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Lin, T.-C.

Publications and source records attributed to Lin, T.-C..

6 recordsLinked to original sources

Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure

Inhalation of airborne per- and polyfluoroalkyl substances (PFAS) represents an important yet understudied exposure route. While volatile organic compounds (VOCs) have been widely explored as biomarkers of toxicant exposure, their potential for early detection of PFAS-induced pulmonary toxicity remains largely unexplored. This study investigated VOC profiles in human alveolar (A549) and bronchial (BEAS-2B) epithelial cells following exposure to environmentally relevant PFAS concentrations (1, 5, and 10 ppb) for 12, 24, and 48 h. VOCs were analyzed using headspace solid-phase microextraction coupled with gas chromatography-Orbitrap mass spectrometry. We observed significant concentration- and time-dependent alterations in VOC profiles in both cell models. The principal VOCs associated with PFAS exposure include butanal, acetone, 2-butanone, 2-nonanone, (E)-2-nonenal, (E)-2-octenal, (E)-2-heptenal, 2,4-heptadienal, 2,4-nonadienal, 2,4-decadienal, 1-pentanol, and 1-hexanol. Cell type-specific regulations were observed, reflecting differential metabolic responses between transformed and non-transformed lung epithelial cells. Metabolite set enrichment analysis indicated perturbations in ketone body metabolism, consistent with altered cellular energy metabolism. Complementary qPCR analysis revealed altered expressions of CYP1A1, CYP2E1, ALDH1A1, and ALDH2, supporting a mechanistic link between PFAS exposure and oxidative stress, lipid peroxidation, and impaired aldehyde detoxification. These findings demonstrate that VOC profiling, combined with transcriptional analysis, can reveal PFAS-induced metabolic perturbations in pulmonary epithelial cells.

biochemistry↗

Resolving Orsay Virus δ Protein Architecture Using Molecular Rulers in Single-Molecule Force Spectroscopy

Understanding the mechanical stability and architecture of viral proteins can provide valuable information about their biological function, but it remains a significant biophysical challenge. This study employs single-molecule force spectroscopy (SMFS) to investigate the multi-domain architecture of the Orsay virus {delta} protein, which lacks repeat structures and exhibits weak unfolding peaks. We engineered a construct using titin (I27)4 domains as an internal molecular ruler, enabling us to bracket the {delta} protein peaks to determine domain length and identify unfolding forces with an atomic force microscope (AFM). To address limitations of one-dimensional (1D) force distributions in resolving overlapping structural states, we created a two-dimensional (2D) mechano-structural signature map. By plotting kinetic stability (unfolding force F) against physical structural footprint (domain length L), we distinguished distinct unfolding domains, successfully separating degenerate 1D data into two statistically distinct populations corresponding to the {delta} proteins internal domain (I) and C-terminal domain (C). This label-free method provides the first mechanical evidence of the {delta} proteins multi-domain architecture. It establishes a robust, multi-dimensional framework for decoding the mechanics of complex biomolecular assemblies in their native state.

biophysics↗

A genome and tissue-specific transcriptomes of the large-polyp coral, Fimbriaphyllia (Euphyllia) ancora: Recipe for a coral polyp

Coral "polyps" are composed of several tissues; however, their characteristics are largely unexplored. Here we report biological characteristics of the four tissues that comprise polyps: tentacle (Te), mesenterial filament (Me), body wall (Bo), and mouth with pharynx (MP), using comparative genomic, morpho-histological, and transcriptomic analyses of the large-polyp coral, Fimbriaphyllia ancora. A draft F. ancora genome assembly of 434 Mbp was created. Morpho-histological and transcriptomic characterization of the four tissues showed that they have distinct differences in structure, primary cellular composition, and transcriptional profiles. Tissue-specific, highly expressed genes (HEGs) of Te are related to biological defense, predation, and coral-algal symbiosis. Me expresses multiple digestive enzymes, whereas Bo expresses innate immunity and biomineralization-related molecules. Many receptors for neuropeptides and neurotransmitters are expressed in MP. The established dataset and new insights into tissue functions will facilitate a deeper understanding of coral biology.

genomics↗

Predicting splicing patterns from the transcription factor binding sites in the promoter with deep learning

