| 1. |
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| 2. |
- 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. |
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| 4. |
- Ablikim, M., et al.
(author)
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Improved measurements of X-cJ -> Sigma(+) (Sigma)over-bar(-) and Sigma(0)(Sigma)over-bar(0) decays
- 2018
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In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 97:5
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Journal article (peer-reviewed)abstract
- Using a data sample of (448.1 +/- 2.9) x 10(6) psi (3686) events collected with the BESIII detector at the BEPCII collider, we present measurements of branching fractions for the decays X-cJ -> Sigma(+) (Sigma) over bar (-) and Sigma(0) (Sigma) over bar (0) The decays X-c1.2 -> Sigma(+) (Sigma) over bar (-) and Sigma (Sigma) over bar (0) are observed for the first time, and the branching fractions for X-c0 -> Sigma(+) (Sigma) over bar (-) and Sigma(0) (Sigma) over bar (0) decays are measured with improved precision. The branching fraction ratios between the charged and neutral modes are consistent with the prediction of isospin symmetry.
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| 5. |
- Butler, Anne M., et al.
(author)
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Novel Loci Associated With PR Interval in a Genome-Wide Association Study of 10 African American Cohorts
- 2012
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In: Circulation: Cardiovascular Genetics. - 1942-325X. ; 5:6, s. 639-646
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Journal article (peer-reviewed)abstract
- Background-The PR interval, as measured by the resting, standard 12-lead ECG, reflects the duration of atrial/atrioventricular nodal depolarization. Substantial evidence exists for a genetic contribution to PR, including genome-wide association studies that have identified common genetic variants at 9 loci influencing PR in populations of European and Asian descent. However, few studies have examined loci associated with PR in African Americans. Methods and Results-We present results from the largest genome-wide association study to date of PR in 13 415 adults of African descent from 10 cohorts. We tested for association between PR (ms) and approximate to 2.8 million genotyped and imputed single-nucleotide polymorphisms. Imputation was performed using HapMap 2 YRI and CEU panels. Study-specific results, adjusted for global ancestry and clinical correlates of PR, were meta-analyzed using the inverse variance method. Variation in genome-wide test statistic distributions was noted within studies (lambda range: 0.9-1.1), although not after genomic control correction was applied to the overall meta-analysis (lambda: 1.008). In addition to generalizing previously reported associations with MEIS1, SCN5A, ARHGAP24, CAV1, and TBX5 to African American populations at the genome-wide significance level (P<5.0x10(-8)), we also identified a novel locus: ITGA9, located in a region previously implicated in SCN5A expression. The 3p21 region harboring SCN5A also contained 2 additional independent secondary signals influencing PR (P<5.0x10-8). Conclusions-This study demonstrates the ability to map novel loci in African Americans as well as the generalizability of loci associated with PR across populations of African, European, and Asian descent. (Circ Cardiovasc Genet. 2012;5:639-646.)
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| 6. |
- Byun, Jinyoung, et al.
(author)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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In: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
-
Journal article (peer-reviewed)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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| 7. |
- Cheng, Chao, et al.
(author)
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Mosaic chromosomal alterations are associated with increased lung cancer risk : insight from the INTEGRAL-ILCCO cohort analysis
- 2023
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In: Journal of Thoracic Oncology. - : Elsevier. - 1556-0864 .- 1556-1380.
-
Journal article (peer-reviewed)abstract
- Introduction: Mosaic chromosomal alterations (mCAs) detected in white blood cells represent a type of clonal hematopoiesis (CH) that is understudied compared with CH-related somatic mutations. A few recent studies indicated their potential link with nonhematological cancers, especially lung cancer. Methods: In this study, we investigated the association between mCAs and lung cancer using the high-density genotyping data from the OncoArray study of INTEGRAL-ILCCO, the largest single genetic study of lung cancer with 18,221 lung cancer cases and 14,825 cancer-free controls. Results: We identified a comprehensive list of autosomal mCAs, ChrX mCAs, and mosaic ChrY (mChrY) losses from these samples. Autosomal mCAs were detected in 4.3% of subjects, in addition to ChrX mCAs in 3.6% of females and mChrY losses in 9.6% of males. Multivariable logistic regression analysis indicated that the presence of autosomal mCAs in white blood cells was associated with an increased lung cancer risk after adjusting for key confounding factors, including age, sex, smoking status, and race. This association was mainly driven by a specific type of mCAs: copy-neutral loss of heterozygosity on autosomal chromosomes. The association between autosome copy-neutral loss of heterozygosity and increased risk of lung cancer was further confirmed in two major histologic subtypes, lung adenocarcinoma and squamous cell carcinoma. In addition, we observed a significant increase of ChrX mCAs and mChrY losses in smokers compared with nonsmokers and racial differences in certain types of mCA events. Conclusions: Our study established a link between mCAs in white blood cells and increased risk of lung cancer.
