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Single-cell transcriptomics uncovers EGFR signaling-mediated gastric progenitor cell differentiation in stomach homeostasis (vol 14, 3750, 2023)

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NATURE COMMUNICATIONS 2023年第1期14卷 1-16页

作者： Takada, Hitomi Sasagawa, Yohei Yoshimura, Mika Tanaka, Kaori Iwayama, Yoshimi Hayashi, Tetsutaro Isomura-Matoba, Ayako Nikaido, Itoshi Kurisaki, Akira Laboratory of Stem Cell Technologies Graduate School of Science and Technology Nara Institute of Science and Technology Takayama-cho Ikoma Nara Japan Laboratory for Bioinformatics Research RIKEN Center for Biosystems Dynamics Research Wako Saitama Japan Department of Functional Genome Informatics Biological Data Science Medical Research Institute Tokyo Medical and Dental University Bunkyo Tokyo Japan Master’s/Doctoral Program in Life Science Innovation (Bioinformatics) Degree Programs in Systems and Information Engineering Graduate School of Science and Technology University of Tsukuba Tsukuba Ibaraki Japan

Defects in gastric progenitor cell differentiation are associated with various gastric disorders, including atrophic gastritis, intestinal metaplasia, and gastric cancer. However, the mechanisms underlying the multilineage differentiation of gastric progenitor cells during healthy homeostasis remain poorly understood. Here, using a single-cell RNA sequencing method, Quartz-Seq2, we analyzed the gene expression dynamics of progenitor cell differentiation toward pit cell, neck cell, and parietal cell lineages in healthy adult mouse corpus tissues. Enrichment analysis of pseudotime-dependent genes and a gastric organoid assay revealed that EGFR-ERK signaling promotes pit cell differentiation, whereas NF-κB signaling maintains gastric progenitor cells in an undifferentiated state. In addition, pharmacological inhibition of EGFR in vivo resulted in a decreased number of pit cells. Although activation of EGFR signaling in gastric progenitor cells has been suggested as one of the major inducers of gastric cancers, our findings unexpectedly identified that EGFR signaling exerts a differentiation-promoting function, not a mitogenic function, in normal gastric homeostasis.

关键词： Adult stem cells Stem-cell differentiation Stem-cell niche

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One-step flow synthesis of size-controlled polymer nanogels in a fluorocarbon microfluidic chip

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RSC Advances 2024年第16期14卷 11258-11265页

作者： Montalbo, Reynaldo Carlos K. Wu, Meng-Jie Tu, Hsiung-Lin Institute of Chemistry Academia Sinica Taipei11529 Taiwan Nanoscience and Technology Taiwan International Graduate Program Academia Sinica Taipei11529 Taiwan Department of Engineering and System Science National Tsing-Hua University Hsinchu300044 Taiwan Department of Chemistry National Cheng-Kung University Tainan70101 Taiwan Genome and Systems Biology Degree Program Academia Sinica and National Taiwan University Taiwan

Synthetic polymer nanoparticles (NPs) with biomimetic properties are ideally suited for different biomedical applications such as drug delivery and direct therapy. However, bulk synthetic approaches can suffer from poor reproducibility and scalability when precise size control or multi-step procedures are required. Herein, we report an integrated microfluidic chip for the synthesis of polymer NPs. The chip could sequentially perform homopolymer synthesis and subsequent crosslinking into NPs without intermediate purification. This was made possible by fabrication of the chip with a fluorinated elastomer and incorporation of two microfluidic mixers. The first was a long channel with passive mixing features for the aqueous RAFT synthesis of stimuli-responsive polymers in ambient conditions. The polymers were then directly fed into a hydrodynamic flow focusing (HFF) junction that rapidly mixed them with a crosslinker solution to produce NPs. Compared to microfluidic systems made of PDMS or glass, our chip had better compatibility and facile fabrication. The polymers were synthesized with high monomer conversion and the NP size was found to be influenced by the flow rate ratio between the crosslinker solution and polymer solution. This allowed for the size to be predictably controlled by careful adjustment of the fluid flow rates. The size of the NPs and their stimuli-responses were studied using DLS and SEM imaging. This microfluidic chip design can potentially streamline and provide some automation for the bottom-up synthesis of polymer NPs while offering on-demand size control. © 2024 The Royal Society of Chemistry.

