Integrative biology : quantitative biosciences from nano to macro最新文献

{"title":"Blue light effect on retinal pigment epithelial cells by display devices.","authors":"Jiyoung Moon,&nbsp;Jieun Yun,&nbsp;Yeo Dae Yoon,&nbsp;Sang-Il Park,&nbsp;Young-Jun Seo,&nbsp;Won-Sang Park,&nbsp;Hye Yong Chu,&nbsp;Keun Hong Park,&nbsp;Myung Yeol Lee,&nbsp;Chang Woo Lee,&nbsp;Soo Jin Oh,&nbsp;Young-Shin Kwak,&nbsp;Young Pyo Jang,&nbsp;Jong Soon Kang","doi":"10.1039/c7ib00032d","DOIUrl":"https://doi.org/10.1039/c7ib00032d","url":null,"abstract":"<p><p>Blue light has high photochemical energy and induces cell apoptosis in retinal pigment epithelial cells. Due to its phototoxicity, retinal hazard by blue light stimulation has been well demonstrated using high intensity light sources. However, it has not been studied whether blue light in the displays, emitting low intensity light, such as those used in today's smartphones, monitors, and TVs, also causes apoptosis in retinal pigment epithelial cells. We attempted to examine the blue light effect on human adult retinal epithelial cells using display devices with different blue light wavelength ranges, the peaks of which specifically appear at 449 nm, 458 nm, and 470 nm. When blue light was illuminated on A2E-loaded ARPE-19 cells using these displays, the display with a blue light peak at a shorter wavelength resulted in an increased production of reactive oxygen species (ROS). Moreover, the reduction of cell viability and induction of caspase-3/7 activity were more evident in A2E-loaded ARPE-19 cells after illumination by the display with a blue light peak at a shorter wavelength, especially at 449 nm. Additionally, white light was tested to examine the effect of blue light in a mixed color illumination with red and green lights. Consistent with the results obtained using only blue light, white light illuminated by display devices with a blue light peak at a shorter wavelength also triggered increased cell death and apoptosis compared to that illuminated by display devices with a blue light peak at longer wavelength. These results show that even at the low intensity utilized in the display devices, blue light can induce ROS production and apoptosis in retinal cells. Our results also suggest that the blue light hazard of display devices might be highly reduced if the display devices contain less short wavelength blue light.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"436-443"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00032d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34893370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein self-assembly following in situ expression in artificial and mammalian cells.","authors":"Urszula M Migas,&nbsp;Michelle K Quinn,&nbsp;Jennifer J McManus","doi":"10.1039/c6ib00240d","DOIUrl":"https://doi.org/10.1039/c6ib00240d","url":null,"abstract":"<p><p>The self-assembly of proteins has been widely studied in controlled in vitro conditions, and more recently in biological environments. The self-assembly of proteins in biology can be a feature of the pathogenesis of protein condensation disease, or can occur during normal physiological function, for example during the formation of intracellular non-membrane bound organelles. To determine the mechanisms for the assembly process fully, controlled in vitro experiments using purified protein solutions are often required. However, making direct connections between insights gathered from controlled experiments and those in complex biological environments remains a challenge. Using the P23T mutant of human γD-crystallin, a protein associated with congenital cataract, we have demonstrated that the equilibrium solubility boundary and solution behavior measured using phase diagrams of purified protein solutions is consistent with the assembly of the protein expressed in cell-free expression medium in artificial cells (without fluorescent labelling) and condensates formed in mammalian cells, thereby directly connecting in vitro measurements with those performed under physiological conditions.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"444-450"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c6ib00240d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34907968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative meta-modeling identifies endocytic vesicles, late endosome and the nucleus as the cellular compartments primarily directing RTK signaling.","authors":"Jared C Weddell,&nbsp;Princess I Imoukhuede","doi":"10.1039/c7ib00011a","DOIUrl":"https://doi.org/10.1039/c7ib00011a","url":null,"abstract":"<p><p>Recently, intracellular receptor signaling has been identified as a key component mediating cell responses for various receptor tyrosine kinases (RTKs). However, the extent each endocytic compartment (endocytic vesicle, early endosome, recycling endosome, late endosome, lysosome and nucleus) contributes to receptor signaling has not been quantified. Furthermore, our understanding of endocytosis and receptor signaling is complicated by cell- or receptor-specific endocytosis