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| 8. |
- Ching, Tao-Chung, et al.
(author)
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The JCMT BISTRO-2 Survey: Magnetic Fields of the Massive DR21 Filament
- 2022
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In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 941:2
-
Journal article (peer-reviewed)abstract
- We present 850 mu m dust polarization observations of the massive DR21 filament from the B-fields In STar-forming Region Observations (BISTRO) survey, using the POL-2 polarimeter and the SCUBA-2 camera on the James Clerk Maxwell Telescope. We detect ordered magnetic fields perpendicular to the parsec-scale ridge of the DR21 main filament. In the subfilaments, the magnetic fields are mainly parallel to the filamentary structures and smoothly connect to the magnetic fields of the main filament. We compare the POL-2 and Planck dust polarization observations to study the magnetic field structures of the DR21 filament on 0.1-10 pc scales. The magnetic fields revealed in the Planck data are well-aligned with those of the POL-2 data, indicating a smooth variation of magnetic fields from large to small scales. The plane-of-sky magnetic field strengths derived from angular dispersion functions of dust polarization are 0.6-1.0 mG in the DR21 filament and similar to 0.1 mG in the surrounding ambient gas. The mass-to-flux ratios are found to be magnetically supercritical in the filament and slightly subcritical to nearly critical in the ambient gas. The alignment between column density structures and magnetic fields changes from random alignment in the low-density ambient gas probed by Planck to mostly perpendicular in the high-density main filament probed by James Clerk Maxwell Telescope. The magnetic field structures of the DR21 filament are in agreement with MHD simulations of a strongly magnetized medium, suggesting that magnetic fields play an important role in shaping the DR21 main filament and subfilaments.
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| 9. |
- Chou, Meng-Yun, et al.
(author)
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Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.
- 2009
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In: The Journal of clinical investigation. - 1558-8238. ; 119:5, s. 1335-49
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Journal article (peer-reviewed)abstract
- Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of oxidized lipoproteins and apoptotic cells. Adaptive immune responses to various oxidation-specific epitopes play an important role in atherogenesis. However, accumulating evidence suggests that these epitopes are also recognized by innate receptors, such as scavenger receptors on macrophages, and plasma proteins, such as C-reactive protein (CRP). Here, we provide multiple lines of evidence that oxidation-specific epitopes constitute a dominant, previously unrecognized target of natural Abs (NAbs) in both mice and humans. Using reconstituted mice expressing solely IgM NAbs, we have shown that approximately 30% of all NAbs bound to model oxidation-specific epitopes, as well as to atherosclerotic lesions and apoptotic cells. Because oxidative processes are ubiquitous, we hypothesized that these epitopes exert selective pressure to expand NAbs, which in turn play an important role in mediating homeostatic functions consequent to inflammation and cell death, as demonstrated by their ability to facilitate apoptotic cell clearance. These findings provide novel insights into the functions of NAbs in mediating host homeostasis and into their roles in health and diseases, such as chronic inflammatory diseases and atherosclerosis.
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| 10. |
- Feng, Yifan, et al.
(author)
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Fractal Superconducting Nanowire Single-Photon Detectors and Their Applications in Imaging
- 2022
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In: Proceedings of the 2022 Conference on Lasers and Electro-Optics Pacific Rim, CLEO/PR 2022. - : Optica Publishing Group.
-
Conference paper (peer-reviewed)abstract
- We present our research on fractal superconducting nanowire single-photon detectors and their applications in light detection and ranging (LiDAR), full-Stokes polarimetric imaging, and non-line-of-sight imaging.
