| 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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| 2. |
- Forsman, Lina Davies, et al.
(author)
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Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China : a study protocol of a prospective observational cohort study
- 2018
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In: BMJ Open. - : BMJ. - 2044-6055. ; 8:9
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Journal article (peer-reviewed)abstract
- Individualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB.Methods and analysis: Adult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960.Ethics and dissemination: This study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal. Trial registration number NCT02816931; Pre-results.
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| 3. |
- Hsu, Fang-Chi, et al.
(author)
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A novel prostate cancer susceptibility locus at 19q13.
- 2009
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In: Cancer research. - 1538-7445. ; 69:7, s. 2720-3
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Journal article (peer-reviewed)abstract
- A two-stage genome-wide association study (GWAS) of the Cancer Genetic Markers of Susceptibility (CGEMS) initiative identified single nucleotide polymorphisms (SNP) in 150 regions across the genome that may be associated with prostate cancer (PCa) risk. We filtered these results to identify 43 independent SNPs where the frequency of the risk allele was consistently higher in cases than in controls in each of the five CGEMS study populations. Genotype information for 22 of these 43 SNPs was obtained either directly by genotyping or indirectly by imputation in our PCa GWAS of 500 cases and 500 controls selected from a population-based case-control study in Sweden [Cancer of the Prostate in Sweden (CAPS)]. Two of these 22 SNPs were significantly associated with PCa risk (P<0.05). We then genotyped these two SNPs in the remaining cases (n=2,393) and controls (n=1,222) from CAPS and found that rs887391 at 19q13 was highly associated with PCa risk (P=9.4 x 10(-4)). A similar trend of association was found for this SNP in a case-control study from Johns Hopkins Hospital (JHH), albeit the result was not statistically significant. Altogether, the frequency of the risk allele of rs887391 was consistently higher in cases than controls among each of seven study populations examined, with an overall P=3.2 x 10(-7) from a combined allelic test. A fine-mapping study in a 110-kb region at 19q13 among CAPS and JHH study populations revealed that rs887391 was the most strongly associated SNP in the region. Additional confirmation studies of this region are warranted.
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| 4. |
- Zheng, Xubin, et al.
(author)
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Development and validation of a simple LC-MS/MS method for simultaneous determination of moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol in human plasma
- 2020
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In: Journal of chromatography. B. - : ELSEVIER. - 1570-0232 .- 1873-376X. ; 1158
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Journal article (peer-reviewed)abstract
- Treatment of multidrug-resistant tuberculosis (MDR-TB) is challenging due to high treatment failure rate and adverse drug events. This study aimed to develop and validate a simple LC-MS/MS method for simultaneous measurement of five TB drugs in human plasma and to facilitate therapeutic drug monitoring (TDM) in MDR-TB treatment to increase efficacy and reduce toxicity. Moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol were prepared in blank plasma from healthy volunteers and extracted using protein precipitation reagent containing trichloroacetic acid. Separation was achieved on an Atlantis T3 column with gradient of 0.1% formic acid in water and acetonitrile. Drug concentrations were determined by dynamic multiple reaction monitoring in positive ion mode on a LC-MS/MS system. The method was validated according to the United States Food and Drug Administration (FDA) guideline for bioanalytical method validation. The calibration curves for moxifloxacin, levofloxacin, prothionamide, pyrazinamide and ethambutol were linear, with the correlation coefficient values above 0.993, over a range of 0.1-5, 0.4-40, 0.2-10, 2-100 and 0.2-10 mg/L, respectively. Validation showed the method to be accurate and precise with bias from 6.5% to 18.3% for lower limit of quantification and -5.8% to 14.6% for LOW, medium (MED) and HIGH drug levels, and with coefficient of variations within 11.4% for all levels. Regarding dilution integrity, the bias was within 7.2% and the coefficient of variation was within 14.9%. Matrix effect (95.7%-112.5%) and recovery (91.4%-109.7%) for all drugs could be well compensated by their isotope-labelled internal standards. A benchtop stability test showed that the degradation of prothionamide was over 15% after placement at room temperature for 72 h. Clinical samples (n = 224) from a cohort study were analyzed and all concentrations were within the analytical range. The signal of prothionamide was suppressed in samples with hemolysis which was solved by sample dilution. As the method is robust and sample preparation is simple, it can easily be implemented to facilitate TDM in programmatic MDR-TB treatment.
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| 5. |
- Ainsworth, Richard I, et al.
(author)
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Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function.
- 2022
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted activepathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
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| 6. |
- Chen, Ping, et al.
(author)
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The First Data Release of CNIa0.02-A Complete Nearby (Redshift <0.02) Sample of Type Ia Supernova Light Curves
- 2022
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 259:2
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Journal article (peer-reviewed)abstract
- The CNIa0.02 project aims to collect a complete, nearby sample of Type Ia supernovae (SNe Ia) light curves, and the SNe are volume-limited with host-galaxy redshifts zhost < 0.02. The main scientific goal is to infer the distributions of key properties (e.g., the luminosity function) of local SNe Ia in a complete and unbiased fashion in order to study SN explosion physics. We spectroscopically classify any SN candidate detected by the All-Sky Automated Survey for Supernovae (ASAS-SN) that reaches a peak brightness <16.5 mag. Since ASAS-SN scans the full sky and does not target specific galaxies, our target selection is effectively unbiased by host-galaxy properties. We perform multiband photometric observations starting from the time of discovery. In the first data release (DR1), we present the optical light curves obtained for 247 SNe from our project (including 148 SNe in the complete sample), and we derive parameters such as the peak fluxes, Δm15, and sBV.