mechanisms. Therefore, towards understanding the differential endocytic compartment signaling roles, and identifying how to achieve signal transduction control for RTKs, we delineate how endocytosis regulates RTK signaling. We achieve this via a meta-analysis across eight RTKs, integrating computational modeling with experimentally derived cell (compartment volume, trafficking kinetics and pH) and ligand-receptor (ligand/receptor concentration and interaction kinetics) physiology. Our simulations predict the abundance of signaling from eight RTKs, identifying the following hierarchy in RTK signaling: PDGFRβ > IGFR1 > EGFR > PDGFRα > VEGFR1 > VEGFR2 > Tie2 > FGFR1. We find that endocytic vesicles are the primary cell signaling compartment; over 43% of total receptor signaling occurs within the endocytic vesicle compartment for these eight RTKs. Mechanistically, we found that high RTK signaling within endocytic vesicles may be attributed to their low volume (5.3 × 10^-19 L) which facilitates an enriched ligand concentration (3.2 μM per ligand molecule within the endocytic vesicle). Under the analyzed physiological conditions, we identified extracellular ligand concentration as the most sensitive parameter to change; hence the most significant one to modify when regulating absolute compartment signaling. We also found that the late endosome and nucleus compartments are important contributors to receptor signaling, where 26% and 18%, respectively, of average receptor signaling occurs across the eight RTKs. Conversely, we found very low membrane-based receptor signaling, exhibiting <1% of the total receptor signaling for these eight RTKs. Moreover, we found that nuclear translocation, mechanistically, requires late endosomal transport; when we blocked receptor trafficking from late endosomes to the nucleus we found a 57% reduction in nuclear translocation. In summary, our research has elucidated the significance of endocytic vesicles, late endosomes and the nucleus in RTK signal propagation.</p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"464-484"},"PeriodicalIF":2.5,"publicationDate":"2017-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c7ib00011a","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34938283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Active cytoskeletal force and chromatin condensation independently modulate intranuclear network fluctuations.","authors":"Stephen T Spagnol,&nbsp;Kris Noel Dahl","doi":"10.1039/c3ib40226f","DOIUrl":"https://doi.org/10.1039/c3ib40226f","url":null,"abstract":"<p><p>Chromatin remodeling, including the movement of genes and regulatory factors, precedes or accompanies stimulated changes in gene expression. Here we quantify chromatin fluctuations in primary human cells using particle-tracking microrheology and determine the physical mechanisms which influence chromatin reorganization. We find that intranuclear movements are enhanced beyond thermal motion by active force generation from cytoskeletal motor activity propagated through the LINC complex; intranuclear movements are also dependent on the viscoelasticity of the DNA-protein polymer network. Chromatin movements were dramatically altered by modulation of chromatin condensation state, which we independently verified using fluorescence lifetime imaging microscopy (FLIM). These findings suggest that chromatin condensation and cytoskeletal force generation play distinct functional roles in regulating intranuclear movements, and these effects are decoupled as measured by particle tracking. We further utilize this approach in identifying the nuclear responsiveness of primary human endothelial cells to vascular endothelial growth factor (VEGF): early in the response chromatin movements increase and are dominated by cytoskeletal force, which transitions at later times to a chromatin decondensation event. Given the hierarchical genome organization in primary cells, our work generally suggests an important role for force generation and chromatin mechanics in altered gene expression kinetics. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"523-31"},"PeriodicalIF":2.5,"publicationDate":"2014-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40226f","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40301246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A quantum dot-based microfluidic multi-window platform for quantifying the biomarkers of breast cancer cells.","authors":"Seyong Kwon,&nbsp;Minseok S Kim,&nbsp;Eun Sook Lee,&nbsp;Jang Sihn Sohn,&nbsp;Je-Kyun Park","doi":"10.1039/c3ib40224j","DOIUrl":"https://doi.org/10.1039/c3ib40224j","url":null,"abstract":"<p><p>Conventional molecular profiling methods using immunochemical assays have limits in terms of multiplexity and the quantification of biomarkers in investigation of cancer cells. In this paper, we demonstrate a quantum dot (QD)-based microfluidic multiple biomarker quantification (QD-MMBQ) method that enables labeling of more than eight proteins immunochemically on cell blocks within 1 h, in a quantitative manner. An internal reference, β-actin, was used as a loading control to compensate for differences in not only the cell number but also in staining quality among specimens. Furthermore, the microfluidic blocking method exhibited less nonspecific binding of QDs than the conventional static blocking method. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"430-7"},"PeriodicalIF":2.5,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40224j","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40287200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting essential genes in prokaryotic genomes using a linear method: ZUPLS.","authors":"Kai Song,&nbsp;Tuopong Tong,&nbsp;Fang Wu","doi":"10.1039/c3ib40241j","DOIUrl":"https://doi.org/10.1039/c3ib40241j","url":null,"abstract":"<p><p>An effective linear method, ZUPLS, was developed to improve the accuracy and speed of prokaryotic essential gene identification. ZUPLS only uses the Z-curve and other sequence-based features. Such features can be calculated readily from the DNA/amino acid sequences. Therefore, no well-studied biological network knowledge is required for using ZUPLS. This significantly simplifies essential gene identification, especially for newly sequenced species. ZUPLS can also select necessary features automatically by embedding the uninformative variable elimination tool into the partial least squares classifier. No optimized modelling parameters are needed. ZUPLS has been used, herein, to predict essential genes of 12 remotely related prokaryotes to test its performance. The cross-organism predictions yielded AUC (Area Under the Curve) scores between 0.8042 and 0.9319 by using E. coli genes as the training samples. Similarly, ZUPLS achieved AUC scores between 0.8111 and 0.9371 by using B. subtilis genes as the training samples. We also compared it with the best available results of the existing approaches for further testing. The improvement of the AUC score in predicting B. subtilis essential genes using E. coli genes was 0.13. Additionally, in predicting E. coli essential genes using P. aeruginosa genes, the significant improvement was 0.10. Similarly, the exceptional improvement of the average accuracy of M. pulmonis using M. genitalium and M. pulmonis genes was 14.7%. The combined superior feature extraction and selection power of ZUPLS enable it to give reliable prediction of essential genes for both Gram-positive/negative organisms and rich/poor culture media. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"460-9"},"PeriodicalIF":2.5,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40241j","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40289951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A microfluidic-based genetic screen to identify microbial virulence factors that inhibit dendritic cell migration.","authors":"Laura M McLaughlin,&nbsp;Hui Xu,&nbsp;Sarah E Carden,&nbsp;Samantha Fisher,&nbsp;Monique Reyes,&nbsp;Sarah C Heilshorn,&nbsp;Denise M Monack","doi":"10.1039/c3ib40177d","DOIUrl":"https://doi.org/10.1039/c3ib40177d","url":null,"abstract":"<p><p>Microbial pathogens are able to modulate host cells and evade the immune system by multiple mechanisms. For example, Salmonella injects effector proteins into host cells and evades the host immune system in part by inhibiting dendritic cell (DC) migration. The identification of microbial factors that modulate normal host functions should lead to the development of new classes of therapeutics that target these pathways. Current screening methods to identify either host or pathogen genes involved in modulating migration towards a chemical signal are limited because they do not employ stable, precisely controlled chemical gradients. Here, we develop a positive selection microfluidic-based genetic screen that allows us to identify Salmonella virulence factors that manipulate DC migration within stable, linear chemokine gradients. Our screen identified 7 Salmonella effectors (SseF, SifA, SspH2, SlrP, PipB2, SpiC and SseI) that inhibit DC chemotaxis toward CCL19. This method is widely applicable for identifying novel microbial factors that influence normal host cell chemotaxis as well as revealing new mammalian genes involved in directed cell migration. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"438-49"},"PeriodicalIF":2.5,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40177d","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40287327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T cells sense biophysical cues using lamellipodia and filopodia to optimize intraluminal path finding.","authors":"Kwang Hoon Song,&nbsp;Keon Woo Kwon,&nbsp;Jong-Cheol Choi,&nbsp;Jaehwang Jung,&nbsp;Yongkeun Park,&nbsp;Kahp-Yang Suh,&nbsp;Junsang Doh","doi":"10.1039/c4ib00021h","DOIUrl":"https://doi.org/10.1039/c4ib00021h","url":null,"abstract":"<p><p>Intraluminal crawling is considered to be important for extravasation of leukocytes in blood vessels, but biochemical/biophysical cues guiding the crawling of leukocytes have not been clearly understood. Here we provide evidence that T cells sense the topography