关键词： Microfluidic chips

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Folding angle and wing flexibility influence the flight performance of origami winged fruits

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Nonlinear Dynamics 2024年第13期112卷 10995-11011页

作者： Cai, Jing-Fang Hsu, Ya-Chun Yen, Yu-Chen Lee, Yun-Chung Peyton, Bernie Huang, Mei-Jiau Yu, Hon-Tsen Juang, Jia-Yang Department of Mechanical Engineering National Taiwan University Taipei106319 Taiwan Department of Life Science National Taiwan University Taipei106319 Taiwan Berkeley CA United States Program in Nanoengineering and Nanoscience Graduate School of Advanced Technology National Taiwan University Taipei106319 Taiwan Degree Program of Genome and Systems Biology National Taiwan University Taipei106319 Taiwan

Winged fruits possess a unique flight mechanism relying on simple geometric structures rather than neuromuscular control. This study proposes an innovative approach using origami techniques to create three-winged model fruits, serving as a proxy for understanding the flight dynamics of natural winged fruits. Paper is employed to simulate inherent wing flexibility, with the option to add plastic frames for rigidity. We comprehensively investigate the free fall motion of both rigid and flexible winged fruits through experimental and numerical analyses. Velocity–time curves reveal a three-stage descent pattern—acceleration, deceleration, and steady states. The overshoot phenomenon is attributed to rapid lift increase due to leading-edge vortices attaching stably to the wings. This insight sheds light on aerodynamics governing fruit flight. Compared with rigid wings, flexible wings exhibit two key properties—slower descent and higher self-orienting capability—that facilitate a more stable and longer-distance dispersal of seeds under crosswind conditions. Our study demonstrates the potential benefits of flexible wings in natural seed distribution. This study advances our understanding of winged fruit flight dynamics, utilizing origami as a powerful tool for biomimetic investigations. The findings have broad implications, from improving aerodynamic designs to developing efficient micro air vehicles and electronic microfliers, and understanding seed dispersal evolution. Graphical abstract: (Figure presented.). © The Author(s), under exclusive licence to Springer Nature B.V. 2024.

关键词： Fruits

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Meiosis in male Drosophila

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Spermatogenesis 2012年第3期2卷 167-184页

作者： Bruce D McKee Rihui Yan Jui-He Tsai Department of Biochemistry Cellular & Molecular Biology University of Tennessee Knoxville TN USA Genome Science and Technology Program Knoxville TN USA.

Meiosis entails sorting and separating both homologous and sister chromatids. The mechanisms for connecting sister chromatids and homologs during meiosis are highly conserved and include specialized forms of the cohesin complex and a tightly regulated homolog synapsis/recombination pathway designed to yield regular crossovers between homologous chromatids. Drosophila male meiosis is of special interest because it dispenses with large segments of the standard meiotic script, particularly recombination, synapsis and the associated structures. Instead, Drosophila relies on a unique protein complex composed of at least two novel proteins, SNM and MNM, to provide stable connections between homologs during meiosis I. Sister chromatid cohesion in Drosophila is mediated by cohesins, ring-shaped complexes that entrap sister chromatids. However, unlike other eukaryotes Drosophila does not rely on the highly conserved Rec8 cohesin in meiosis, but instead utilizes two novel cohesion proteins, ORD and SOLO, which interact with the SMC1/3 cohesin components in providing meiotic cohesion.

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The emerging field of clinical Bioinformatics: Infrastructure, analytical tools, and knowledge bases 4

The emerging field of clinical Bioinformatics: Infrastructur...

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4th International Conference on Advances in Biomedical Engineering, ICABME 2017

作者： Abouelhoda, Mohamed Systems and Biomedical Engineering Department Cairo University Giza Egypt Saudi Human Genome Program King Abdulaziz City for Science and Technology Riyadh Saudi Arabia King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia

ISBN: (纸本)9781538616420

The availability of cost effective and fast genome sequencing techniques has paved the way for a personalized medical practice. The new sequencing technology produces huge datasets with different characteristics and the analysis has evolved from a single program to a workflow of tens of analytical steps, starting from the analysis of raw data until generating clinical reports. The mix between big data, analysis workflows, and clinical requirements has shaped the field of clinical bioinformatics. In this paper, we review the basic components of this field, including computational infrastructure, analytical workflows, and knowledge bases for interpretation of results and for reaching clinical decisions. © 2017 IEEE.

关键词： Bioinformatics

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Comparison of threshold selection methods for microarray gene co-expression matrices

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BMC Research Notes 2009年第1期2卷 1-6页

作者： Borate, Bhavesh Chesler, Elissa Langston, Michael Saxton, Arnold Voy, Brynn Genome Science and Technology Program University of Tennessee Knoxville TN United States Department of Electrical Engineering and Computer Science University of Tennessee Knoxville TN United States Oak Ridge National Laboratory Systems Genetics Group Biosciences Division Oak Ridge TN United States Department of Animal Science University of Tennessee Knoxville TN United States