BackgroundAlternative splicing is a crucial mechanism of post-transcriptional modification responsible for the transcriptome plasticity and proteome diversity of a metazoan cell. Although many splicing regulations around the exon/intron regions have been discovered, the relationship between promoter-bound transcription factors and the downstream alternative splicing remains largely unexplored. ResultsIn this study, we present computational approaches to decipher the regulation relationship connecting the promoter-bound transcription factor binding sites (TFBSs) and the splicing patterns. We curated a fine data set, including DNase I hypersensitive sites sequencing and transcriptome in fifteen human tissues from ENCODE. Specifically, we proposed different representations of TF binding context and splicing patterns to tackle the associations between the promoter and downstream splicing events. Our results demonstrated that the convolutional neural network (CNN) models learned from the TF binding changes in the promoter to predict the splicing pattern changes. Furthermore, through an in silico perturbation-based analysis of the CNN models, we identified several TFs that considerably reduced the model performance of splicing prediction. ConclusionIn conclusion, our finding highlights the potential role of promoter-bound TFBSs in influencing the regulation of downstream splicing patterns and provides insights for discovering alternative splicing regulations.

bioinformatics↗

Identification and comparative analysis of long non-coding RNAs in the brain of fire ant queens in two different reproductive states

BackgroundMany long non-coding RNAs (lncRNAs) have been extensively identified in many higher eukaryotic species. The function of lncRNAs has been reported to play important roles in diverse biological processes, including developmental regulation and behavioral plasticity. However, there are no reports of systematic characterization of long non-coding RNAs in the fire ant Solenopsis invicta. ResultsIn this study, we performed a genome-wide analysis of lncRNAs in the brains of S. invicta from RNA-seq. In total, 1,393 novel lncRNA transcripts were identified in the fire ant. In contrast to the annotated lncRNA transcripts having at least two exons, novel lncRNAs are monoexonic transcripts with a shorter length. Besides, the transcriptome from virgin alate and dealate mated queens were analyzed and compared. The results showed 295 differentially expressed mRNA genes (DEGs) and 65 differentially expressed lncRNA genes (DELs) between virgin and mated queens, of which 17 lncRNAs were highly expressed in the virgin alates and 47 lncRNAs were highly expressed in the mated dealates. By identifying the DEL:DEG pairs with high association in their expression (Spearmans |rho| > 0.8 and p-value < 0.01), many DELs were co-regulated with DEGs after mating. Furthermore, several remarkable lncRNAs (MSTRG.6523, MSTRG.588, and nc909) that were found to associate with particular coding genes may play important roles in the regulation of brain gene expression in reproductive transition in fire ants. ConclusionThis study provides the first genome-wide identification of S. invicta lncRNAs in the brains in different reproductive states and will contribute to a fuller understanding of the transcriptional regulation underpinning reproductive changes.

genomics↗

Stalk Lodging: A Portable Device for Phenotyping Stalk Bending Strength of Maize and Sorghum

BackgroundStalk lodging (breakage of plant stems prior to harvest) is a major problem for both farmers and plant breeders. A limiting factor in addressing this problem is the lack of a reliable method for phenotyping stalk strength. Previous methods of phenotyping stalk strength induce failure patterns different from those observed in natural lodging events. This paper describes a new device for field-based phenotyping of stalk strength called \"DARLING\" (Device for Assessing Resistance to Lodging IN Grains). The DARLING apparatus consists of a vertical arm which is connected to a horizontal footplate by a hinge. The operator places the device next to a stalk, aligns the stalk with a force sensor, steps on the footplate, and then pushes the vertical arm forward until the stalk breaks. Force and rotation are continuously recorded during the test and these quantities are used to calculate two quantities: stalk flexural stiffness and stalk bending strength.\n\nResultsField testing of DARLING was performed at multiple sites. Validation was based upon three factors. First, the device induces the characteristic \"crease\" or Brazier buckling failure patterns observed in naturally lodged stalks. Second, in agreement with prior research, flexural stiffness values attained using the DARLING apparatus are strongly correlated with bending strength measurements. Finally, a paired specimen experimental design was used to determine that the flexural data obtained with DARLING is in agreement with laboratory-based flexural testing results of the same specimens. DARLING was also deployed in the field to assess phenotyping throughput (# of stalks phenotyped per hour). Over approximately 5000 tests, the average testing rate was found to be 210 stalks/hour.\n\nConclusionsThe DARLING apparatus provides a quantitative assessment of stalk strength in a field setting. It induces the same failure patterns observed in natural lodging events. DARLING can also be used to perform non-destructive flexural tests. This new technology has many applications, including breeding, genetic studies on stalk strength, longitudinal studies of stalk flexural stiffness, and risk assessment of lodging propensity.

bioengineering↗