Biology subjects

Han, Y.

Publications and source records attributed to Han, Y..

338 records · Page 19Linked to original sources

bioRxiv2018

Dominant negative FADD/MORT1 inhibits the development of intestinal intraepithelial lymphocytes with a marked defect on CD8αα+TCRγδ+ T cells

Intestinal intraepithelial lymphocytes are considered to be distinct from thymus-derived cells and are thought to derive locally from cryptopatch (CP) precursors. Although the development and homing of IELs have been studied in some details, the factors controlling their homeostasis are incompletely understood. Here, we demonstrate that FADD, a classic adaptor protein required for death-receptor-induced apoptosis, is a critical regulator of the intestinal IEL development. The mice with a dominant negative mutant of FADD (FADD-DN) display a defective localized intestinal IELs with a marked defect on CD8+TCR{gamma}{delta}+ T cells. Since Lin- LPLs have been identified as precursors CP cells for CD8+ development, we analyzed lamina propria lymphocytes (LPLs) and found the massive accumulation of IL-7R-lin- LPLs in FADD-DN mice. IL-7 plays a differentiation inducing role in the development of intestinal IELs and its receptor IL-7R is a transcriptional target of Notch1. The level of Notch1 expression also showed very low in Lin- LPLs cells from FADD-DN mice compared with normal mice, indicating a possible molecular mechanism of FADD in the early IEL development. In addition, loss of {gamma}{delta} T-IELs induced by FADD-DN results in a worsening inflammation in murine DSS-induced colitis model, suggesting a protective role of FADD in the intestinal homeostasis.

immunology↗

bioRxiv2018

In vivo Chemical Reprogramming of Astrocytes into Functional Neurons

Mammals lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced reprogramming is a spatiotemporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for the in vivo reprogramming in organs with poor regenerative abilities, such as the brain. Here, we demonstrate that in the adult mouse brain, small molecules can reprogram resident astrocytes into functional neurons. The in situ chemically induced neurons (CiNs) resemble endogenous neurons in terms of neuron-specific marker expression and electrophysiological properties. Importantly, these CiNs can integrate into the mouse brain. Our study, for the first time, demonstrates in vivo chemical reprogramming in the adult brain, which could be a novel path for generating desired cells in situ for regenerative medicine.

cell biology↗

bioRxiv2018

Epigenetic Age-Predictor for Mice based on Three CpG Sites

Epigenetic clocks for mice were generated based on deep-sequencing analysis of the methylome. In this study we demonstrate that site-specific analysis of DNA methylation levels by pyrosequencing at only three CG dinucleotides (CpGs) in the genes Prima1, Hsf4, and Kcns1 facilitates precise estimation of chronological age in murine blood samples, too. DBA/2J mice revealed accelerated epigenetic aging as compared to C57BL6 mice, which is in line with their shorter life-expectancy. The three-CpG-predictor provides a simple and cost-effective biomarker to determine biological age in large intervention studies with mice.

genomics↗

bioRxiv2018

A proteome-based design of bitter peptide digestion regime to attenuate cod-bone soup bitterness: comparison with a rainbow trout extract-mediated bitter taste masking approach

BACKGROUNDThe fresh bones (with some meat on them; frequently discarded as a large quantity of industry garbage) of marine fish such as cod and salmon are good materials for manufacture of food additives (taste adjusters). However, such fish-bone originated additives often have apparent bitter taste and need additional debittering regime.\n\nRESULTSIn this study, 46 known bitter peptides in the cod proteome were targeted for specific protease digestion to eliminate bitter taste from the cod bone soup. Though the debittering effect was apparent, the bitter taste was not completely removed. However, the bitter taste can be removed by addition of trout extract to a complete extent. The strong debittering power of rainbow trout extract was further confirmed by the debittering experiments on salmon bone soup and bitter melon, both with perfect results.\n\nCONCLUSIONThese results indicated that the cod bone soup bitterness comes not only from bitter peptide but also from other substances that can be masked by trout extract. Considering the fact that trout proteome has more potential bitter peptides than cod, trout extract shall have a strong bitter masking substance to be determined in the future.

