Biology subjects

Song, Y.

Publications and source records attributed to Song, Y..

At least 361 records · Page 20Linked to original sources

bioRxiv2020

Characterizing Sleep-Wake Circadian Rhythm Consolidation in Early Childhood and Its Association with Motor Development Using Actigraphy

BackgroundWearable devices have been widely used in clinical studies to study daily activity patterns, but the analysis remains the major obstacle for researchers. Study ObjectiveThis study proposed a novel method to characterize sleep-activity rhythms using actigraphy and further used it to describe early childhood daily rhythm formation and examine its association with physical development. MethodsWe developed a machine learning-based Penalized Multi-band Learning (PML) algorithm to sequentially infer dominant periodicities based on Fast Fourier Transform (FFT) and further characterize daily rhythms. We implemented and applied the algorithm to Actiwatch data collected from a 262 healthy infant cohort at 6-, 12-, 18-, and 24-month old, with 159, 101, 111, and 141 subjects participating at each time point respectively. Autocorrelation analysis and Fishers test for harmonic analysis with Bonferroni correction were applied to compare with PML. The association between activity rhythm features and early childhood motor development, assessed by Peabody Developmental Motor Scales-Second Edition (PDMS-2), was studied through linear regression. ResultsPML results showed that 1-day periodicity is most dominant at 6 and 12 months, whereas 1-day, 1/3-day, and 1/2-day periodicities are most dominant at 18 and 24 months. These periodicities are all significant in Fishers test, with 1/4-day periodicity also significant at 12 months. Autocorrelation effectively detected 1-day periodicity but not others. At 6 months, PDMS-2 is associated with assessment seasons. At 12 months, PDMS-2 is associated with seasons and FFT signals at 1/3-day periodicity (P<.001) and 1/2-day periodicity (P=.04). In particular, subcategories of stationary, locomotion, and gross motor are associated with FFT signals at 1/3-day periodicity (P<.001). ConclusionsThe proposed PML algorithm can effectively conduct circadian rhythm analysis using time-series wearable device data. Application of the method effectively characterized sleep-wake rhythm development and identified the association between daily rhythm formation and motor development during early childhood.

neuroscience↗

bioRxiv2020

The combination of lipopolysaccharide and D-galactosamine administration show positive genotoxic effect in mice liver

Lipopolysaccharide (LPS)/D-galactosamine (D-GalN) co-administration induced acute liver injury (ALI) and hepatic fibrosis have been extensively studied. However, whether LPS/D-GalN show genotoxic effect is current unknown. Male mice were divided into eight groups and each group contain eight animals. For the acute administration of LPS/D-GalN, the mice were given a single intraperitoneal (i.p.) injection of LPS/D-GalN (25 g/kg + 250 mg/kg, 25 g/kg + 500 mg/kg, 50 g/kg + 500 mg/kg body weight) for 6 h, respectively. The chronic administration was conduct by the i.p. injection of LPS/D-GalN (10 g/kg + 100 mg/kg) every other day for 8 weeks. Saline solution (0.9%) and cyclophosphamide (CTX) (50 mg/kg body weight) injection were used as negative and positive control, respectively. Using single cell gel electrophoresis (SCGE) assay, we found that the acute administration of LPS/D-GalN induces severe DNA damage in mice hepatic cells, but not in brain, sperm and bone marrow cells, implied the genotoxicity of LPS/D-GalN. Interestingly, the chronic treatment of LPS/D-GalN causes significant genotoxic effect in both hepatic and brain cells, but not sperm and bone marrow cells. Histopathological examination in liver and brain section consistent with SCGE results, accordingly. Our study, for the first time, reported the genotoxic potential of LPS/D-GalN co-administration. In addition, LPS/D-GalN administration may serve as an experimental model for further genotoxic study.

