried out by scavenging species. Here we investigate the impacts of anthropogenic disturbance on the rate of scavenger-mediated nutrient redistribution, using bait-removal rate as a surrogate measure. We found that although ant species richness, diversity, biomass and rates of bait removal did not change systematically across the disturbance gradient, the rate of bait removal was related to ant species richness. Sites with more ant species experienced a faster rate of bait removal. This is the first documented positive relationship between ant species richness and the rate of an ecosystem process. If these results are applicable at larger spatial scales for a wider range of nutrient sources, loss of ant species could lead to important changes in the way that ecosystems function.
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| 15. |
- Frith, Martin C., et al.
(författare)
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Pseudo-messenger RNA : Phantoms of the transcriptome
- 2006
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 2:4, s. 504-514
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Tidskriftsartikel (refereegranskat)abstract
- The mammalian transcriptome harbours shadowy entities that resist classification and analysis. In analogy with pseudogenes, we define pseudo-messenger RNA to be RNA molecules that resemble protein- coding mRNA, but cannot encode full-length proteins owing to disruptions of the reading frame. Using a rigorous computational pipeline, which rules out sequencing errors, we identify 10,679 pseudo - messenger RNAs ( approximately half of which are transposonassociated) among the 102,801 FANTOM3 mouse cDNAs: just over 10% of the FANTOM3 transcriptome. These comprise not only transcribed pseudogenes, but also disrupted splice variants of otherwise protein- coding genes. Some may encode truncated proteins, only a minority of which appear subject to nonsense- mediated decay. The presence of an excess of transcripts whose only disruptions are opal stop codons suggests that there are more selenoproteins than currently estimated. We also describe compensatory frameshifts, where a segment of the gene has changed frame but remains translatable. In summary, we survey a large class of non- standard but potentially functional transcripts that are likely to encode genetic information and effect biological processes in novel ways. Many of these transcripts do not correspond cleanly to any identifiable object in the genome, implying fundamental limits to the goal of annotating all functional elements at the genome sequence level.
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| 16. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
-
Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 17. |
- Gao, Kai, et al.
(författare)
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Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring
- 2015
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Ingår i: Huanjing Kexue. - 0250-3301. ; 36:10, s. 3878-3883
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Tidskriftsartikel (refereegranskat)abstract
- CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments.
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| 18. |
- Gu, Shi-Ran, et al.
(författare)
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Phylogeny and re-circumscription of Cheniella (Leguminosae: Cercidoideae) based on plastome data and morphology, with description of three new species
- 2024
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Ingår i: TAXON. - 0040-0262 .- 1996-8175. ; 73:2, s. 475-502
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Tidskriftsartikel (refereegranskat)abstract
- Subfamily Cercidoideae is an early-diverging lineage of Leguminosae, within which the number and classification of genera have been controversial. Cheniella is a recently described genus in the Cercidoideae which requires revision and testing of its monophyly and circumscription. Here we infer the phylogenetic position and infrageneric relationships of Cheniella as well as the intergeneric relationships of Cercidoideae using 48 newly sequenced plastid genomes, including 34 individuals representing all species of Cheniella. Our phylogenetic analyses yield a well-resolved tree of Cercidoideae with robust support at most nodes. We also present morphological studies through field work and herbarium studies to re-assess the classification and circumscription of the genus. Based on the results of molecular analyses and morphological studies combined with distribution data, we broaden the circumscription of Cheniella to comprise a total of 15 species and 3 subspecies, including three new species (C. hechiensis, C. longistaminea, C. pubicarpa), one new combination (C. tianlinensis) and one new status and combination (C. longipes).
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| 19. |
- Hamdi, Yosr, et al.
(författare)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 20. |
- Hum, Yan Chai, et al.
(författare)
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A contrast enhancement framework under uncontrolled environments based on just noticeable difference
- 2022
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Ingår i: Signal processing. Image communication. - : Elsevier. - 0923-5965 .- 1879-2677. ; 103
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Tidskriftsartikel (refereegranskat)abstract
- Image contrast enhancement refers to an operation of remapping the pixels’ values of an image to emphasize desired information in the image. In this work, we propose a novel pixel-based (local) contrast enhancement algorithm, based on the human visual perception. First, we make an observation that pixels with lower regional contrast should be amplified for the purpose of enhancing the contrast and pixels with higher regional contrast should be suppressed to avoid undesired over-enhancement. To determine the quality of the regional contrast in the image (either lower or higher), a reference image will be created using a proposed global based contrast enhancement method (termed as Mean Brightness Bidirectional Histogram Equalization in the paper) for fast computation reason. To quantify the abovementioned regional contrast, we propose a method based on human visual perception taking Just Noticeable Difference (JND) into account. In short, our proposed algorithm is able to limit the enhancement of well-contrasted regions and enhance the poor contrast regions in an image. Both objective quality and subjective quality experimental results suggested that the proposed algorithm enhances images consistently across images with different dynamic range. We conclude that the proposed algorithm exhibits excellent consistency in producing satisfactory result for different type of images. It is important to note that the algorithm can be directly implemented in color space and not limited only to grayscale. The proposed algorithm can be obtained from the following GitHub link: https://github.com/UTARSL1/CHE.