biochemistry↗

bioRxiv2018

The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water

The semi-aquatic bugs conquered water surfaces worldwide and occupy ponds, streams, lakes, mangroves, and even open oceans. As such, they inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders thorough investigations of the mechanisms underlying the processes of adaptation and diversification in this group. Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome, the first water strider genome to be sequenced so far. G. buenoi genome is about 1 000Mb and the sequencing effort recovered 20 949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to water surface lifestyle. These expansions affect key processes such as growth, vision, desiccation resistance, detoxification, olfaction and epigenetic components. Strikingly, the G. buenoi genome contains three Insulin Receptors, a unique case among metazoans, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes include wavelength sensitivity shifts in opsin proteins likely in association with the requirements of vision in water habitats. Our findings suggest that local gene duplications might have had an important role during the evolution of water striders. These findings along with the G. buenoi genome open exciting research opportunities to understand adaptation and genome evolution of this unique hemimetabolous insect.

genomics↗

bioRxiv2017

Ca2+-induced mitochondrial ROS regulate the early embryonic cell cycle

While it has long been appreciated that reactive oxygen species (ROS) can act as second messengers in both homeostastic and stress response signaling pathways, potential roles for ROS during early vertebrate development have remained largely unexplored. Here we show that fertilization in Xenopus embryos triggers a rapid increase in ROS levels, which oscillates with each cell division. Furthermore, we show that the fertilization induced Ca2+ wave is both necessary and sufficient to induce ROS production in activated or fertilized eggs. Using chemical inhibitors, we identified mitochondria as the major source of fertilization induced ROS production. Inhibition of mitochondrial ROS production in early embryos results in cell cycle arrest, in part, via ROS dependent regulation of Cdc25C activity. This study reveals for the first time, a role for oscillating ROS levels in the regulation of the early cell cycle in Xenopus embryos.\n\nHighlightsO_LIROS, including hydrogen peroxide, are produced after fertilization in Xenopus\nC_LIO_LICa2+ signaling after fertilization induces ROS production in mitochondria\nC_LIO_LIMitochondria are the major source of oscillating ROS levels\nC_LIO_LIROS regulate Cdc25C activity and the early cell cycle\nC_LI

developmental biology↗

bioRxiv2017

Elevated and sustained reactive oxygen species levels facilitate mesoderm formation during early Xenopus development

Fertilisation triggers embryonic development culminating with the activation of a number of highly co-ordinated and evolutionarily conserved signalling pathways, which induce and pattern the mesoderm of the developing embryo. Previous studies in invertebrates have shown that hydrogen peroxide (H2O2), a reactive oxygen species (ROS), can act as a signalling molecule for axis specification during early development. Using a HyPer transgenic Xenopus laevis line that expresses a H2O2-sensitive fluorescent protein sensor maternally, we recently found that fertilisation triggers a rapid increase in ROS production. Here we show that this increase in ROS levels is sustained throughout early embryogenesis, lasting until the tailbud stages. In addition we show that lowering ROS levels from the blastula stage through the gastrula stages via antioxidant treatments disrupts mesoderm formation. Furthermore, we show that attenuating ROS levels during the blastula / gastrula stages affects some, but not all, growth factor signalling pathways involved in mesoderm induction and patterning, including the PI3K/Akt, TGF-{beta}/Nodal, and Wnt/{beta}-catenin signalling pathways. These data suggest that sustained elevated ROS levels during the blastula and gastrula stages are essential for early vertebrate embryonic development, at least partly, through their roles in promoting growth factor signalling.