cell biology↗

bioRxiv2020

Rice NIN-LIKE PROTEIN 4 is a master regulator of nitrogen use efficiency

Nitrogen (N) is one of the key essential macronutrients that affects rice growth and yield. Inorganic N fertilizers are excessively used to boost yield and generate serious collateral environmental pollution. Therefore, improving crop N use efficiency (NUE) is highly desirable and has been a major endeavor in crop improvement. However, only a few regulators have been identified that can be used to improve NUE in rice to date. Here we show that the NIN-like protein OsNLP4 significantly improves the rice NUE and yield. Field trials consistently showed that loss-of-OsNLP4 dramatically reduced yield and NUE compared with wild type under different N regimes. In contrast, the OsNLP4 overexpression lines remarkably increased yield by 30% and NUE by 47% under moderate N level compared with wild type. Transcriptomic analyses revealed that OsNLP4 orchestrates the expression of a majority of known N uptake, assimilation and signaling genes by directly binding to the nitrate-responsive cis-element in their promoters to regulate their expression. Moreover, overexpression of OsNLP4 can recover the phenotype of Arabidopsis nlp7 mutant and enhance its biomass. Our results demonstrate that OsNLP4 is a master regulator of NUE in rice and sheds light on crop NUE improvement.

plant biology↗

bioRxiv2020

Complete genome and phylogenetic analysis of bovine papillomavirus type 15 in Southern Xinjiang dairy cow

In this study, the complete genome sequence of bovine papillomavirus (BPV) type 15 (BPV Aks-02), a novel putative BPV type from a skin sample of a cow in southern Xinjiang, China was determined by collecting cutaneous neoplastic lesion, followed by DNA extraction and amplicon sequencing. The complete genome consisted of 7189 base pairs (G+C content of 42.50%) that encoded five early (E8, E7, E1, E2, E4) and two late (L1 and L2) genes. The E7 protein contained a consensus CX2CX29CX2C zinc-binding domain and an LxCxE motif. The nucleotide sequence of the L1 open reading frame (ORF) was related mostly (99%) to the L1 ORF of putative type BAPV-3 reference strain from GenBank. Phylogenetic analysis and sequence similarities based on the L1 ORF suggest that BPV type (BPV Aks-02) clustered with members of genus Xipapillomavirus as BPV15, and closely related to Xipapillomavirus 1.

microbiology↗

bioRxiv2019

Optical activation of TrkB receptors

Brain-derived neurotrophic factor (BDNF), via activation of tropomyosin receptor kinase B (TrkB), plays a critical role in neuronal proliferation, differentiation, survival, and death. Dysregulation of TrkB signaling is implicated in neurodegenerative disorders and cancers. Precise activation of TrkB receptors with spatial and temporal resolution is greatly desired to study the dynamic nature of TrkB signaling and its role in related diseases. Here we develop different optogenetic approaches that use light to activate TrkB receptors. Utilizing the photosensitive protein Arabidopsis thaliana cryptochrome 2 (CRY2), the light-inducible homo-interaction of the intracellular domain of TrkB (iTrkB) in the cytosol or on the plasma membrane is able to induce the activation of downstream MAPK/ERK and PI3K/Akt signaling as well as the neurite outgrowth of PC12 cells. Moreover, we prove that such strategies are generalizable to other optical homo-dimerizers by demonstrating the optical TrkB activation based on the light-oxygen-voltage domain of aureochrome 1 from Vaucheria frigida. The results open up new possibilities of many other optical platforms to activate TrkB receptors to fulfill customized needs. By comparing all the different strategies, we find that the CRY2-integrated approach to achieve light-induced cell membrane recruitment and homo-interaction of iTrkB is most efficient in activating TrkB receptors. The optogenetic strategies presented are promising tools to investigate BDNF/TrkB signaling with tight spatial and temporal control.

synthetic biology↗

bioRxiv2019

Millet-based supplement restored microbiota diversity of acute undernourished pigs