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| 21. |
- Kang, Kai, et al.
(författare)
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Auction-based cloud service allocation and sharing for logistics product service system
- 2021
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Ingår i: Journal of Cleaner Production. - : Elsevier Ltd. - 0959-6526 .- 1879-1786. ; 278
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Tidskriftsartikel (refereegranskat)abstract
- Sustainability is increasingly viewed as a desired goal of social development. The logistics industry without exception is aware of the importance of sustainable development. To achieve this goal, the logistics industry is leveraging cutting-edge technologies, such as product service systems (PSS) and cloud manufacturing (CMfg), to design logistics product service systems (LPSS). In LPSS, public logistics resources are allocated to customers and private logistics resources are shared between customers. However, logistics resource allocation and sharing services have been impeded by a lack of efficient methods. In this context, this paper proposes an auction-based cloud service allocation and sharing method for LPSS. Firstly, LPSS is defined and elaborated based on the adoption of PSS in the logistics industry. Secondly, multi-unit Vickery (MV) auctions and one-sided Vickrey-Clarke-Groves (O-VCG) combinatorial auctions are proposed to address logistics resource allocation and sharing problems respectively in LPSS. Two auctions are introduced specifically, and their relevant properties are investigated, including incentive compatibility, allocative efficiency, budget balance, and individual rationality. Thirdly, computational studies are conducted to examine the performance of two auctions. The results reveal that MV auctions can efficiently allocate public logistics resources through ensuring the utility of logistics service providers under dynamic supply and demand. Additionally, O-VCG auctions can effectively integrate and share idle private logistics resources, which promotes sustainability in the logistics industry. Through integrating MV auctions with O-VCG auctions, the utility of logistics service providers can be increased.
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| 22. |
- Kuderna, Lukas F. K., et al.
(författare)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 23. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 24. |
- Liu, Zihe, et al.
(författare)
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Third-generation biorefineries as the means to produce fuels and chemicals from CO2
- 2020
-
Ingår i: Nature Catalysis. - : Springer Science and Business Media LLC. - 2520-1158. ; 3:3, s. 274-288
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Forskningsöversikt (refereegranskat)abstract
- Concerns regarding petroleum depletion and global climate change caused by greenhouse gas emissions have spurred interest in renewable alternatives to fossil fuels. Third-generation (3G) biorefineries aim to utilize microbial cell factories to convert renewable energies and atmospheric CO2 into fuels and chemicals, and hence represent a route for assessing fuels and chemicals in a carbon-neutral manner. However, to establish processes competitive with the petroleum industry, it is important to clarify/evaluate/identify the most promising CO2 fixation pathways, the most appropriate CO2 utilization models and the necessary productivity levels. Here, we discuss the latest advances in 3G biorefineries. Following an overview of applications of CO2 feedstocks, mainly from flue gas and waste gasification, we review prominent opportunities and barriers in CO2 fixation and energy capture. We then summarize reported CO2-based products and industries, and describe trends and key challenges for future advancement of 3G biorefineries. A shift from sugar-based feedstocks and biomass to the use of atmospheric CO2 for the bioproduction of fuels and chemicals is desirable. This Review describes how microorganisms can be engineered for CO2 fixation and industrial valorization of this key molecule.
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| 25. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
-
Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 26. |
- Murphy, Christine, et al.
(författare)
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Defying hard-to-heal wounds with an early antibiofilm intervention strategy : 'Wound hygiene'
- 2019
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Ingår i: Journal of Wound Care. - : Mark Allen Group. - 0969-0700 .- 2052-2916. ; 28:12, s. 818-822
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Tidskriftsartikel (refereegranskat)abstract
- Biofilm has been implicated as a barrier to wound healing and it is widely accepted that the majority of wounds not following a normal healing trajectory contain biofilm. Therefore, strategies that inform and engage clinicians to reduce biofilm and optimise the wound tissue environment to enable wound progression are of interest to wound care providers. In March 2019, an advisory board was convened where experts considered the barriers and opportunities to drive a broader adoption of a biofilm-based approach to wound care. Poor clarity and articulation of wound terminology were identified as likely barriers to clinical adoption of rigorous and proactive microbial decontamination that is supportive of wound healing advancement. A transition to an intuitive term such as 'wound hygiene' was proposed to communicate a comprehensive wound decontamination plan with an associated message of expected habitual routine. 'Wound hygiene', is a relatable concept that supports meticulous wound practice that addresses barriers to wound healing, such as biofilm, while aligning with antimicrobial stewardship programmes..