of luminal surfaces and the nuclei of endothelial cells (ECs) using lamellipodia and filopodia, respectively, to optimize path finding during intraluminal crawling. Well-aligned EC layers or replicas of EC layers, which exhibit topography similar to that of EC layers, were fabricated, and flow was applied either parallel or perpendicular to the orientation of EC alignment. T cells crawled along the valleys of the topographical landscapes of the EC layers, while avoiding nuclei of ECs regardless of flow direction. Pharmacological inhibitor treatments revealed that sensing of topography and nuclei of EC layers was mediated by lamellipodia and filopodia, respectively. Lamellipodia or filopodia-inhibited T cells crawled significantly longer distances for extravasation than did normal T cells, indicating that sensing biophysical cues are critical for optimizing routes for extravasation. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"450-9"},"PeriodicalIF":2.5,"publicationDate":"2014-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c4ib00021h","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40286573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folate conjugated silk fibroin nanocarriers for targeted drug delivery.","authors":"Bano Subia,&nbsp;Sourov Chandra,&nbsp;Sarmistha Talukdar,&nbsp;Subhas C Kundu","doi":"10.1039/c3ib40184g","DOIUrl":"https://doi.org/10.1039/c3ib40184g","url":null,"abstract":"<p><p>Disease treatment processes mainly focus on the development of nontoxic, biodegradable, non-immunogenic, biocompatible materials capable of controlled and long-term release of biomolecules. In this work silk protein fibroin from non-mulberry tropical tasar silkworm, Antheraea mylitta, is used to prepare nanoparticles as a drug delivery system. Folate is a vitamin, which is brought into healthy and cancerous cells by folate receptors. The efficiency of silk fibroin-folate nanoparticles loaded with anticancer drug doxorubicin was evaluated by analysing the cell viability, proliferation and endocytosis. Consequently the effects of pro-inflammatory responses by cytokines such as TNF-α, IL-1β and nitric oxide were checked by stimulating the macrophages with folate conjugated silk fibroin nanoparticles. The fibroin-folate nanocarriers are nontoxic, easily taken up by cells and capable of sustained drug release. Nanoparticles loaded with anticancer drug doxorubicin target cancer cells. The results show that silk fibroin-folate nanoparticles may serve as promising nanocarriers for different biomedical and nanotechnology applications in cancer research. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"203-14"},"PeriodicalIF":2.5,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40184g","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31961122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrotaxis of human neutrophils during mechanical confinement inside microfluidic channels.","authors":"Bashar Hamza,&nbsp;Elisabeth Wong,&nbsp;Sachin Patel,&nbsp;Hansang Cho,&nbsp;Joseph Martel,&nbsp;Daniel Irimia","doi":"10.1039/c3ib40175h","DOIUrl":"https://doi.org/10.1039/c3ib40175h","url":null,"abstract":"<p><p>The current paradigm of unidirectional migration of neutrophils from circulation to sites of injury in tissues has been recently challenged by observations in zebrafish showing that neutrophils can return from tissues back into the circulation. However, the relevance of these observations to human neutrophils remains unclear, the forward and reverse migration of neutrophils is difficult to quantify, and the precise conditions modulating the reverse migration cannot be isolated. Here, we designed a microfluidic platform inside which we observed human neutrophil migration in response to chemoattractant sources inside channels, simulating the biochemical and mechanical confinement conditions at sites of injury in tissues. We observed that, after initially following the direction of chemoattractant gradients, more than 90% of human neutrophils can reverse their direction and migrate persistently and for distances longer than one thousand micrometers away from chemoattractant sources (retrotaxis). Retrotaxis is enhanced in the presence of lipoxin A4 (LXA4), a well-established mediator of inflammation resolution, or Tempol, a standard antioxidant. Retrotaxis stops after neutrophils encounter targets which they phagocytise or on surfaces presenting high concentrations of fibronectin. Our microfluidic model suggests a new paradigm for neutrophil accumulation at sites of inflammation, which depends on the balance of three simultaneous processes: chemotaxis along diffusion gradients, retrotaxis following mechanical guides, and stopping triggered by phagocytosis. </p>","PeriodicalId":520649,"journal":{"name":"Integrative biology : quantitative biosciences from nano to macro","volume":" ","pages":"175-83"},"PeriodicalIF":2.5,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/c3ib40175h","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32024304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}