The strong connection between undernutrition and gut microbiota (GM) has enabled microbiota-targeting to become an evolving strategy, which witnessed urgent need for fortified formula of supplementary food in undernutrition therapy. Using undernourished pigs as models, we investigated how corn- and millet-based nutritional supplement acted differently in modulating microbiota. Undernourished pigs at age of 9 weeks were fed with pure maize diet (Maize), corn-based (CSB+) and millet-based (MSB+) supplementary food for 3 weeks. Compared with Maize group, both CSB+ and MSB+ improved serum total protein and globulin level, but no physiological improvement was observed by short-term food intervention. MSB+ shown superior influence on GM immaturity which were more normally-grown like at both structural and functional level. Higher level of Bacteriodetes, Firmicutes and lower level of Preteobacteria were detected in MSB+ fed piglets in contrast with CSB+. Lachnospira.spp was significantly raised after nutritional intervention, indicating high correlation with the undernutrition-associated phenotype. Thus, especially from the GM aspect, millet could be one promising source to help undernourished children reconstruct balanced microbiota in short therapeutic term.

microbiology↗

bioRxiv2019

Identification of Genomic Insertion and Flanking Sequences of the Transgenic Drought-tolerant Maize Line "SbSNAC1-382" using the Single Molecular Real-Time (SMRT) Sequencing Method

Safety assessment of genetically modified (GM) crops is crucial in the phase of product development before the GM crops are put on the market. Characteristics of flanking sequences of exogenous insertion sequences are essential for the safety assessment and marking of transgenic crops. In this study, we used the methods of genome walking and whole genome sequencing (WGS) to identify the flanking sequence characteristics of a SbSNAC1 transgenic drought-tolerant maize line "SbSNAC1-382", but both of the methods failed. Then, we constructed a genomic fosmid library of the transgenic maize line, which contained 4.18x105 clones with an average insertion fragment of 35 kb, covering 5.85 times of the maize genome. Subsequently, three positive clones were screened by pairs of specific primers and one of the three positive clones was sequenced by using the Single Molecule Real-Time (SMRT) sequencing technology. More than 1.95 Gb sequence data ([~]105 x coverage) for the sequenced clone was generated. The junction reads mapped to the boundaries of T-DNA and the flanking sequences in the transgenic line were identified by comparing all sequencing reads with the maize reference genome and the sequence of transgenic vector. Furthermore, the putative insertion loci and flanking sequences were confirmed by PCR amplification and Sanger sequencing. The results indicated that two copies of the exogenous T-DNA fragments were inserted in the same genomic site. And the exogenous T-DNA fragments were integrated at the position of Chromosome 5: 177155650 to 177155696 in the transgenic line 382. Herein, we have demonstrated the successful application of the SMRT technology for the characterization of genomic insertion and flanking sequences.

molecular biology↗

bioRxiv2019

Genomic Characterization of SiGRFs in Foxtail Millet and SiGRF1-overexpression in Arabidopsis thaliana Promotes Plant Avoidance of Salt Stress

In plants, 14-3-3 proteins are recognized as mediators of signal transduction and function in both development and stress response. However, their functions have not been reported in the C4 crop foxtail millet. Here, phylogenetic analysis categorized foxtail millet 14-3-3s (SiGRFs) into ten discrete groups (Clusters I to {square}). Transcriptome and qPCR analyses showed that all the SiGRFs responded to at least one abiotic stress. All but one SiGRF-overexpressing (OE) Arabidopsis thaliana line (SiGRF1) exhibited insensitivity to abiotic stresses during seed germination and seedling growth. Compared with the Col-0 wild-type, SiGRF1-OEs had slightly lower germination rates and smaller leaves. However, flowering time of SiGRF1-OEs occurred earlier than that of Col-0 under high-salt stress. Interaction of SiGRF1 with a foxtail millet E3 ubiquitin-protein ligase (SiRNF1/2) indicates that the proteinase system might hydrolyse SiGRF1. Further investigation showed that SiGRF1 localized in the cytoplasm, and its gene was ubiquitously expressed in various tissues throughout various developmental stages. Additionally, flowering-related genes, WRKY71, FLOWERING LOCUS T, LEAFY and FRUITFULL, in SiGRF1-OEs exhibited considerably higher expression levels than those in Col-0 under salinity-stressed conditions. Results suggest that SiGRF1 hastens flowering, thereby providing a means for foxtail millet to complete its life cycle and avoid further salt stress. HighlightSiGRFs in foxtail millet: SiGRF1 hastens flowering in transgenic Arabidopsis thaliana exposed to salt stress

genomics↗

bioRxiv2019

Existence and functions of hypothalamic kisspeptin neuropeptide signaling system in a non-chordate deuterostome species