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| 27. |
- Ni, Xiangyin, et al.
(författare)
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Formation of forest gaps accelerates C, N and P release from foliar litter during 4 years of decomposition in an alpine forest
- 2018
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 139:3, s. 321-335
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Tidskriftsartikel (refereegranskat)abstract
- Relative to areas under canopy, the soils in forest gaps receive more irradiance and rainfall (snowfall); this change in microclimate induced by forest gaps may influence the release of carbon (C) and nutrients during litter decomposition. However, great uncertainty remains about the effects of forest gaps on litter decomposition. In this study, we incubated foliar litters from six tree and shrub species in forest gaps and canopy plots and measured the release of C, nitrogen (N) and phosphorus (P) in different snow cover periods in an alpine forest from 2012 to 2016. We found that N was retained by 24–46% but that P was immediately released during an early stage of decomposition. However, forest gaps decreased litter N retention, resulting in more N and P being released from decomposing litters for certain species (i.e., larch, birch and willow litters). Moreover, the release of C and nutrients during litter decomposition stimulated by forest gaps was primarily driven by warmer soil temperature in this high-altitude forest. We conclude that gap formation during forest regeneration may accelerate C turnover and nutrient cycling and that this stimulation might be regulated by the litter species in this seasonally snow-covered forest. © 2018, Springer Nature Switzerland AG.
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| 28. |
- Palacio, Montse, et al.
(författare)
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Prediction of neonatal respiratory morbidity by quantitative ultrasound lung texture analysis: a multicenter study.
- 2017
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 217:2
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Tidskriftsartikel (refereegranskat)abstract
- Prediction of neonatal respiratory morbidity may be useful to plan delivery in complicated pregnancies. The limited predictive performance of the current diagnostic tests together with the risks of an invasive procedure limits the use of fetal lung maturity assessment.The objective of the study was to evaluate the performance of quantitative ultrasound texture analysis (quantusFLM) to predict neonatal respiratory morbidity in preterm and early-term (<39.0 weeks) deliveries.This was a prospective multicenter study in 20 centers worldwide. Fetal lung ultrasound images were obtained at 25.0-38.6 weeks' gestation within 48 hours of delivery, stored in Digital Imaging and Communication in Medicine format, and analyzed with quantusFLM. Physicians were blinded to the analysis. At delivery, perinatal outcomes and the occurrence of neonatal respiratory morbidity, defined as either respiratory distress syndrome or transient tachypnea of the newborn, were registered. The performance of the ultrasound texture analysis test to predict neonatal respiratory morbidity was evaluated.A total of 883 images were collected, but 17.2% were discarded because of poor image quality or exclusion criteria, leaving 730 observations for the final analysis. The prevalence of neonatal respiratory morbidity was 13.8% (101 of 730). The quantusFLM predicted neonatal respiratory morbidity with a sensitivity, specificity, and positive and negative predictive value of 74.3% (75 of 101), 88.6% (557 of 629), 51.0% (75 of 147), and 95.5% (557 of 583), respectively. Accuracy was 86.5% (632 of 730) and positive and negative likelihood ratios were 6.5 and 0.3, respectively.The quantusFLM predicted neonatal respiratory morbidity with an accuracy similar to that previously reported for other tests with the advantage of being a noninvasive technique.
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| 29. |
- Pei, Xilong, et al.
(författare)
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RIS-Aided Wireless Communications : Prototyping, Adaptive Beamforming, and Indoor/Outdoor Field Trials
- 2021
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Ingår i: IEEE Transactions on Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0090-6778 .- 1558-0857. ; 69:12, s. 8627-8640
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Tidskriftsartikel (refereegranskat)abstract
- The prospects of using a Reconfigurable Intelligent Surface (RIS) to aid wireless communication systems have recently received much attention from academia and industry. Most papers make theoretical studies based on elementary models, while the prototyping of RIS-aided wireless communication and real-world field trials are scarce. In this paper, we describe a new RIS prototype consisting of 1100 controllable elements working at 5.8 GHz band. We propose an efficient algorithm for configuring the RIS over the air by exploiting the geometrical array properties and a practical receiver-RIS feedback link. In our indoor test, where the transmitter and receiver are separated by a 30 cm thick concrete wall, our RIS prototype provides a 26 dB power gain compared to the baseline case where the RIS is replaced by a copper plate. A 27 dB power gain was observed in the short-distance outdoor measurement. We also carried out long-distance measurements and successfully transmitted a 32 Mbps data stream over 500 m. A 1080p video was live-streamed and it only played smoothly when the RIS was utilized. The power consumption of the RIS is around 1 W. Our paper is vivid proof that the RIS is a very promising technology for future wireless communications.
