Biology subjects

Gu, J.

Publications and source records attributed to Gu, J..

8 recordsLinked to original sources

bioRxiv2018

KRAB Zinc Finger Proteins coordinate across evolutionary time scales to battle retroelements

KRAB Zinc Finger Proteins (KZNFs) are the largest and fastest evolving family of human transcription factors1,2. The evolution of this protein family is closely linked to the tempo of retrotransposable element (RTE) invasions, with specific KZNF family members demonstrated to transcriptionally repress specific families of RTEs3,4. The competing selective pressures between RTEs and the KZNFs results in evolutionary arms races whereby KZNFs evolve to recognize RTEs, while RTEs evolve to escape KZNF recognition5. Evolutionary analyses of the primate-specific RTE family L1PA and two of its KZNF binders, ZNF93 and ZNF649, reveal specific nucleotide and amino changes consistent with an arms race scenario. Our results suggest a model whereby ZNF649 and ZNF93 worked together to target independent motifs within the L1PA RTE lineage. L1PA elements eventually escaped the concerted action of this KZNF \"team\" over [~]30 million years through two distinct mechanisms: a slow accumulation of point mutations in the ZNF649 binding site and a rapid, massive deletion of the entire ZNF93 binding site.

evolutionary biology↗

bioRxiv2018

PARylation modulates stress granule assembly, phase separation, and neurotoxicity of ALS-related RNA-binding proteins

Mutations in RNA-binding proteins localized in ribonucleoprotein (RNP) granules, such as hnRNP A1 and TDP-43, promote aberrant protein aggregations, which are pathological hallmarks in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Protein posttranslational modifications (PTMs) are known to regulate RNP granules. In this study, we investigate the function of PARylation, an important PTM involved in DNA damage repair and cell death, in RNP-related neurodegeneration. We reveal that PARylation levels are a major regulator of the dynamic assembly-disassembly of RNP granules, and the disease-related RNPs such as hnRNP A1 and TDP-43 can both be PARylated and bind to PARylated proteins. We further identify the PARylation site of hnRNP A1 at K298, which controls the cytoplasmic translocation of hnRNP A1 in response to stress, as well as the PAR-binding motif (PBM) of hnRNP A1, which is required for the delivery and association of hnRNP A1 to stress granules. Moreover, we show that PAR not only dramatically enhances the liquid-liquid phase separation of hnRNP A1, but also promotes the co-phase separation of hnRNP A1 and TDP-43 in vitro and their interaction in vivo. Finally, we establish that both genetic and pharmacological inhibition of PARP mitigates hnRNP A1 and TDP-43-mediated neurotoxicity in cell and Drosophila models of ALS. Together, our findings indicate a novel and crucial role of PARylation in regulating the assembly and the dynamics of RNP granules, and dysregulation of PARylation may contribute to ALS disease pathogenesis.

neuroscience↗

bioRxiv2018

Categorized analysis of forest ecological values in the China’s conversion cropland to forest program

Background\n\nThe Chinas Conversion Cropland to Forest Program (CCFP) is one of the large state ecological construction programs. Up to now, the program has effectively improved the ecological environment and produced large ecological benefit. However, there were also some problems in its implementation process, the program has been sometimes less effective than the expected.\n\nMethods\n\nBased on the data and the methods of State report on monitoring ecological effects in CCFP and the Chinese Forest Ecosystem Research Network (CFERN) in 2013, we analyzed the categorized forest ecological benefit value (B-V) s in the three forest restoration ways in different regions in China to provide references for CCFP construction.\n\nResults\n\nThe unit area B-Vs in CCFP varied between 35 000 RMBs.hm-2.a-1 and 100 000 RMBs.hm-2.a-1. Water conservation B-V and species conservation B-V were the two largest constituents, nutrient accumulation B-V was the least in all the categorized B-Vs on regional and unit area scale. The rank of restoration ways on average unit area total B-Vs was-- hillside forest conservation > returning cropland to forest > afforestation on suitable barren hills and wasteland in CCFP. Among the categorized B-Vs, some pairs were positively correlated with each other and some were negatively correlative. The correlation coefficients and some regression equations were given in the text and the attached Fig.s.\n\nConclusions\n\nWater conservation B-V was the highest and nutrient accumulation B-V was the lowest whether on regional or unit area scale in CCFP.\n\nForest ecological B-Vs varied in different forest restoration ways and different regions in CCFP. The hillside forest conservation restoration way and the water conservation B-V should be paid more attention in Chinas future forest restoration. We suggest that suitable forest restoration ways should be selective according to the regional specific and ecological targets.\n\nThere were correlations among the categorized B-Vs, and the correlations varied with different forest restoration ways in CCFP. Knowing about the correlations could clarify the targeted restoration ways according to the goal of ecological benefit.

ecology↗

bioRxiv2018

A high-quality, long-read de novo genome assembly to aid conservation of Hawaii’s last remaining crow species

