| 1. |
- Tran, Ngoc Hieu, et al.
(författare)
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Genetic profiling of Vietnamese population from large-scale genomic analysis of non-invasive prenatal testing data
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The under-representation of several ethnic groups in existing genetic databases and studies have undermined our understanding of the genetic variations and associated traits or diseases in many populations. Cost and technology limitations remain the challenges in performing large-scale genome sequencing projects in many developing countries, including Vietnam. As one of the most rapidly adopted genetic tests, non-invasive prenatal testing (NIPT) data offers an alternative untapped resource for genetic studies. Here we performed a large-scale genomic analysis of 2683 pregnant Vietnamese women using their NIPT data and identified a comprehensive set of 8,054,515 single-nucleotide polymorphisms, among which 8.2% were new to the Vietnamese population. Our study also revealed 24,487 disease-associated genetic variants and their allele frequency distribution, especially 5 pathogenic variants for prevalent genetic disorders in Vietnam. We also observed major discrepancies in the allele frequency distribution of disease-associated genetic variants between the Vietnamese and other populations, thus highlighting a need for genome-wide association studies dedicated to the Vietnamese population. The resulted database of Vietnamese genetic variants, their allele frequency distribution, and their associated diseases presents a valuable resource for future genetic studies.
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| 2. |
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| 3. |
- Dofs, Erik, et al.
(författare)
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The equation x(1)/x(2) + x(2)/x(3) + x(3)/x(4) + x(4)/x(1) = n
- 2022
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Ingår i: International Journal of Number Theory. - : World Scientific Pub Co Pte Ltd. - 1793-0421. ; 18:01, s. 75-87
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Tidskriftsartikel (refereegranskat)abstract
- It is a subtle question as to when the Diophantine equation of the tittle has solutions in positive integers. Here, we show that the equation in the title does not have solutions in positive integers in the case that n is of the form n = 4q, where q(2) - 1 = 2(h)q(1), with h, q(1) is an element of Z(+), 2 vertical bar h, h >= 4, and 8 vertical bar q(1) + 1. We do this by explicitly calculating a Brauer-Manin obstruction to weak approximation on the elliptic surface defined by the title equation.
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| 4. |
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| 5. |
- Nguyen, Hanh H., et al.
(författare)
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AFFnet - a deep convolutional neural network for the detection of atypical femur fractures from anteriorposterior radiographs
- 2024
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Ingår i: Bone. - 8756-3282 .- 1873-2763. ; , s. 117215-117215
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Tidskriftsartikel (refereegranskat)abstract
- Despite well-defined criteria for radiographic diagnosis of atypical femur fractures (AFFs), missed and delayed diagnosis is common. An AFF diagnostic software could provide timely AFF detection to prevent progression of incomplete or development of contralateral AFFs. In this study, we investigated the ability for an artificial intelligence (AI)-based application, using deep learning models (DLMs), particularly convolutional neural networks (CNNs), to detect AFFs from femoral radiographs. A labelled Australian dataset of pre-operative complete AFF (cAFF), incomplete AFF (iAFF), typical femoral shaft fracture (TFF), and non-fractured femoral (NFF) X-ray images in anterior-posterior view were used for training (N = 213, 49, 394, 1359, respectively). An AFFnet model was developed using a pretrained (ImageNet dataset) ResNet-50 backbone, and a novel Box Attention Guide (BAG) module to guide the model's scanning patterns to enhance its learning. All images were used to train and internally test the model using a 5-fold cross validation approach, and further validated by an external dataset. External validation of the model's performance was conducted on a Sweden dataset comprising 733 TFF and 290 AFF images. Precision, sensitivity, specificity, F1-score and AUC were measured and compared between AFFnet and a global approach with ResNet-50. Excellent diagnostic performance was recorded in both models (all AUC >0.97), however AFFnet recorded lower number of prediction errors, and improved sensitivity, F1-score and precision compared to ResNet-50 in both internal and external testing. Sensitivity in the detection of iAFF was higher for AFFnet than ResNet-50 (82 % vs 56 %). In conclusion, AFFnet achieved excellent diagnostic performance on internal and external validation, which was superior to a pre-existing model. Accurate AI-based AFF diagnostic software has the potential to improve AFF diagnosis, reduce radiologist error, and allow urgent intervention, thus improving patient outcomes.
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| 6. |
- Nguyen, Tho D. K., et al.
(författare)
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Quantitative Chemical Imaging at the Cellular Level: SIMS, Fluorescence, and Correlative Techniques
- 2022
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Ingår i: Single Cell ‘Omics of Neuronal Cells. - New York, NY : Springer US. - 0893-2336. ; , s. 219-250
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Bokkapitel (refereegranskat)abstract
- The cell is a heterogeneous chemical structure designed to accommodate its complex cellular functions in a living organism. Quantitative chemical imaging at the cellular level enables the investigation of the structural and functional molecular relation underlying cellular processes. We describe here the detailed methodology of the state-of-the-art secondary ion mass spectrometry (SIMS, NanoSIMS) and fluorescence microscopy (confocal, STED), along with selected examples for quantitative imaging at the cellular level. Correlative imaging that combines different imaging techniques is also demonstrated for selected applications in cell imaging. This chapter serves as a guideline assisting readers from unfamiliar fields of research to obtain reliable imaging at the cellular level while highlighting the strengths, limitations, and potentials of these technologies for cell imaging.