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| 30. |
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| 31. |
- Sampson, Joshua N., et al.
(författare)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 32. |
- Schijven, Dick, et al.
(författare)
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Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
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Tidskriftsartikel (refereegranskat)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
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| 33. |
- Schrijver, Lieske H, et al.
(författare)
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Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers : an international cohort study
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 225:1, s. 1-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive preparations (OCPs) use. While the effects of OCPs in the general population are well established (∼50% reduction), the estimated risk reduction in mutation carriers is much less precise due to potential bias and small sample sizes. In addition, only a few studies have examined the associations between duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer.OBJECTIVE(S): To investigate in more detail the associations between various characteristics of OCP use and risk of ovarian cancer, to provide health care providers and carriers with better risk estimates.STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using OCP data on 3,989 BRCA1 and 2,445 BRCA2 mutation carriers. Age-dependent weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as covariate. To minimize survival bias, analyses were left-truncated at 5 years before baseline questionnaire. Separate analysis were conducted for each of the aspects of OCP use and in a multivariate analysis including all these aspects. In addition, the analysis of duration of OCP use was stratified by recency of use.RESULTS: OCPs were less often used by mutation carriers who were diagnosed with ovarian cancer (Ever use: BRCA1 58.6%, BRCA2 53.5%) than by unaffected carriers (Ever use: BRCA1 88.9%, BRCA2 80.7%. The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer, and 9 and 8 years for ovarian cancer unaffected BRCA1 and BRCA2 carriers, respectively. For BRCA1 mutation carriers univariate analyses showed that both a longer duration of OCP use and more recent use of OCPs were inversely associated with risk of ovarian cancer. However, in multivariate analyses including duration of use, age at first use and time since last use, duration of use proved to be the prominent protective factor (compared with <5 years, 5-9 years HR=0.67;95%CI 0.40-1.12, 10+ years HR=0.37;95%CI 0.19-0.73; ptrend=0.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (Duration of ≥10 years; BRCA1: <15 years since last use: HR=0.24 95%CI 0.14-0.43, 15+ years since last use: HR 0.56 95%CI 0.18-0.59). Univariate results for BRCA2 mutation carriers were similar, but due to limit sample size inconclusive.CONCLUSION: For BRCA1 mutation carriers, a longer duration of OCP use is associated with a greater reduction of ovarian cancer risk and the protection is long term.
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| 34. |
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| 35. |
- Voon, Wingates, et al.
(författare)
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Performance analysis of seven Convolutional Neural Networks (CNNs) with transfer learning for Invasive Ductal Carcinoma (IDC) grading in breast histopathological images
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Computer-aided Invasive Ductal Carcinoma (IDC) grading classification systems based on deep learning have shown that deep learning may achieve reliable accuracy in IDC grade classification using histopathology images. However, there is a dearth of comprehensive performance comparisons of Convolutional Neural Network (CNN) designs on IDC in the literature. As such, we would like to conduct a comparison analysis of the performance of seven selected CNN models: EfficientNetB0, EfficientNetV2B0, EfficientNetV2B0-21k, ResNetV1-50, ResNetV2-50, MobileNetV1, and MobileNetV2 with transfer learning. To implement each pre-trained CNN architecture, we deployed the corresponded feature vector available from the TensorFlowHub, integrating it with dropout and dense layers to form a complete CNN model. Our findings indicated that the EfficientNetV2B0-21k (0.72B Floating-Point Operations and 7.1 M parameters) outperformed other CNN models in the IDC grading task. Nevertheless, we discovered that practically all selected CNN models perform well in the IDC grading task, with an average balanced accuracy of 0.936 ± 0.0189 on the cross-validation set and 0.9308 ± 0.0211on the test set.
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| 36. |
- Wang, Kai, et al.