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| 7. |
- Chen, Zhipeng, et al.
(author)
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Design, Synthesis, and Structure-Activity Relationship of N-Aryl-N'-(thiophen-2-yl) thiourea Derivatives as Novel and Specific Human TLR1/2 Agonists for Potential Cancer Immunotherapy
- 2021
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In: Journal of Medicinal Chemistry. - Washington, DC : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 64:11, s. 7371-7389
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Journal article (peer-reviewed)abstract
- The previous virtual screening of ten million compounds yielded two novel nonlipopeptide-like chemotypes as TLR2 agonists. Herein, we present the chemical optimization of our initial hit, 1-phenyl-3-(thiophen-2-yl) urea, which resulted in the identification of SMU-C80 (EC50 = 31.02 ± 1.01 nM) as a TLR2-specific agonist with a 370-fold improvement in bioactivity. Mechanistic studies revealed that SMU-C80, through TLR1/2, recruits the adaptor protein MyD88 and triggers the NF-κB pathway to release cytokines such as TNF-α and IL-1β from human, but not murine, cells. To the best of our knowledge, it is the first species-specific TLR1/2 agonist reported until now. Moreover, SMU-C80 increased the percentage of T, B, and NK cells ex vivo and activated the immune cells, which suppressed cancer cell growth in vitro. In summary, we obtained a highly efficient and specific human TLR1/2 agonist that acts through the MyD88 and NF-κB pathway, facilitating cytokine release and the simultaneous activation of immune cells that in turn affects the apoptosis of cancer cells. © 2021 American Chemical Society
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| 8. |
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| 9. |
- Li, Yi, et al.
(author)
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Promoting photocatalytic hydrogen evolution by modulating the electron-transfer in an ultrafast timescale through Mo-S6 configuration
- 2024
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In: Journal of Materials Science and Technology. - 1005-0302. ; 193, s. 73-80
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Journal article (peer-reviewed)abstract
- Maximizing ultrafast electron-transfer kinetics in semiconductor is pivotal but challenging for high-efficiency solar-to-energy during the photocatalytic reaction process due to the intrinsic property of photocatalysts with low surface electron density. Herein, a model photocatalyst CdS@Mo is synthesized through a typical hydrothermal method for modulating the ultrafast electron-transfer to enhance the surface electron density. X-ray absorption fine spectra (XAFS) reveal that Mo is coordinated with S atoms to form a Mo-S6 configuration which is different from common MoS2 and Mo foil structures. Based on the femtosecond transient absorption spectra (fs-TAS), it is found that the formation of Mo-S6 configuration contributes to the fast decay of CdS signal and Mo-S6 signal reactivation, illustrating the ultrafast electron-transfer (∼2.2 ps) from CdS to Mo-S6 configuration, which achieves the enhanced electron density of photocatalyst surface. Finally, a holistic photocatalytic performance evaluation discloses that the growing of Mo-S6 configuration obviously improves the photocatalytic hydrogen evolution (PHE) efficiency of CdS from 28.5 to 47.5 mmol g–1 h–1 with a solar-to-hydrogen (STH) efficiency of 0.10 % which is seldomly discussed in the system containing sacrificial agents. This work opens a new path to modulate the surface electron density by tuning the ultrafast electron-transfer for enhancing reaction efficiency in electron-density-dependent systems.
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| 10. |
- ODonnell, Michael, et al.
(author)
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Registered Replication Report: Dijksterhuis and van Knippenberg (1998)
- 2018
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In: Perspectives on Psychological Science. - : SAGE PUBLICATIONS LTD. - 1745-6916 .- 1745-6924. ; 13:2, s. 268-294
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Journal article (peer-reviewed)abstract
- Dijksterhuis and van Knippenberg (1998) reported that participants primed with a category associated with intelligence (professor) subsequently performed 13% better on a trivia test than participants primed with a category associated with a lack of intelligence (soccer hooligans). In two unpublished replications of this study designed to verify the appropriate testing procedures, Dijksterhuis, van Knippenberg, and Holland observed a smaller difference between conditions (2%-3%) as well as a gender difference: Men showed the effect (9.3% and 7.6%), but women did not (0.3% and -0.3%). The procedure used in those replications served as the basis for this multilab Registered Replication Report. A total of 40 laboratories collected data for this project, and 23 of these laboratories met all inclusion criteria. Here we report the meta-analytic results for those 23 direct replications (total N = 4,493), which tested whether performance on a 30-item general-knowledge trivia task differed between these two priming conditions (results of supplementary analyses of the data from all 40 labs, N = 6,454, are also reported). We observed no overall difference in trivia performance between participants primed with the professor category and those primed with the hooligan category (0.14%) and no moderation by gender.
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