The kisspeptin (Kp) system is a central modulator of the hypothalamic-pituitary-gonadal axis in vertebrates. Its existence outside the vertebrate lineage remains largely unknown. Here we report the identification and characterization of Kp system in the sea cucumber Apostichopus japonicus. The gene encoding the Kp precursor, generates two mature neuropeptides, AjKiss1a and AjKiss1b. The Kp receptors, AjKissR1 and AjKissR2, are strongly activated by synthetic A. japonicus and vertebrate Kps, triggering a rapid intracellular mobilization of Ca2+, followed by receptor internalization. AjKissR1 and AjKissR2 share similar intracellular signaling pathways via Gq/PLC/PKC/MAPK cascade, when activated by C-terminal decapeptide (AjKiss1b-10). The A. japonicus Kp system functions in mutiple tissues which are closely related to reproduction and metabolism. Overall, our findings uncover for the first time, to our knowledge, the existence and function of the Kp system in a non-chordate species and provide new evidence to support the ancient origin of the hypothalamic neurosecretory system.

evolutionary biology↗

bioRxiv2019

Predictive Coding Models for Pain Perception

Pain is a complex, multidimensional experience that involves dynamic interactions between sensory-discriminative and affective-emotional processes. Pain experiences have a high degree of variability depending on their context and prior anticipation. Viewing pain perception as a perceptual inference problem, we propose a predictive coding paradigm to characterize evoked and non-evoked pain. We record the local field potentials (LFPs) from the primary somatosensory cortex (S1) and the anterior cingulate cortex (ACC) of freely behaving rats--two regions known to encode the sensory-discriminative and affective-emotional aspects of pain, respectively. We further use predictive coding to investigate the temporal coordination of oscillatory activity between the S1 and ACC. Specifically, we develop a phenomenological predictive coding model to describe the macroscopic dynamics of bottom-up and top-down activity. Supported by recent experimental data, we also develop a biophysical neural mass model to describe the mesoscopic neural dynamics in the S1 and ACC populations, in both naive and chronic pain-treated animals. Our proposed predictive coding models not only replicate important experimental findings, but also provide new prediction about the impact of the model parameters on the physiological or behavioral read-out--thereby yielding mechanistic insight into the uncertainty of expectation, placebo or nocebo effect, and chronic pain.

neuroscience↗

bioRxiv2019

Patterned Neuronal Activities Dictate Cell Type-specific Axon Regeneration

Why closely related neuronal types differ in their axon regenerative abilities remains elusive. Here, we demonstrate gliotransmission determines such a difference in Drosophila larval sensory neurons. Axotomy activates ensheathing glia, which signal to regenerative neurons through the gliotransmitter adenosine, to mount regenerative programs including neuronal activity and Ras. Surprisingly, ensheathing glia do not signal to non-regenerative neurons. Such neuronal type-specific responses to gliotransmission result from specific expression of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes regeneration of regenerative neurons. Strikingly, reconstitution of gliotransmission in non-regenerative neurons enables them to regenerate. Furthermore, activation of an adenosine receptor ortholog in adult mice promotes both regeneration and survival of retinal ganglion cells, uncovering a conserved pro-regenerative role of adenosine receptors. Our studies demonstrate gliotransmission as a novel mechanism by which glia instruct axon regeneration, with neuronal type-specificity, and suggest targeting purinergic signaling as a new strategy for mammalian central nervous system repair. HIGHLIGHTSEnsheathing glia differentially interact with Drosophila sensory neuron types through gliotransmission Gliotransmission mounts axon regenerative programs in selective neuronal types Neuronal firing pattern but not overall excitability dictates axon regeneration outcome Adenosine receptor activation in adult mice promotes both regeneration and survival of RGCs

neuroscience↗

bioRxiv2019

Initial data release and announcement of the Fish10K: Fish 10,000 Genomes Project