developmental biology↗

bioRxiv2017

Predicting personality traits from resting-state fMRI

Personality neuroscience aims to find associations between brain measures and personality traits. Findings to date have been severely limited by a number of factors, including small sample size and omission of out-of-sample prediction. We capitalized on the recent availability of a large database, together with the emergence of specific criteria for best practices in neuroimaging studies of individual differences. We analyzed resting-state functional magnetic resonance imaging data from 884 young healthy adults in the Human Connectome Project (HCP) database. We attempted to predict personality traits from the \"Big Five\", as assessed with the NEO-FFI test, using individual functional connectivity matrices. After regressing out potential confounds (such as age, sex, handedness and fluid intelligence), we used a cross-validated framework, together with test-retest replication (across two sessions of resting-state fMRI for each subject), to quantify how well the neuroimaging data could predict each of the five personality factors. We tested three different (published) denoising strategies for the fMRI data, two inter-subject alignment and brain parcellation schemes, and three different linear models for prediction. As measurement noise is known to moderate statistical relationships, we performed final prediction analyses using average connectivity across both imaging sessions (1 h of data), with the analysis pipeline that yielded the highest predictability overall. Across all results (test/retest; 3 denoising strategies; 2 alignment schemes; 3 models), Openness to experience emerged as the only reliably predicted personality factor. Using the full hour of resting-state data and the best pipeline, we could predict Openness to experience (NEOFAC_O: r=0.24, R2=0.024) almost as well as we could predict the score on a 24-item intelligence test (PMAT24_A_CR: r=0.26, R2=0.044). Other factors (Extraversion, Neuroticism, Agreeableness and Conscientiousness) yielded weaker predictions across results that were not statistically significant under permutation testing. We also derived two superordinate personality factors (\"\" and \"{beta}\") from a principal components analysis of the NEO-FFI factor scores, thereby reducing noise and enhancing the precision of these measures of personality. We could account for 5% of the variance in the {beta} superordinate factor (r=0.27, R2=0.050), which loads highly on Openness to experience. We conclude with a discussion of the potential for predicting personality from neuroimaging data and make specific recommendations for the field.

neuroscience↗

bioRxiv2017

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the first, 2GB genome of a cockroach, Blattella germanica, and the 1.3GB genome of the drywood termite, Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.

evolutionary biology↗

bioRxiv2017

De novo organelle biogenesis in the cyanobacterium TDX16 released from the green alga Haematococcus pluvialis

It is believed that eukaryotes arise from prokaryotes, which means that organelles can form in the latter. Such events, however, had not been observed previously. Here, we report the biogenesis of organelles in the endosymbiotic cyanobacterium TDX16 that escaped from its senescent/necrotic host cell of green alga Haematococcus pluvialis. In brief, organelle biogenesis in TDX16 initiated with cytoplasm compartmentalization, followed by de-compartmentalization, DNA allocation, and re-compartmentalization, as such two composite organelles-the primitive chloroplast and primitive nucleus sequestering minor and major fractions of cellular DNA respectively were formed. Thereafter, the eukaryotic cytoplasmic matrix was built up from the matrix extruded from the primitive nucleus; mitochondria were assembled in and segregated from the primitive chloroplast, whereby the primitive nucleus and primitive chloroplast matured into nucleus and chloroplast respectively; while most mitochondria turned into double-membraned vacuoles after matrix degradation. Results of pigment analyses, 16S rRNA and genome sequencing revealed that TDX16 is a phycocyanin-containing cyanobacterium resembling Chroococcidiopsis thermalis, which had acquired 9,017,401bp DNAs with 10301 genes form its host. Therefore, organelle biogenesis in TDX16 was achieved by hybridizing the acquired eukaryotic DNAs with its own ones and expressing the hybrid genome.\n\nOrganelle biogenesis in TDX16 results in its transition into a new eukaryotic alga TDX16-DE, which provides a reference to re-understand the development, structure, function and association of organelles in eukaryotes and the reasons behind them, and has implications on other sections of biology, particularly cancer biology and evolutionary biology: (1) the formation and maturation of the small organelle-less nascent cancer cells share striking similarities with TDX16 development and transition, so, it is most likely that cancer cells arise from bacteria; (2) organelle biogenesis in TDX16 uncovers a way of new organelle and new single-celled eukaryote formation, and in light of which, the ancestral organelles were likely formed in rather than transformed form the endosymbiotic prokaryotes that had acquired their hosts DNAs.