Background. Network and clustering analyses of microarray co-expression correlation data often require application of a threshold to discard small correlations, thus reducing computational demands and decreasing the number of uninformative correlations. This study investigated threshold selection in the context of combinatorial network analysis of transcriptome data. Findings. Six conceptually diverse methods - based on number of maximal cliques, correlation of control spots with expressed genes, top 1% of correlations, spectral graph clustering, Bonferroni correction of p-values, and statistical power - were used to estimate a correlation threshold for three time-series microarray datasets. The validity of thresholds was tested by comparison to thresholds derived from Gene Ontology information. Stability and reliability of the best methods were evaluated with block bootstrapping. Two threshold methods, number of maximal cliques and spectral graph, used information in the correlation matrix structure and performed well in terms of stability. Comparison to Gene Ontology found thresholds from number of maximal cliques extracted from a co-expression matrix were the most biologically valid. Approaches to improve both methods were suggested. Conclusion. Threshold selection approaches based on network structure of gene relationships gave thresholds with greater relevance to curated biological relationships than approaches based on statistical pair-wise relationships. © 2009 Saxton et al;licensee BioMed Central Ltd.

关键词： Spectral Cluster Maximal Clique Threshold Estimate Biological Relationship Spectral Graph

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Chromatograms and Mass Spectra of High-Mannose and Paucimannose N-Glycans for Rapid Isomeric Identifications

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Journal of Proteome Research 2024年第3期23卷 939-955页

作者： Liew, Chia Yen Chen, Jien-Lian Lin, Yen-Ting Luo, Hong-Sheng Hung, An-Ti Magoling, Bryan John Abel Nguan, Hock-Seng Lai, Charles Pin-Kuang Ni, Chi-Kung Institute of Atomic and Molecular Sciences Academia Sinica Taipei 106216 Taiwan International Graduate Program of Molecular Science and Technology National Taiwan University Taipei 106216 Taiwan Molecular Science and Technology Taiwan International Graduate Program Academia Sinica Taipei 106216 Taiwan Department of Chemistry National Taiwan Normal University Taipei 116059 Taiwan Department of Chemistry National Tsing Hua University Hsinchu 300044 Taiwan Institute of Biochemical Sciences College of Life Science National Taiwan University Taipei 106216 Taiwan Chemical Biology and Molecular Biophysics Program Taiwan International Graduate Program Academia Sinica Taipei 115201 Taiwan Genome and Systems Biology Degree Program National Taiwan University and Academia Sinica Taipei 106216 Taiwan

N-Linked glycosylation is one of the most essential post-translational modifications of proteins. However, N-glycan structural determination remains challenging because of the small differences in structures between isomers. In this study, we constructed a database containing collision-induced dissociation MSⁿ mass spectra and chromatograms of high-performance liquid chromatography for the rapid identification of high-mannose and paucimannose N-glycan isomers. These N-glycans include isomers by breaking of arbitrary numbers of glycosidic bonds at arbitrary positions of canonical Man₉GlcNAc₂ N-glycans. In addition, some GlcMan_nGlcNAc₂ N-glycan isomers were included in the database. This database is particularly useful for the identification of the N-glycans not in conventional N-glycan standards. This study demonstrated the application of the database to structural assignment for high-mannose N-glycans extracted from bovine whey proteins, soybean proteins, human mammary epithelial cells, and human breast carcinoma cells. We found many N-glycans that are not expected to be generated by conventional biosynthetic pathways of multicellular eukaryotes. © 2024 The Authors. Published by American Chemical Society.

关键词： bovine whey protein chromatogram CID spectra high-mannose N-glycans human breast carcinoma cell human mammary epithelial cell LODES/MSn logically derived sequence tandem mass spectrometry soybean protein structure

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Systematic use of computational methods allows stratification of treatment responders in glioblastoma multiforme

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Systems Biomedicine 2013年第2期1卷 130-136页

作者： Riku Louhimo Viljami Aittom?ki Ali Faisal Marko Laakso Ping Chen Kristian Ovaska Erkka Valo Leo Lahti Vladimir Rogojin Samuel Kaski Sampsa Hautaniemi* Systems Biology Laboratory Genome-scale Biology Research Program University of Helsinki Helsinki Institute of Information Technology (HIIT) Department of Information and Computer Science Aalto University

Background:Cancers are complex diseases whose comprehensive characterization requires genome-scale molecular data at multiple levels from genetics to transcriptomics and clinical data. Using our recently published Anduril bioinformatics framework and novel computational approaches, such as dependency analysis, we identify key variables at miRNA, copy number variation, expression, methylation, and pathway levels in glioblastoma multiforme (GBM) progression and drug resistance. Furthermore, we identify characteristics of clinically relevant subgroups, such as patients treated with temozolomide and patients with an EGFRvIII mutation, which is a constitutively active variant of ***:We identify several novel genomic regions and transcript profiles that may contribute to GBM progression and drug resistance. All results and Anduril scripts are available at http://***/camda/.Conclusions:Our results highlight the need for approaches that define context at several levels in order to identify genomic regions or transcript profiles playing key roles in cancer progression and drug resistance.