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| 11. |
- Feng, Yifan, et al.
(author)
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Fractal Superconducting Nanowire Single-Photon Detectors and Their Applications in Imaging
- 2022
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In: 2022 Conference on Lasers and Electro-Optics Pacific Rim, CLEO-PR 2022 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc..
-
Conference paper (peer-reviewed)abstract
- We present our research on fractal superconducting nanowire single-photon detectors and their applications in light detection and ranging (LiDAR), full-Stokes polarimetric imaging, and non-line-of-sight imaging.
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| 12. |
- Fu, Xi, et al.
(author)
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Associations between environmental characteristics, high-resolution indoor microbiome, metabolome and allergic and non-allergic rhinitis symptoms for junior high school students
- 2023
-
In: Environmental Science. - : Royal Society of Chemistry. - 2050-7887 .- 2050-7895. ; 25:4, s. 791-804
-
Journal article (peer-reviewed)abstract
- Rhinitis is one of the most prevalent chronic diseases globally. Microbiome exposure affects the occurrence of rhinitis. However, previous studies did not differentiate allergic rhinitis (AR) and non-allergic rhinitis (NAR) in the microbial association analysis. In this study, we investigate 347 students in 8 junior high schools, Terengganu, Malaysia, who were categorized as healthy (70.9%), AR (13.8%) and NAR (15.3%) based on a self-administered questionnaire and skin prick tests of pollen, pet, mould and house dust mite allergens. Classroom microbial and metabolite exposure in vacuumed dust was characterized by PacBio long-read amplicon sequencing, quantitative PCR and LC-MS-based untargeted metabolomics. Our findings indicate a similar microbial association pattern between AR and NAR. The richness in Gammaproteobacteria was negatively associated with AR and NAR symptoms, whereas total fungal richness was positively associated with AR and NAR symptoms (p < 0.05). Brasilonema bromeliae and Aeromonas enteropelogenes were negatively associated with AR and NAR, and Deinococcus was positively associated with AR and NAR (p < 0.01). Pipecolic acid was protectively associated with AR and NAR symptoms (OR = 0.06 and 0.13, p = 0.009 and 0.045). A neural network analysis showed that B. bromeliae was co-occurring with pipecolic acid, suggesting that the protective role of this species may be mediated by releasing pipecolic acid. Indoor relative humidity and the weight of vacuum dust were associated with AR and NAR, respectively (p < 0.05), but the health effects were mediated by two protective bacterial species, Aliinostoc morphoplasticum and Ilumatobacter fluminis. Overall, our study reported a similar microbial association pattern between AR and NAR and also revealed the complex interactions between microbial species, environmental characteristics, and rhinitis symptoms.
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| 13. |
- Hao, Meng-Shu, et al.
(author)
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The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants Is Controlled by Cytosolic pH
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
-
Journal article (peer-reviewed)abstract
- NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K-0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O-2 and decylubiquinone as electron acceptors. The K-0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K-0.5(Ca2+) for NADPH oxidation was high (approximate to 100 mu M), yet 20-fold lower K-0.5(Ca2+) values were determined at pH 6.8. Lower K-0.5(Ca2+) values were observed with decylubiquinone than with O-2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene.
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| 14. |
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| 15. |
- Hao, Zifan, et al.
(author)
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High-performance eight-channel system with fractal superconducting nanowire single-photon detectors
- 2024
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In: Chip. - : Elsevier B.V.. - 2709-4723 .- 2772-2724. ; 3:2
-
Journal article (peer-reviewed)abstract
- Superconducting nanowire single-photon detectors (SNSPDs) have become a mainstream photon-counting technology that has been widely applied in various scenarios. So far, most multi-channel SNSPD systems, either reported in literature or commercially available, are polarization sensitive, that is, the system detection efficiency (SDE) of each channel is dependent on the state of polarization of the to-be-detected photons. Here, we reported an eight-channel system with fractal SNSPDs working in the wavelength range of 930 to 940 nm, which are all featured with low polarization sensitivity. In a close-cycled Gifford-McMahon cryocooler system with the base temperature of 2.2 K, we installed and compared the performance of two types of devices: (1) SNSPD, composed of a single, continuous nanowire and (2) superconducting nanowire avalanche photodetector (SNAP), composed of 16 cascaded units of two nanowires electrically connected in parallel. The highest SDE among the eight channels reaches 96−5+4%, with the polarization sensitivity of 1.02 and a dark-count rate of 13 counts per second. The average SDE for eight channels for all states of polarization is estimated to be 90 ± 5%. It is concluded that both the SNSPDs and the SNAPs can reach saturated, high SDE at the wavelength of interest, and the SNSPDs show lower dark-count (false-count) rates, whereas the SNAPs show better properties in the time domain. With the adoption of this system, we showcased the measurements of the second-order photon-correlation functions of light emission from a single-photon source based on a semiconductor quantum dot and from a pulsed laser. It is believed that this work will provide new choices of systems with single-photon detectors combining the merits of high SDE, low polarization sensitivity, and low noise that can be tailored for different applications.