Genome-level data can provide researchers with unprecedented precision to examine the causes and genetic consequences of population declines, and to apply these results to conservation management. Here we present a high-quality, long-read, de novo genome assembly for one of the worlds most endangered bird species, the Alala. As the only remaining native crow species in Hawaii, the Alala survived solely in a captive breeding program from 2002 until 2016, at which point a long-term reintroduction program was initiated. The high-quality genome assembly was generated to lay the foundation for both comparative genomics studies, and the development of population-level genomic tools that will aid conservation and recovery efforts. We illustrate how the quality of this assembly places it amongst the very best avian genomes assembled to date, comparable to intensively studied model systems. We describe the genome architecture in terms of repetitive elements and runs of homozygosity, and we show that compared with more outbred species, the Alala genome is substantially more homozygous. We also provide annotations for a subset of immunity genes that are likely to be important for conservation applications, and we discuss how this genome is currently being used as a roadmap for downstream conservation applications.

genomics↗

bioRxiv2018

TRAF6 directs Foxp3 localization and facilitates Treg function through K63-type ubiquitination

Regulatory T cells (Treg) are crucial mediators of immune control. The characteristic gene expression and suppressive function of Treg depend considerably on the stable expression and activity of the transcription factor Foxp3. While transcriptional regulation of the Foxp3 gene has been studied in depth, both the expression and function of Foxp3 are also modulated at the protein level. However, the molecular players involved in posttranslational Foxp3 regulation are just beginning to be elucidated. Here we found TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to B16 melanomas and displayed enhanced anti-tumor immunity. We further determined that Foxp3 undergoes lysine-63 chain (K63) ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. When deprived of TRAF6 activity or rendered insensitive to K63 ubiquitination, Foxp3 displayed aberrant, perinuclear accumulation, disrupted function. Thus, Foxp3 ubiquitination by TRAF6 ensures proper localization of Foxp3 and facilitates Foxp3s gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing force that may be targeted in novel tolerance-breaking therapies.

immunology↗

bioRxiv2018

The action of a cosmetic hair treatment on follicle function

OBJECTIVEHuman hair changes with age: fibre diameter and density decrease, hair growth slows and shedding increases. This series of controlled studies examined the effect on hair growth parameters of a new leave-on hair treatment (LOT) formulated with DynagenTM (containing hydrolysed yeast protein) and zinc salts.\n\nMETHODSHair growth data were collected from healthy women aged 18-65 years. The LOTs effect on hair growth was measured in a randomized double-blind study and in hair samples; its effect on follicle-cell proliferation was assessed by quantifying Ki67 expression in scalp biopsies. The LOTs effect on plucking force was determined in an ex vivo model. Dynagens effect on the expression of the tight-junction marker claudin-1 was analysed in cultured follicles. The effect on protease activity of zinc salts used in the LOT was examined in vitro.\n\nRESULTSHair growth rate decreased with increasing subject age. The LOT significantly increased hair growth rate, fibre diameter, bundle cross-sectional area, Ki67 expression and the plucking force required to remove hair. Dynagen significantly increased claudin-1 expression in cultured follicles. Protease activity was reduced by zinc salts.\n\nCONCLUSIONThe Dynagen-based LOT increases hair-fibre diameter, strengthens the follicular root structure and increases hair growth rate.

physiology↗

bioRxiv2018

fastp: an ultra-fast all-in-one FASTQ preprocessor

MotivationQuality control and preprocessing of FASTQ files are essential to providing clean data for downstream analysis. Traditionally, a different tool is used for each operation, such as quality control, adapter trimming, and quality filtering. These tools are often insufficiently fast as most are developed using high-level programming languages (e.g., Python and Java) and provide limited multi-threading support. Reading and loading data multiple times also renders preprocessing slow and I/O inefficient.\n\nResultsWe developed fastp as an ultra-fast FASTQ preprocessor with useful quality control and data-filtering features. It can perform quality control, adapter trimming, quality filtering, per-read quality cutting, and many other operations with a single scan of the FASTQ data. It also supports unique molecular identifier preprocessing, poly tail trimming, output splitting, and base correction for paired-end data. It can automatically detect adapters for single-end and paired-end FASTQ data. This tool is developed in C++ and has multi-threading support. Based on our evaluation, fastp is 2-5 times faster than other FASTQ preprocessing tools such as Trimmomatic or Cutadapt despite performing far more operations than similar tools.\n\nAvailability and ImplementationThe open-source code and corresponding instructions are available at https://github.com/OpenGene/fastp\n\nContactchen@haplox.com

bioinformatics↗

bioRxiv2017

VASC: dimension reduction and visualization of single cell RNA sequencing data by deep variational autoencoder

Single cell RNA sequencing (scRNA-seq) is a powerful technique to analyze the transcriptomic heterogeneities in single cell level. It is an important step for studying cell sub-populations and lineages based on scRNA-seq data by finding an effective low-dimensional representation and visualization of the original data. The scRNA-seq data are much noiser than traditional bulk RNA-Seq: in the single cell level, the transcriptional fluctuations are much larger than the average of a cell population and the low amount of RNA transcripts will increase the rate of technical dropout events. In this study, we proposed VASC (deep Variational Autoencoder for scRNA-seq data), a deep multi-layer generative model, for the unsupervised dimension reduction and visualization of scRNA-seq data. It can explicitly model the dropout events and find the nonlinear hierarchical feature representations of the original data. Tested on twenty datasets, VASC shows superior performances in most cases and broader dataset compatibility compared with four state-of-the-art dimension reduction methods. Then, for a case study of pre-implantation embryos, VASC successfully re-establishes the cell dynamics and identifies several candidate marker genes associated with the early embryo development.

bioinformatics↗