| 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. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)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. |
- Lu, R.S., et al.
(författare)
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A ring-like accretion structure in M87 connecting its black hole and jet
- 2023
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Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
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Tidskriftsartikel (refereegranskat)abstract
- The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
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| 5. |
- Nie, Huizhen, et al.
(författare)
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The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
- 2021
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
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Tidskriftsartikel (refereegranskat)abstract
- Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
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| 6. |
- Wu, Zi Yi, et al.
(författare)
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Convective transport characteristics of condensing droplets in moist air flow
- 2023
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Ingår i: Physics of Fluids. - : AIP Publishing. - 1070-6631 .- 1089-7666. ; 35:2
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Tidskriftsartikel (refereegranskat)abstract
- Condensation of convective moist air flow is a crucial physical process and is directly related to various industries. It is essential to understand the underlying growth mechanism of condensing droplets, while past studies have commonly considered convective transport with a negligible/simplified approach. In this work, a three-dimensional transient multiphysics coupling model was developed to investigate the transport characteristics of condensing droplets in convective moist air flow. This model typically interconnects heat transfer with vapor-liquid phase change, mass transport, and fluid flow. The results reveal that convective flow significantly dominates heat and mass transport during condensation. On the gas side, the incoming flow thins the diffusion layer at the windward part with a large concentration gradient. However, a low vapor-concentration zone behind the droplet is formed due to the resulting rear-side vortex, which presents an increased influence as the contact angle increases. By forcing molecular diffusion with convection transport, vapor transport from surroundings to the condensing interface is enhanced several times depending on the Reynolds number. Within the droplet, the flow shearing at the interface is principally responsible for the strong internal convection, while the Marangoni effect is negligible. The internal flow greatly affects the droplet temperature profile with a large gradient close to the base. Finally, convective flow contributes to over 3.3 times higher overall heat transfer coefficient than the quiescent environment. In addition, in interaction-governed growth, transport characteristics depend on not only the size and space distributions of droplets but also the interaction between droplets and convective flow.
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| 7. |
- Zheng, Shao Fei, et al.
(författare)
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Theoretical and Three-Dimensional Molecular Dynamics Study of Droplet Wettability and Mobility on Lubricant-Infused Porous Surfaces
- 2023
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Ingår i: Langmuir. - 0743-7463. ; 39:37, s. 13371-13385
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Tidskriftsartikel (refereegranskat)abstract
- Profiting from their slippery nature, lubricant-infused porous surfaces endow with droplets excellent mobility and consequently promise remarkable heat transfer improvement for dropwise condensation. To be a four-phase wetting system, the droplet wettability configurations and the corresponding dynamic characteristics on lubricant-infused porous surfaces are closely related to many factors, such as multiple interfacial interactions, surface features, and lubricant thickness, which keeps a long-standing challenge to promulgate the underlying physics. In this work, thermodynamically theoretical analysis and three-dimensional molecular dynamics simulations with the coarse-grained water and hexane models are carried out to explore droplet wettability and mobility on lubricant-infused porous surfaces. Combined with accessible theoretical criteria, phase diagrams of droplet configurations are constructed with a comprehensive consideration of interfacial interactions, surface structures, and lubricant thickness. Subsequently, droplet sliding and coalescence dynamics are quantitatively defined under different configurations. Finally, in terms of the promotion of dropwise condensation, a non-cloaking configuration with the encapsulated state underneath the droplet is recommended to achieve high droplet mobility owing to the low viscous drag of the lubricant and the eliminated pinning effect of the contact line. On the basis of the low oil-water and water-solid interactions, a stable lubricant layer with a relatively low thickness is suggested to construct slippery surfaces.
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| 8. |
- Chang, Rene Wei-Jung, et al.
(författare)
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Precision Science on Incidence and Progression of Early-Detected Small Breast Invasive Cancers by Mammographic Features
- 2020
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977-1985 and 1996-2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50-5.26)) and stellate masses (3.76, (95% CI, 3.15-4.53)) but shorter for circular masses (2.65, (95% CI, 2.06-3.55)) in 1996-2010. The similar trends, albeit longer MSTs, were also noted in 1977-1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.
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| 9. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 10. |
- 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
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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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