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| 16. |
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| 17. |
- Hu, Nan, et al.
(author)
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Full-Stokes polarimetric measurements and imaging using a fractal superconducting nanowire single-photon detector
- 2022
-
In: Optica. - : Optica Publishing Group. - 2334-2536. ; 9:4, s. 346-351
-
Journal article (peer-reviewed)abstract
- Measuring the states of polarization (SoP) of light is fundamentally important for applications ranging from communication, sensing, spectroscopy, imaging, to navigation. Superconducting nanowire single-photon detectors (SNSPDs) are ideal detectors of choice for faint-light detection and measurements, but SNSPDs themselves cannot resolve the SoP of photons. Here, based on a fractal SNSPD, we demonstrate a full-Stokes polarimetric measurement system that can measure arbitrary SoP of faint light. The measured SoPs are in excellent agreement with those of a state-of-the-art commercial polarimeter, but the sensitivity of our system reaches -86.6 dBm, which is 26.6 dB better than that of the commercial counterpart. As a direct application, we further demonstrate remote polarimetric imaging (i.e., polarimetric LiDAR) with a complete set of polarimetric contrast.
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| 18. |
- Hu, Nan, et al.
(author)
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Photon-Counting LIDAR Based on a Fractal SNSPD
- 2021
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In: 2021 OPTICAL FIBER COMMUNICATIONS CONFERENCE AND EXPOSITION (OFC). - : IEEE.
-
Conference paper (peer-reviewed)abstract
- We report on a photon-counting LIDAR system based on a polarization-insensitive fractal SNSPD with high detection efficiency and high timing resolution, and showcase depth imaging of an object at 1560 nm with millimeter depth resolution.
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| 19. |
- Hu, Xiaolong, et al.
(author)
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Fractal superconducting nanowire single-photon detectors and their applications in polarimetric imaging
- 2024
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In: Advanced Photon Counting Techniques XVIII. - : SPIE-Intl Soc Optical Eng.
-
Conference paper (peer-reviewed)abstract
- In this paper, we review the research and development of the fractal superconducting nanowire single-photon detectors (SNSPDs), including our demonstrations of high-performance devices and systems with over 80% system detection efficiency, negligibly low residual polarization sensitivity, and low timing jitter. Using the fractal SNSPDs, we demonstrate full-Stokes polarimetric imaging LiDAR.
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| 20. |
- Hu, Xiaolong, et al.
(author)
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Superconducting nanowire single-photon detectors at the infrared spectrum range : detection efficiency and timing jitter
- 2019
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In: TERAHERTZ, RF, MILLIMETER, AND SUBMILLIMETER-WAVE TECHNOLOGY AND APPLICATIONS XII. - : SPIE. - 9781510624771
-
Conference paper (peer-reviewed)abstract
- This paper reviews some recent research progress in superconducting nanowire single-photon detectors (SNSPDs) at the infrared spectrum range, with particular emphasis on detection efficiency and timing jitter. For detection efficiency, we present fractal SNSPDs with reduced polarization sensitivity; for timing jitter, we present two mechanisms of device timing jitter - vortex-crossing-induced timing jitter and spatial-inhomogeneity-induced timing jitter.
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| 21. |
- Hu, Xiaolong, et al.
