The histone acetyltransferase Dmel\TIP60 Is essential for multicellular development in Drosophila

Combinatorial histone modifications control chromatin packaging which in turn, contributes to the precise patterning of gene expression during development. Histone acetyltransferases (HATs) are a key class of chromatin regulatory proteins that mediate such developmental chromatin control; however their specific roles during multicellular development remain unclear. Here, we report the first isolation and developmental characterization of a Drosophila HAT gene (Dmel\TIP60) that is the homolog of the human HAT gene TIP60. We show that Dmel\TIP60 is differentially expressed during Drosophila development, with transcript levels significantly peaking during embryogenesis. We further demonstrate that reducing endogenous Dmel\TIP60 expression in Drosophila embryonic cells by RNAi results in cellular defects and lethality. Finally, we use our Drosophila GAL4 inducible Dmel\TIP60 knockdown/overexpression system to explore the role of Dmel\TIP60 in a wide variety of specific tissues during Drosophila development. We show that ubiquitous and cell/tissue specific reduction of Dmel\TIP60 expression results in lethality and/or cell/tissue specific phenotypes during fly development. Loss of Dmel\TIP60 in the wing leads to a range of wing abnormalities, including the formation of wing blisters in the most severe cases. Wing surface area and cell count/hair density assays reveal that although the number of cells that compose the wing remain unaffected, their size is significantly smaller than normal and there are defects in wing cell planer polarity. Additionally, we find that loss of Dmel\TIP60 in the CNS leads to lethality and a substantial loss of differentiated neurons in the larval brain, while cyclin E levels and apoptosis remain unaffected. Finally, we show that loss of Dmel\TIP60 in the mesoderm leads to lethality, and malformation or absence of the muscle fibers in the developing embryo. Overexpression of Dmel\TIP60 in each of these tissues has no affect on their development. Taken together, our results support an essential role for Dmel\TIP60 in the differentiation and formation of a variety of specific cell and tissue types. Significantly, our inducible and targeted HAT knockdown system in Drosophila now provides a powerful tool to effectively study the roles of these chromatin mediators in specific tissues and cell types during development.Ph.D., Biology -- Drexel University, 200

Orbital angular momentum mode-demultiplexing scheme with partial angular receiving aperture

For long distance orbital angular momentum (OAM) based transmission, the conventional whole beam receiving scheme encounters the difficulty of large aperture due to the divergence of OAM beams. We propose a novel partial receiving scheme, using a restricted angular aperture to receive and demultiplex multi-OAM-mode beams. The scheme is theoretically analyzed to show that a regularly spaced OAM mode set remain orthogonal and therefore can be de-multiplexed. Experiments have been carried out to verify the feasibility. This partial receiving scheme can serve as an effective method with both space and cost savings for the OAM communications. It is applicable to both free space OAM optical communications and radio frequency (RF) OAM communications

Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.

Retinal degeneration often results in the loss of light-sensing photoreceptors, which leads to permanent vision loss. Generating transplantable retinal photoreceptors using human somatic cell-derived induced pluripotent stem cells (iPSCs) holds promise to treat a variety of retinal degenerative diseases by replacing the damaged or dysfunctional native photoreceptors with healthy and functional ones. Establishment of effective methods to produce retinal cells including photoreceptors in chemically defined conditions using current Good Manufacturing Practice (cGMP)-manufactured human iPSC lines is critical for advancing cell replacement therapy to the clinic. In this study, we used a human iPSC line (NCL-1) derived under cGMP-compliant conditions from CD34+ cord blood cells. The cells were differentiated into retinal cells using a small molecule-based retinal induction protocol. We show that retinal cells including photoreceptors, retinal pigmented epithelial cells and optic cup-like retinal organoids can be generated from the NCL-1 iPSC line. Additionally, we show that following subretinal transplantation into immunodeficient host mouse eyes, retinal cells successfully integrated into the photoreceptor layer and developed into mature photoreceptors. This study provides strong evidence that transplantable photoreceptors can be generated from a cGMP-manufactured human iPSC line for clinical applications. Stem Cells Translational Medicine 2018;7:210-219

Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism

Background: Tip60 is a key histone acetyltransferase (HAT) enzyme that plays a central role in diverse biological processes critical for general cell function; however, the chromatin-mediated cell-type specific developmental pathways that are dependent exclusively upon the HAT activity of Tip60 remain to be explored. Methods and Findings: Here, we investigate the role of Tip60 HAT activity in transcriptional control during multicellular development in vivo by examining genome-wide changes in gene expression in a Drosophila model system specifically depleted for endogenous dTip60 HAT function. Conclusions: We show that amino acid residue E431 in the catalytic HAT domain of dTip60 is critical for the acetylation of endogenous histone H4 in our fly model in vivo, and demonstrate that dTip60 HAT activity is essential for multicellular development. Moreover, our results uncover a novel role for Tip60 HAT activity in controlling neuronal specific gene expression profiles essential for nervous system function as well as a central regulatory role for Tip60 HAT function in general metabolism

Simultaneous profiling of transcriptome and DNA methylome from a single cell.

BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation

Psychological Capital, Positive Affect, and Organizational Outcomes: A Three-Wave Cross-Lagged Study

Psychological capital (PsyCap) is a higher-order construct comprising hope, efficacy, optimism, and resiliency, which has attracted more and more attention from both academics and practitioners. Despite promising progress made in the PsyCap literature, the underlying mechanisms linking PsyCap to organizational outcomes still need more investigation utilizing longitudinal research design. Moreover, the reciprocal relationships between PsyCap and positive affect require more attention. Therefore, we aim to test the central role of positive affect in the relationships between PsyCap and affective organizational commitment (AOC) on one hand and organizational citizenship behaviour toward organization (OCBO) on the other hand as well as the reciprocal relationships between PsyCap and positive affect in this study. A three-wave longitudinal survey was conducted using a cross-lagged panel design with a one-month time lag between two consecutive waves. Panel data was collected from 208 workers in Beijing, China. The results support the hypothesis that positive affect serves as a mediator in the relationships between PsyCap and OCBO. Moreover, we also find some support for a reciprocal relationship between PsyCap and positive affect. The theoretical and practical implications of the findings are also discussed

Knowledge, attitudes and practice regarding environmental friendly disinfectants for household use among residents of China in the post-pandemic period

BackgroundA sharp rise in household consumption of disinfectants triggered by COVID-19 pandemic has generated tremendous environmental burden and risks of disinfectant emissions in the post-pandemic period. To address this emerging challenge, replacing highly hazardous disinfectants with more environmental friendly alternatives has been accepted as an inherently effective solution to environment issues posed by disinfectant emerging contaminants. However, no study has yet been done to explore the potential customers' attitudes and the market prospect of environmental friendly disinfectants until now.MethodsThis cross-sectional questionnaire-based survey was conducted from January to March, 2022, among resident volunteers in China, to explore the practices, knowledge and attitudes of the public regarding environmental friendly disinfectants for household use.ResultsAmong a total of 1,861 Chinese residents finally included in the analyses, 18% agreed or strongly agreed that they paid special attention to the environmental certification label on the product, and only bought the environmental certified disinfectant products; 16% and 10% were using environmental friendly disinfectants for hand sanitization and environmental disinfection, respectively. The mean self-assessed and actual knowledge scores were 2.42 ± 1.74 and 2.12 ± 1.97, respectively, out of a total of 5. Participants having good practices of consuming environmental friendly disinfectants achieved higher knowledge scores. Residents' overall attitudes toward the development, consumption and application of environmental friendly disinfectants were very positive. “Possible conflict between disinfection effectiveness and environmental factor of disinfectants in a context of severe COVID-19 pandemic” was considered as the most important barrier jeopardizing the participants' usage intention for environmental friendly disinfectants.ConclusionsThese data suggested most residents of China had a positive attitude, poor knowledge and practices toward environmental friendly disinfectants. More should be done to enhance the residents' environmental knowledge levels about disinfectants, and to further develop and promote disinfectant products with both excellent disinfection activity and environmentally friendly attributes

Spatial Forecast of Landslides in Three Gorges Based On Spatial Data Mining

The Three Gorges is a region with a very high landslide distribution density and a concentrated population. In Three Gorges there are often landslide disasters, and the potential risk of landslides is tremendous. In this paper, focusing on Three Gorges, which has a complicated landform, spatial forecasting of landslides is studied by establishing 20 forecast factors (spectra, texture, vegetation coverage, water level of reservoir, slope structure, engineering rock group, elevation, slope, aspect, etc). China-Brazil Earth Resources Satellite (Cbers) images were adopted based on C4.5 decision tree to mine spatial forecast landslide criteria in Guojiaba Town (Zhigui County) in Three Gorges and based on this knowledge, perform intelligent spatial landslide forecasts for Guojiaba Town. All landslides lie in the dangerous and unstable regions, so the forecast result is good. The method proposed in the paper is compared with seven other methods: IsoData, K-Means, Mahalanobis Distance, Maximum Likelihood, Minimum Distance, Parallelepiped and Information Content Model. The experimental results show that the method proposed in this paper has a high forecast precision, noticeably higher than that of the other seven methods

Highly parallel assays of tissue-specific enhancers in whole Drosophila embryos

Transcriptional enhancers are a primary mechanism by which tissue-specific gene expression is achieved. Despite the importance of these regulatory elements in development, responses to environmental stresses, and disease, testing enhancer activity in animals remains tedious, with a minority of enhancers having been characterized. Here, we have developed ‘enhancer-FACS-Seq’ (eFS) technology for highly parallel identification of active, tissue-specific enhancers in Drosophila embryos. Analysis of enhancers identified by eFS to be active in mesodermal tissues revealed enriched DNA binding site motifs of known and putative, novel mesodermal transcription factors (TFs). Naïve Bayes classifiers using TF binding site motifs accurately predicted mesodermal enhancer activity. Application of eFS to other cell types and organisms should accelerate the cataloging of enhancers and understanding how transcriptional regulation is encoded within them