(författare)
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A one-carbon chemicals conversion strategy to produce precursor of biofuels with Saccharomyces cerevisiae
- 2023
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Ingår i: Renewable Energy. - : Elsevier BV. - 0960-1481 .- 1879-0682. ; 208, s. 331-340
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Tidskriftsartikel (refereegranskat)abstract
- Utilization of one-carbon chemicals such as CO2, formate, and methanol by microorganisms can enable the sustainable production of fuels and chemicals. However, the low conversion efficiency of these chemicals by microorganisms is a major challenge. To address this, we designed a one-carbon strategy that can utilize CO2 and its derivative formate. Here, a platform yeast strain with improved formate utilization and NAD(P)H production was constructed and evaluated for its ability to produce free fatty acids (FFAs). Based on 13C-marked analysis, the one-carbon assimilation efficiency of the platform strain reached 11.24%. Through continuous optimization, under conditions of glucose feeding the formate utilization rate of the final strain reached 0.48 g/L/h, with the final titer of FFAs reached 10.1 g/L, which represented improvements of 21.8 times and 33.7 times, respectively. As such, the produced FFAs can be easily transformed into biodiesel by combining them with downstream technologies in future research.
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| 37. |
- Wang, Kai, et al.
(författare)
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The transition from 2G to 3G-feedstocks enabled efficient production of fuels and chemicals
- 2023
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Ingår i: Green Energy and Environment. - 2468-0257 .- 2096-2797. ; In Press
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Tidskriftsartikel (refereegranskat)abstract
- For decades micoorganisms have been engineered for the utilization of lignocellulose-based second-generation (2G) feedstocks, but with the concerns of increased levels of atmospheric CO2 causing global warming there is an emergent need to transition from the utilization of 2G feedstocks to third-generation (3G) feedstocks such as CO2 and its derivatives. Here, we established a yeast platform that is capable of simultaneously converting 2G and 3G feedstocks into bulk and value-added chemicals. We demonstrated that by adopting 3G substrates such as CO2 and formate, the conversion of 2G feedstocks could be substantially improved. Specifically, formate could provide reducing power and energy for xylose conversion into valuable chemicals. Simultaneously, it can form a concentrated CO2 pool inside the cell, providing thermodynamically and kinetically favoured amounts of precursors for CO2 fixation pathways, e.g. the Calvin–Benson–Bassham (CBB) cycle. Furthermore, we demonstrated that formate could directly be utilized as a carbon source by yeast to synthesize endogenous amino acids. The engineered strain achieved a one-carbon (C1) assimilation efficiency of 9.2 %, which was the highest efficiency observed in the co-utilization of 2G and 3G feedstocks. We applied this strategy for productions of both bulk and value-added chemicals, including ethanol, free fatty acids (FFAs), and longifolene, resulting in yield enhancements of 18.4 %, 49.0 %, and ∼100 %, respectively. The strategy demonstrated here for co-utilization of 2G and 3G feedstocks sheds lights on both basic and applied research for the up-coming establishment of 3G biorefineries.
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| 38. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 39. |
- Williamson, Alice, et al.
(författare)
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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:6, s. 973-983
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Tidskriftsartikel (refereegranskat)abstract
- Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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| 40. |
- Zhao, Yan, et al.
(författare)
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Objective sleep characteristics and continuous glucose monitoring profiles of type 2 diabetes patients in real-life settings
- 2023
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 25:3, s. 823-831
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Given the significant role of sleep in glycemic control, the association between sleep and glycemic variability determined by continuous glucose monitoring (CGM) is worth investigating among patients with type 2 diabetes (T2D).METHODS: CGM was carried out among 28 T2D patients (aged 62.3±4.8 years, 57% women). Sleep characteristics were assessed by actigraphy within the CGM period. CGM-derived outcomes included glucose level, percentages of time in range (TIR) and time above range (TAR) during the monitoring period. Associations between intraindividual night-to-night variations of sleep characteristics and overall CGM outcomes were analyzed by linear regression. Associations between sleep characteristics in each night and time-matched CGM outcomes were analyzed by linear mixed models.RESULTS: A total 249 person-days of CGM coupled with 221 nights of sleep characteristics were documented. Greater standard deviation (SD) of objective sleep duration (minutes) between measurement nights was associated with higher glucose level (mmol/L, Coefficient [95% CI]: 0.018 [0.004, 0.033], P=0.017), smaller proportion of TIR (% in observation period, -0.20 [-0.36, -0.03], P=0.023), and greater proportion of TAR (0.22 [0.06, 0.39], P=0.011). Later sleep midpoint (minutes from 00:00) was associated with greater SD of glucose during the same sleep period (0.002 [0.0001, 0.003], P=0.037), longer nocturnal sleep duration was associated with smaller coefficient of variance of glucose level in the upcoming day (%, -0.015 [-0.03, -0.001], P=0.041).CONCLUSION: Objectively-determined sleep duration and sleep midpoint, as well as their daily variability, are associated with CGM-derived glucose profiles in T2D patients.
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