With more than 30,000 species, fish are the largest and most ancient vertebrate group. Despite their critical roles in many ecosystems and human society, fish genomics lags behind work on birds and mammals. This severely limits our understanding of evolution and hinders progress on the conservation and sustainable utilization of fish. Here, we announce the Fish10K project, an international collaborative project or initiative? aiming to sequence 10,000 representative fish genomes under a systematic context within ten years, and officially welcome collaborators to join this effort. As a step towards this goal, we herein describe a feasible workflow for the procurement and storage of biospecimens, and sequencing and assembly strategies. To illustrate, we present the genomes of ten fish species from a cohort of 93 species chosen for technology development.

genomics↗

bioRxiv2019

Non-parallel transcriptional divergence during parallel adaptation

How underlying mechanisms bias evolution toward predictable outcomes remains an area of active debate. In this study, we leveraged phenotypic plasticity and parallel adaptation across independent lineages of Trinidadian guppies (Poecilia reticulata) to assess the predictability of gene expression evolution during parallel adaptation. Trinidadian guppies have repeatedly and independently adapted to high- and low-predation environments in the wild. We combined this natural experiment with a laboratory breeding design to attribute transcriptional variation to the genetic influences of population of origin and developmental plasticity in response to rearing with or without predators. We observed substantial gene expression plasticity as well as the evolution of expression plasticity itself across populations. Genes exhibiting expression plasticity within populations were more likely to also differ in expression between populations, with the direction of population differences more likely to be opposite those of plasticity. While we found more overlap than expected by chance in genes differentially expressed between high- and low-predation populations from distinct evolutionary lineages, the majority of differentially expressed genes were not shared between lineages. Our data suggest alternative transcriptional configurations associated with shared phenotypes, highlighting a role for transcriptional flexibility in the parallel phenotypic evolution of a species known for rapid adaptation.

evolutionary biology↗

bioRxiv2019

Miswired enhancer logic drives translocation positive rhabdomyosarcoma

Core regularity transcription factors (CR TFs) define cell identity and lineage through an exquisitely precise and logical order during embryogenesis and development. These CR TFs regulate one another in three-dimensional space via distal enhancers that serve as logic gates embedded in their TF recognition sequences. Aberrant chromatin organization resulting in miswired circuitry of enhancer logic is a newly recognized feature in many cancers. Here, we report that PAX3-FOXO1 expression is driven by a translocated FOXO1 distal super enhancer (SE). Using 4C-seq, a technique detecting all genomic regions that interact with the translocated FOXO1 SE, we demonstrate its physical interaction with the PAX3 promotor only in the presence of the oncogenic translocation. Furthermore, RNA-seq and ChIP-seq in tumors bearing rare PAX translocations implicate enhancer miswiring is a pervasive feature across all FP-RMS tumors. HiChIP of enhancer mark H3K27ac showed extended connectivity between the distal FOXO1 SE and additional intra-domain enhancers and the PAX3 promoter. We show by CRISPR-paired-ChIP-Rx that PAX3-FOXO1 transcription is diminished when this network of enhancers is selectively ablated. Therefore, our data reveal a mechanism of a translocated hijacked enhancer which disrupts the normal CR TF logic during skeletal muscle development (PAX3 to MYOD to MYOG), replacing it with an infinite loop logic that locks rhabdomyosarcoma cells in an undifferentiated proliferating stage.

cancer biology↗

bioRxiv2019

Stromal ISLR promotes intestinal regeneration and cancer by suppressing epithelial Hippo signaling

The YAP signaling activation in epithelial cells is essential for intestinal regeneration and tumorigenesis. However, the molecular mechanism linking stromal signals to YAP-mediated intestinal regeneration and tumorigenesis is poorly defined. Here we report a stroma-epithelia YAP signaling axis essential for stromal cells to modulate epithelial cell growth during intestinal regeneration and tumorigenesis. Specifically, upon inflammation and in cancer, an oncogenic transcription factor ETS1 in stromal cells induces expression of a secreted protein ISLR that can directly binds to a transmembrane protocadherin FAT1 on the surface of epithelial cells. This binding suppressed the Hippo signaling by disrupting MST1-FAT1 association, resulting in YAP signaling activation. Deletion of Islr in stromal cells in mice markedly impaired intestinal regeneration, and suppressed tumorigenesis in the colon. Moreover, the expression of stromal cell-specific ISLR and ETS1 significantly increased in inflamed mucosa of human IBD patients and in human colorectal adenocarcinoma, accounting for the epithelial YAP hyperactivation. Collectively, our findings uncovered a molecular mechanism governing signals for communication between stroma and epithelium during tissue regeneration and tumorigenesis.