关键词： data integration data mining dependency analysis

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The probability distribution for a random match between an experimental-theoretical spectral pair in tandem mass spectrometry

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Journal of Bioinformatics and Computational Biology 2005年第2期3卷 455-476页

作者： Fridman, Tema Razumovskaya, Jane Verberkmoes, Nathan Hurst, Greg Protopopescu, Vladimir Xu, Ying Joint Institute for Computer Science University of Tennessee/ORNL ORNL Oak Ridge TN 37831-6164 PO Box 2008 United States Genome Science/Technology Program University of Tennessee Life Sciences Division Oak Ridge TN 37831-6164 United States Genome Science/Technology Program University of Tennessee Chemical Sciences Division Oak Ridge TN 37831-6131 United States Chemical Sciences Division Oak Ridge National Laboratory Oak Ridge TN 37831-6131 United States Computer Sci./Mathematics Division Oak Ridge National Laboratory Oak Ridge TN 37831-6164 United States Biochem./Molecular Biol. Department University of Georgia Athens GA 30602 United States

Proteomic techniques are fast becoming the main method for qualitative and quantitative determination of the protein content in biological systems. Despite notable advances, efficient and accurate analysis of high throughput proteomic data generated by mass spectrometers remains one of the major stumbling blocks in the protein identification problem. We present a model for the number of random matches between an experimental MS-MS spectrum and a theoretical spectrum of a peptide. The shape of the probability distribution is a function of the experimental accuracy, the number of peaks in the experimental spectrum, the length of the interval over which the peaks are distributed, and the number of theoretical spectral peaks in this interval. Based on this probability distribution, a goodness-of-fit tool can be used to yield fast and accurate scoring schemes for peptide identification through database search. In this paper, we describe one possible implementation of such a method and compare the performance of the resulting scoring function with that of SEQUEST. In terms of speed, our algorithm is roughly two orders of magnitude faster than the SEQUEST program, and its accuracy of peptide identification compares favorably to that of SEQUEST. Moreover, our algorithm does not use information related to the intensities of the peaks. © Imperial College Press.

关键词： Database search Mass spectrometry Tandem

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Microfractures in TiO2Enhance the Photoelectrochemical Properties of Photosystem i Bio-Sensitized Solar Cells 5

Microfractures in TiO2Enhance the Photoelectrochemical Prope...

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5th IEEE International Conference on BioInspired Processing, BIP 2023

作者： Flores, Sebastian Castro Araya, Christopher Espinoza Segura, Fabricio Chaverri Pineda, Leslie W. Bruce, Barry D. Villarreal, Claudia C. Cartago Costa Rica Maestria Ingenieria en Dispositivos Medicos Cartago Costa Rica San Jose Costa Rica University of Tennessee Department of Biochemistry Cellular and Molecular Biology Program in Genome Science and Technology KnoxvilleTN United States San Jose Costa Rica

ISBN: (纸本)9798350330052

Climate change, caused by the increasing energy demand from fossil fuels due to population growth and economic expansion, triggers the need for clean, renewable, and sustainable energy sources. The solar energy contributes to approximately 99.9% of the Earth's energy. Therefore, photovoltaic technology is considered a possible substitute for fossil fuels owing to its abundance, but the current silicon and thin film photovoltaic (PV) technologies generate greenhouse gas emissions (GHE) during manufacturing and use scarce and polluting materials. Bio-sensitized solar cells (BSSCs) offer a promising solution using simple, lower energy-demand manufacturing processes and abundant, non-toxic materials. BSSCs are derived from dye-sensitized solar cells (DSSCs) technology by replacing the synthetic dye with biological molecules, such as photosystem I (PSI), into a thin film device. We report a BSSC using PSI as a sensitizer, TiO2 as a wide-bandgap semiconductor, Co-bipyridine compound as a redox mediator in the electrolyte, and PEDOT-CNT composite as the counter electrode. This study investigates how microfractures on the TiO2 thin film induced during thermal sintering affect the photoelectrochemical performance of the BSSCs. Electrochemical characterization of the PSI-BSSCs was performed under a solar simulator using linear sweep voltammetry (LSV), open-circuit voltage decay (OCVD), chronoamperometry, and electrochemical impedance spectroscopy (EIS). SEM micrographs reveal fissures in the photoanode surface induced by the fast heating and cooling during thermal treatments. Surprisingly, the microfractures improved the performance of the solar cells and will be discussed regarding the accessibility of PSI and the mediator to penetrate the nanostructured electrode and enhance the photocurrents generated. The BSSCs improvement due to the microfractures is ascribed to the enabled diffusion of the PSI sensitizer through the nanoporous TiO2, given the significantly larger size o

关键词： bio-sensitized solar cell microfractures photosystem I surface area TiO2 photoanodes

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