1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)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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3. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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4. |
- Meng, Yi, et al.
(author)
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2D and 3D Porphyrinic Covalent Organic Frameworks : The Influence of Dimensionality on Functionality
- 2020
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 59:9, s. 3624-3629
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Journal article (peer-reviewed)abstract
- The construction of 2D and 3D covalent organic frameworks (COFs) from functional moieties for desired properties has gained much attention. However, the influence of COFs dimensionality on their functionalities, which can further assist in COF design, has never been explored. Now, by selecting designed precursors and topology diagrams, 2D and 3D porphyrinic COFs (2D-PdPor-COF and 3D-PdPor-COF) are synthesized. By model building and Rietveld refinement of powder X-ray diffraction, 2D-PdPor-COF crystallizes as 2D sheets while 3D-PdPor-COF adopts a five-fold interpenetrated pts topology. Interestingly, compared with 2D-PdPor-COF, 3D-PdPor-COF showed interesting properties, including 1) higher CO2 adsorption capacity; 2) better photocatalytic performance; and 3) size-selective photocatalysis. Based on this study, we believe that with the incorporation of functional moieties, the dimensionality of COFs can definitely influence their functionalities.
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5. |
- Purnomo, Kartiko Arif, et al.
(author)
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Decoding Multiple Biofunctions of Maca on Its Anti-allergic, Anti-inflammatory, Anti-thrombotic, and Pro-angiogenic Activities
- 2021
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In: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 69:40, s. 11856-11866
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Journal article (peer-reviewed)abstract
- Four active partition layers and ten isolates, including (5R)- and (5S)-macapyrrolidone A (1a, 1b), and four new alkaloids, (5R)- and (5S)-macapyrrolidone B (2a, 2b) and macapyrrolins D, E (3, 4), were isolated from maca (Lepidium meyenii Walp.), an indigenous food plant from Peru. Derived from the n-hexane layer, the macamide-rich fraction exhibited pro-angiogenic activity on EPC and HUVEC cells. Anti-thrombotic activity was displayed by the polar part of maca extracts (n-butanol and water layers). Both 75% methanol aq. (midlower polar part) and n-hexane (low polar part) layers, which showed signs of fatty acid content, markedly inhibited superoxide and elastase release in an anti-inflammatory assay. The 75% methanol aq. layer showed strong anti-allergic activity, and macapyrrolin A (5) was found active based on beta-hexosaminidase release inhibition assays and a ChemGPS-NP experiment. These valuable bioactivity results suggest that maca is a food plant with good benefits for human health.
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6. |
- Tse, Yi-Kei, et al.
(author)
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Morphological and functional types of tricuspid regurgitation : prognostic value in patients undergoing tricuspid annuloplasty during left-sided valvular surgery
- 2023
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In: Clinical Research in Cardiology. - : Springer. - 1861-0684 .- 1861-0692. ; 112:10, s. 1463-1474
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Journal article (peer-reviewed)abstract
- Background The nonuniform benefit of tricuspid annuloplasty may be explained by the proportionality of tricuspid regurgitation (TR) severity to right ventricular (RV) area. The purpose of this study was to delineate distinct morphological phenotypes of functional TR and investigate their prognostic implications in patients undergoing tricuspid annuloplasty during left-sided valvular surgery. Methods The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area ( RVDA) were retrospectively assessed in 290 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from penalized splines and maximally selected rank statistics, patients were stratified into proportionate (EROA/RVDA ratio <= 1.74) and disproportionate TR (EROA/RVDA ratio > 1.74). Results Overall, 59 (20%) and 231 (80%) patients had proportionate and disproportionate TR, respectively. Compared to those with proportionate TR, patients with disproportionate TR were older, had a higher prevalence of atrial fibrillation, lower pulmonary pressures, more impaired RV function, and larger tricuspid leaflet tenting area. Over a median follow-up of 4.1 years, 79 adverse events (47 heart failure hospitalizations and 32 deaths) occurred. Patients with disproportionate TR had higher rates of adverse events than those with proportionate TR (32% vs 10%; P = 0.001) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based classification of TR severity in outcome prediction and provided incremental prognostic value to both the EuroSCORE II and STS score (incremental chi(2) = 6.757 and 9.094 respectively; both P < 0.05). Conclusions Disproportionate TR is strongly associated with adverse prognosis and may aid patient selection and risk stratification for tricuspid annuloplasty with left-sided valvular surgery.
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7. |
- Chen, Haoqian, et al.
(author)
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Towards renewable public transport : Mining the performance of electric buses using solar-radiation as an auxiliary power source
- 2022
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In: Applied Energy. - : ELSEVIER SCI LTD. - 0306-2619 .- 1872-9118. ; 325
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Journal article (peer-reviewed)abstract
- Transforming the road public transport to run on renewable energy is vital solution to achieve carbon neutral and net zero goals. This paper evaluates the potential of using solar radiation-generated electricity as an auxiliary power supplementary for the battery of electric buses, based on a developed framework that using publicly street-view panoramas, GPS trajectory data and DEM data as input parameters of solar radiation model. A case study of Qingdao, China with 547 bus routes, 28,661 street-view panoramas shows that the solar-radiation electricity generated at noon during the operation accounts for about one-fifth, one-eighth of the total elec-tricity consumption of a bus traveling one kilometer in a sunny day and a cloudy day, respectively. Spatial variability shows significant solar-radiation power generation advantages in newly-launched areas and expressway. The solar power generated in a sunny day can make a bus half of passengers and with air conditioner off at least one extra trip in 2:1 replacement schedule, and nearly close to one extra trip in 4:3 replacement schedule. A correlated relation between the solar-radiation power generation benefit and the operation schedule of electric buses is observed, implying that the high cost of 2:1 replacement schedule for long-distance routes during summer or winter can be reduced. The proposed framework can help us evaluate and understand the feasibility of solar radiation-generated electricity energy of electric bus fleets covering the large-scale urban areas at different times, locations, and weather conditions, so as to support effective decisions at better planning of PV-integrated electric buses.
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8. |
- Chen, Zhishan, et al.
(author)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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9. |
- Fernandez-Rozadilla, Ceres, et al.
(author)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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10. |
- Guo, Di, et al.
(author)
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Cholecystokinin-like peptide mediates satiety by inhibiting sugar attraction
- 2021
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 17:8
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Journal article (peer-reviewed)abstract
- Feeding is essential for animal survival and reproduction and is regulated by both internal states and external stimuli. However, little is known about how internal states influence the perception of external sensory cues that regulate feeding behavior. Here, we investigated the neuronal and molecular mechanisms behind nutritional state-mediated regulation of gustatory perception in control of feeding behavior in the brown planthopper and Drosophila. We found that feeding increases the expression of the cholecystokinin-like peptide, sulfakinin (SK), and the activity of a set of SK-expressing neurons. Starvation elevates the transcription of the sugar receptor Gr64f and SK negatively regulates the expression of Gr64f in both insects. Interestingly, we found that one of the two known SK receptors, CCKLR-17D3, is expressed by some of Gr64f-expressing neurons in the proboscis and proleg tarsi. Thus, we have identified SK as a neuropeptide signal in a neuronal circuitry that responds to food intake, and regulates feeding behavior by diminishing gustatory receptor gene expression and activity of sweet sensing GRNs. Our findings demonstrate one nutritional state-dependent pathway that modulates sweet perception and thereby feeding behavior, but our experiments cannot exclude further parallel pathways. Importantly, we show that the underlying mechanisms are conserved in the two distantly related insect species.
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