cell biology↗

bioRxiv2017

Leukocyte counts based on site-specific DNA methylation analysis

The composition of white blood cells is usually assessed by histomorphological parameters or flow cytometric measurements. Alternatively, leukocyte differential counts (LDCs) can be estimated by deconvolution algorithms for genome-wide DNA methylation (DNAm) profiles. We identified cell-type specific CG dinucleotides (CpGs) that facilitate relative quantification of leukocyte subsets. Site-specific analysis of DNAm levels by pyrosequencing provides similar precision of LDCs as conventional methods, whereas it is also applicable to frozen samples and requires only very small volumes of blood. Furthermore, we describe a new approach for absolute quantification of cell numbers based on a non-methylated reference DNA. Our \"Epi-Blood-Count\" facilitates robust and cost effective analysis of blood counts for clinical application.

molecular biology↗

bioRxiv2017

A single-cell anatomical blueprint for intracortical information transfer from primary visual cortex

The wiring diagram of the neocortex determines how information is processed across dozens of cortical areas. Each area communicates with multiple others via extensive long-range axonal projections 1-6, but the logic of inter-area information transfer is unresolved. Specifically, the extent to which individual neurons send dedicated projections to single cortical targets or distribute their signals across multiple areas remains unclear5,7-20. Distinguishing between these possibilities has been challenging because axonal projections of only a few individual neurons have been reconstructed. Here we map the projection patterns of axonal arbors from 591 individual neurons in mouse primary visual cortex (V1) using two complementary methods: whole-brain fluorescence-based axonal tracing21,22 and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq)23. Although our results confirm the existence of dedicated projections to certain cortical areas, we find these are the exception, and that the majority of V1 neurons broadcast information to multiple cortical targets. Furthermore, broadcasting cells do not project to all targets randomly, but rather comprise subpopulations that either avoid or preferentially innervate specific subsets of cortical areas. Our data argue against a model of dedicated lines of intracortical information transfer via \"one neuron - one target area\" mapping. Instead, long-range communication between a sensory cortical area and its targets may be based on a principle whereby individual neurons copy information to, and potentially coordinate activity across, specific subsets of cortical areas.

neuroscience↗

bioRxiv2017

Releasing potential power of terpene synthases by a robust precursor supply platform

Approximately 76,000 discovered makes terpenoids the largest family of natural products in nature with widespread applications. The wide-spectrum of structural diversity of the terpenoids were largely due to the variable skeletons generated by terpene synthases. The number of terpene skeletons found in nature, however, were so much more than those conceivably generated from known terpene synthases and the limited characterized terpene synthases also make no chance for some useful terpenoids overproduction in microbe. Here, we first demonstrated that the promiscuous synthases in vivo can produce more variable terpenoid products by converting precursors of different lengths (C10, C15, C20, C25). This discovery was prompted by the development of an efficient in vivo platform by combining the two promiscuous terpene synthases and three prenyltransferases to generate 50 terpenoids, at least 3 ring systems of which were completely new. Furthermore, protein engineering was further integrated to enhance product diversity. Clearly, the work is expected to dramatically reshape the terpenoid research by widening the flexibility of the terpene synthases for the fresh discovery or creation of the new terpenoid compounds by skeleton reframing.

biochemistry↗

bioRxiv2017

The house spider genome reveals an ancient whole-genome duplication during arachnid evolution

The duplication of genes can occur through various mechanisms and is thought to make a major contribution to the evolutionary diversification of organisms. There is increasing evidence for a large-scale duplication of genes in some chelicerate lineages including two rounds of whole genome duplication (WGD) in horseshoe crabs. To investigate this further we sequenced and analyzed the genome of the common house spider Parasteatoda tepidariorum. We found pervasive duplication of both coding and non-coding genes in this spider, including two clusters of Hox genes. Analysis of synteny conservation across the P. tepidariorum genome suggests that there has been an ancient WGD in spiders. Comparison with the genomes of other chelicerates, including that of the newly sequenced bark scorpion Centruroides sculpturatus, suggests that this event occurred in the common ancestor of spiders and scorpions and is probably independent of the WGDs in horseshoe crabs. Furthermore, characterization of the sequence and expression of the Hox paralogs in P. tepidariorum suggests that many have been subject to neofunctionalization and/or subfunctionalization since their duplication, and therefore may have contributed to the diversification of spiders and other pulmonate arachnids.

genomics↗