(author)
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Timing properties of superconducting nanowire single-photon detectors
- 2019
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In: Quantum Optics and Photon Counting 2019. - : SPIE - International Society for Optical Engineering. - 9781510627215
-
Conference paper (peer-reviewed)abstract
- In this paper, we review theoretical and experimental research progress on timing properties of superconducting nanowire single-photon detectors, including six possible mechanisms that induce timing jitter and experiments towards ultra-low timing jitter.
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| 22. |
- Huang, Zi-Nan, et al.
(author)
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Analysis of the stress field in the reactor vessel of the China Initiative Accelerator Driven System during postulated ULOF and UTOP transients
- 2023
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In: Annals of Nuclear Energy. - : Elsevier BV. - 0306-4549 .- 1873-2100. ; 194
-
Journal article (peer-reviewed)abstract
- The China Initiative Accelerator Driven System (CiADS) was proposed by China Academy of Science since 2015. The subcritical reactor in CiADS is a liquid Lead Bismuth Eutectic (LBE) cooled fast reactor. When the reactor core is in operation, the LBE coolant will directly contact and corrode the inner surface of reactor vessel. Due to the high temperature, the corrosion will be more severe. If the stress on the reactor vessel exceeds the limit, the plastic deformation will occur, leading to the generation and expansion of defects and cracks, and the safety of the reactor will be affected. Therefore, evaluating the stress field of the reactor vessel under different operating conditions is a very important research project. In this paper, the finite element analysis software ADINA was applied to analyze the reactor vessel in CiADS, and the ASME Code was used as stress assessment standards. We can preliminarily prove that the stress assessments of the vessel during the postulated Unprotected Loss of Flow (ULOF) accidents satisfy the requirements of ASME Code. The limit reactivity insertion to protect the vessel from plastic deformation is 0.58$ in the postulated Unprotected Transient over Power (UTOP) accidents based on our current results. Therefore, we can preliminarily conclude that the current material selection and structural design of the reactor vessel in CiADS could survive most of the postulated transient accidents considering the stress effect.
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| 23. |
- Karoly, Janik, et al.
(author)
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The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43
- 2023
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In: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 952:1
-
Journal article (peer-reviewed)abstract
- We present observations of polarized dust emission at 850 mu m from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (N-H2 similar to 10(22) - 10(23) cm(-2)) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to similar to 160 +/- 30 mu G in the main starless core and up to similar to 90 +/- 40 mu G in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvenic. We also present a new method of data reduction for these denser but fainter objects like starless cores.
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| 24. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)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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| 25. |
- Li, Yafang, et al.
(author)
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Lung cancer in ever- and never-smokers : findings from multi-population GWAS studies
- 2024
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association For Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 33:3, s. 389-399
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Clinical, molecular, and genetic epidemiology studies displayed remarkable differences between ever- and never-smoking lung cancer.METHODS: We conducted a stratified multi-population (European, East Asian, and African descent) association study on 44,823 ever-smokers and 20,074 never-smokers to identify novel variants that were missed in the non-stratified analysis. Functional analysis including expression quantitative trait loci (eQTL) colocalization and DNA damage assays, and annotation studies were conducted to evaluate the functional roles of the variants. We further evaluated the impact of smoking quantity on lung cancer risk for the variants associated with ever-smoking lung cancer.RESULTS: Five novel independent loci, GABRA4, intergenic region 12q24.33, LRRC4C, LINC01088, and LCNL1 were identified with the association at two or three populations (P < 5 × 10-8). Further functional analysis provided multiple lines of evidence suggesting the variants affect lung cancer risk through excessive DNA damage (GABRA4) or cis-regulation of gene expression (LCNL1). The risk of variants from 12 independent regions, including the well-known CHRNA5, associated with ever-smoking lung cancer was evaluated for never-smokers, light-smokers (packyear ≤ 20), and moderate-to-heavy-smokers (packyear > 20). Different risk patterns were observed for the variants among the different groups by smoking behavior.CONCLUSIONS: We identified novel variants associated with lung cancer in only ever- or never-smoking groups that were missed by prior main-effect association studies. IMPACT: Our study highlights the genetic heterogeneity between ever- and never-smoking lung cancer and provides etiologic insights into the complicated genetic architecture of this deadly cancer.
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