cancer biology↗

bioRxiv2019

Saccadic adaptation in the presence of artificial central scotomas

Saccadic adaptation can occur over a short period of time through a constant adjustment of the saccade target during the saccade, resulting in saccadic re-referencing which directs the saccade to a location different from the target that elicited the saccade. Saccade re-referencing could be used to help patients with age-related macular degeneration (AMD) to optimally use their residual visual function. However, it remains unknown whether saccade adaptation can take place in the presence of central scotomas (i.e., without central vision). We tested participants in two experiments in a conventional double-step paradigm with a central gaze-contingent artificial scotoma. Experiment 1 (N = 12) comprised a backward adaptation paradigm with a visible and an invisible 3{degrees} diameter scotomas. Experiment 2 (N = 13) comprised a forward adaptation paradigm with invisible 2{degrees} and 4{degrees} diameter scotomas. In Experiment 1, we observed significant adaptation in both the visible and invisible scotoma conditions comparable to the control condition with no scotoma. This was the case even when the saccade landed such that the target was occluded by the scotoma. We observed that adaptation occurred based on peripheral viewing of the stepped target during the deceleration period. In Experiment 2, we found that both scotoma conditions showed adaptation again comparable to the control condition with no scotoma. We conclude that saccadic adaptation can occur with central scotomas, showing that it does not require central vision and is driven primarily by peripheral retinal error.

neuroscience↗

bioRxiv2019

Chromosome-level genome assembly of a butterflyfish, Chelmon rostratus

Chelmon rostratus (Teleostei, Perciformes, Chaetodontidae) is a copperband butterflyfish. As an ornamental fish, the genome information for this species might help understanding the genome evolution of Chaetodontidae and adaptation/evolution of coral reef fish.\n\nIn this study, using the stLFR co-Barcode reads data, we assembled a genome of 638.70 Mb in size with contig and scaffold N50 sizes of 294.41 kb and 2.61 Mb, respectively. 94.40% of scaffold sequences were assigned to 24 chromosomes using Hi-C data and BUSCO analysis showed that 97.3% (2,579) of core genes were found in our assembly. Up to 21.47 % of the genome was found to be repetitive sequences and 21,375 protein-coding genes were annotated. Among these annotated protein-coding genes, 20,163 (94.33%) proteins were assigned with possible functions.\n\nAs the first genome for Chaetodontidae family, the information of these data helpfully to improve the essential to the further understanding and exploration of marine ecological environment symbiosis with coral and the genomic innovations and molecular mechanisms contributing to its unique morphology and physiological features.

genomics↗

bioRxiv2019

Inhibiting Mycobacterium tuberculosis ClpP1P2 by addressing the equatorial handle domain of ClpP1 subunit

Unlike other bacterial ClpP systems, mycobacterial ClpP1P2 complex is essential for mycobacterial survival. The functional details of Mycobacterium tuberculosis (Mtb) ClpP1P2 remains largely elusive and selectively targeting ClpP of different species is a big challenge. In this work, cediranib was demonstrated to significantly decrease the activity of MtbClpP1P2. By solving the crystal structure of cediranib-bound MtbClpP1P2, we found that cediranib dysregulates MtbClpP1P2 by interfering with handle domain of the equatorial region of MtbClpP1, indicating that the inter-ring dynamics are crucial for its function. This finding provides direct evidence for the notion that a conformational switch in the equatorial handle domain is essential for ClpP activity. We also present biochemical data to interpret the distinct interaction pattern and inhibitory properties of cediranib toward MtbClpP1P2. These results suggest that the variable handle domain region is responsible for the species-selectivity of cediranib, which suggests the equatorial handle domain as a potential region for screening pathogen-specific ClpP inhibitors.

biochemistry↗