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| 7. |
- Nguyen, Tho D. K.
(författare)
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Quantitative chemical imaging to study content release from single nanovesicles
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cellular communication is vital for the survival of multicellular organisms. This process often relies on a highly regulated mechanism called exocytosis, which involves the release of chemical signals. During exocytosis, vesicles can fully or partially release their contents. The quantity of neurotransmitters expelled in different modes of release may have diverse effects on cellular communication by allowing cells to control the level of outgoing signals. Despite significant discoveries in understanding the components of exocytosis, there is still much to uncover regarding its regulation and implications. This thesis aims to gain a better understanding of vesicular content release, particularly in the context of partial release, using quantitative chemical imaging. This includes the integration of mass spectrometry imaging (MSI) with electron microscopy or electrochemical analysis alongside light microscopy. By doing so, a comprehensive approach can be employed to gain insights into the mechanism of vesicular content release and quantify the fraction of release. Electrochemical techniques offer the advantage of high temporal resolution and enable quantification of both stored and released molecules from vesicles. Coupled with imaging methods such as fluorescence, electron microscopy, and mass spectrometry imaging, comprehensive spatial information and chemical information can be obtained to complement the data provided by electrochemical techniques. In particular, nanoscale secondary ion mass spectrometry (NanoSIMS), a high-resolution MSI method that is capable of absolute quantification at subcellular level, was primarily used throughout this thesis. PC12 cells treated with isotopically labeled L-DOPA were examined, and NanoSIMS imaging was correlated with transmission electron microscopy (TEM) to detect and quantify the labeled dopamine in the halo and dense core compartments of large dense core vesicles (LDCVs) in paper I. Paper II introduced a dual-label approach to visualize and quantify vesicles undergoing partial release in PC12 cells by exposing them to a second label during exocytosis. Expanding on the dual-label approach, paper III investigated the influence of vesicle size on the dynamics of partial release. Furthermore, the combination of vesicle impact electrochemical cytometry (VIEC) with live fluorescence imaging was developed in paper IV allowing real-time analysis of vesicular content release from isolated labeled bovine chromaffin vesicles. Overall, these studies demonstrate the application of quantitative chemical imaging in understanding the mechanism and quantifying the fraction of release in vesicular content release.
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| 8. |
- Nguyen, Tho D. K., et al.
(författare)
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Quantitative Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) Imaging of Individual Vesicles to Investigate the Relation between Fraction of Chemical Release and Vesicle Size
- 2023
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Ingår i: Angewandte Chemie. - 0044-8249 .- 1521-3757. ; 62:28
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Tidskriftsartikel (refereegranskat)abstract
- We used correlative transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to quantify the contents of subvesicular compartments, and to measure the partial release fraction of C-13-dopamine in cellular nanovesicles as a function of size. Three modes of exocytosis comprise full release, kiss-and-run, and partial release. The latter has been subject to scientific debate, despite a growing amount of supporting literature. We tailored culturing procedures to alter vesicle size and definitively show no size correlation with the fraction of partial release. In NanoSIMS images, vesicle content was indicated by the presence of isotopic dopamine, while vesicles which underwent partial release were identified by the presence of an I-127-labelled drug, to which they were exposed during exocytosis allowing entry into the open vesicle prior to its closing again. Demonstration of similar partial release fractions indicates that this mode of exocytosis is predominant across a wide range of vesicle sizes.
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| 9. |
- Nguyen, Tho D. K., et al.
(författare)
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Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells
- 2022
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Ingår i: Acs Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:3, s. 4831-4842
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Tidskriftsartikel (refereegranskat)abstract
- For decades, "all-or-none"and "kiss-and-run"were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically. © 2022 The Authors. Published by American Chemical Society.
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| 10. |
- Rabasco, Stefania, et al.
(författare)
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Characterization of Stress Granule Protein Turnover in Neuronal Progenitor Cells Using Correlative STED and NanoSIMS Imaging
- 2023
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Stress granules (SGs) are stress-induced biomolecular condensates which originate primarily from inactivated RNA translation machinery and translation initiation factors. SG formation is an important defensive mechanism for cell survival, while its dysfunction has been linked to neurodegenerative diseases. However, the molecular mechanisms of SG assembly and disassembly, as well as their impacts on cellular recovery, are not fully understood. More thorough investigations into the molecular dynamics of SG pathways are required to understand the pathophysiological roles of SGs in cellular systems. Here, we characterize the SG and cytoplasmic protein turnover in neuronal progenitor cells (NPCs) under stressed and non-stressed conditions using correlative STED and NanoSIMS imaging. We incubate NPCs with isotopically labelled (15N) leucine and stress them with the ER stressor thapsigargin (TG). A correlation of STED and NanoSIMS allows the localization of individual SGs (using STED), and their protein turnover can then be extracted based on the 15N/14N ratio (using NanoSIMS). We found that TG-induced SGs, which are highly dynamic domains, recruit their constituents predominantly from the cytoplasm. Moreover, ER stress impairs the total cellular protein turnover regimen, and this impairment is not restored after the commonly proceeded stress recovery period.
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