Biology subjects

Shi, L.

Publications and source records attributed to Shi, L..

259 records · Page 15Linked to original sources

bioRxiv2018

Local Delivery of Stromal Cell-Derived Factor-1α Improves the Pregnancy Rate of Injured Uterus through the Promotion of Endometrial and Vascular Regeneration

Severe infection and mechanical injury of the uterus may lead to infertility and miscarriage. Currently, there is a lack of effective treatment modality for functional repair of uterine injury. To address this clinical challenge, this study aimed to develop a chemotactic composite scaffold by incorporating recombinant human stromal cell-derived factor-1 (rhSDF-1) into a silk fibroin-bacterial cellulose (SF-BC) membrane carrier. A rat model of uterine injury was utilized for this study, which was composed of three groups: blank control, implantation with SF-BC only or SF-BC loaded with rhSDF-1. The tissue regeneration efficacy of the three groups were analyzed and compared. The results showed that SF-BC loaded with rhSDF-1 significantly enhanced endometrial regeneration and arteriogenesis of the injured rat uterus, which led to improved pregnancy outcomes, thus indicating much promise for functional uterine repair and regeneration.

bioengineering↗

bioRxiv2018

SpaRC: Scalable Sequence Clustering using Apache Spark

Whole genome shotgun based next generation transcriptomics and metagenomics studies often generate 100 to 1000 gigabytes (GB) sequence data derived from tens of thousands of different genes or microbial species. De novo assembling these data requires an ideal solution that both scales with data size and optimizes for individual gene or genomes. Here we developed a Apache Spark-based scalable sequence clustering application, SparkReadClust (SpaRC), that partitions the reads based on their molecule of origin to enable downstream assembly optimization. SpaRC produces high clustering performance on transcriptomics and metagenomics test datasets from both short read and long read sequencing technologies. It achieved a near linear scalability with respect to input data size and number of compute nodes. SpaRC can run on different cloud computing environments without modifications while delivering similar performance. In summary, our results suggest SpaRC provides a scalable solution for clustering billions of reads from the next-generation sequencing experiments, and Apache Spark represents a cost-effective solution with rapid development/deployment cycles for similar large scale sequence data analysis problems. The software is available under the Apache 2.0 license at https://bitbucket.org/LizhenShi/sparc.

bioinformatics↗

bioRxiv2018

Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages

The development of malaria parasites throughout their various life cycle stages is controlled by coordinated changes in gene expression. We previously showed that the three-dimensional organization of the P. falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyzed genome organization in the P. falciparum and P. vivax transmission stages. Major changes occurred in the localization and interactions of genes involved in pathogenesis and immune evasion, erythrocyte and liver cell invasion, sexual differentiation and master regulation of gene expression. In addition, we observed reorganization of subtelomeric heterochromatin around genes involved in host cell remodeling. Depletion of heterochromatin protein 1 (PfHP1) resulted in loss of interactions between virulence genes, confirming that PfHP1 is essential for maintenance of the repressive center. Overall, our results suggest that the three-dimensional genome structure is strongly connected with transcriptional activity of specific gene families throughout the life cycle of human malaria parasites.

systems biology↗

bioRxiv2017

Boosting ATM Activity Promotes Longevity in Nematodes and Mice

DNA damage accumulates with age1. However, whether and how robust DNA repair machinery promotes longevity is elusive. Here, we demonstrate that activation of ataxia-telangiectasia mutated (ATM) via low dose of chloroquine (CQ) promotes DNA damage clearance, rescues age-related metabolic shift, and extends lifespan in nematodes and mice. Molecularly, ATM phosphorylates SIRT6 deacetylase and thus prevents MDM2-mediated ubiquitination and proteasomal degradation. Extra copies of Sirt6 in Atm-/- mice extend lifespan, accompanied with restored metabolic homeostasis. In a progeria mouse model with low ATM protein level and DNA repair capacity, the treatment with CQ ameliorates premature aging features and extends lifespan. Thus, our data highlights a pro-longevity role of ATM, for the first time establishing direct causal links between robust DNA repair machinery and longevity, and providing therapeutic strategy for progeria and age-related metabolic diseases.

molecular biology↗

bioRxiv2017

NF90/ILF3 is a transcription factor that promotes proliferation over differentiation by hierarchical regulation in K562 erythroleukemia cells

NF90 and splice variant NF110 are DNA- and RNA-binding proteins encoded by the Interleukin enhancer-binding factor 3 (ILF3) gene that regulate RNA splicing, stabilization and export. The role of NF90 in regulating transcription as a DNA-binding protein has not been comprehensively characterized. Here, ENCODE ChIP-seq identified 9,081 genomic sites specifically bound by NF90/110 in K562 cells. One third of binding sites occurred at promoters of annotated genes. NF90/110 binding colocalized with chromatin marks associated with active promoters and strong enhancers. Comparison with 150 ENCODE ChIP-seq experiments revealed that NF90 clustered with transcription factors exhibiting preference for promoters over enhancers (POLR2A, MYC, YY1). Differential gene expression analysis following shRNA knockdown of NF90 in K562 cells revealed that NF90 directly activates transcription factors that drive growth and proliferation (EGR1, MYC), while attenuating differentiation along erythroid lineage (KLF1). NF90/110 binds chromatin to hierarchically regulate transcription factors to promote proliferation and suppress differentiation.

genetics↗

bioRxiv2017

Positive Feedback Between Contractile Ring Myosin and Ring-Directed Cortical Flow Drives Cytokinesis

During cytokinesis, an equatorial actomyosin contractile ring constricts at a relatively constant overall rate despite its progressively decreasing size. Thus, the per-unit-length rate of ring closure increases as ring perimeter decreases. To understand this acceleration, we monitored cortical surface and ring component dynamics during the first division of the C. elegans embryo. We show that the polar cortex expands during ring constriction to provide the cortical surface area required for division. Polar expansion also allows ring myosin to compress cortical surface along the pole-to-pole axis, leading to a continuous flow of cortical surface into the ring. We propose that feedback between ring myosin and compression-driven cortical flow drives an exponential increase in the amount of ring myosin that maintains the high overall closure rate as ring perimeter decreases. We further show that an analytical mathematical formulation of the proposed feedback, called the Compression Feedback model, recapitulates the experimental observations.\n\nIMPACT STATEMENTDuring cytokinesis, positive feedback between myosin motors in the contractile ring and compression-driven cortical flow along the axis perpendicular to the ring drives constriction rate acceleration to ensure timely cell separation.\n\nMAJOR SUBJECT AREASCell biology, Computational and Systems Biology

cell biology↗

bioRxiv2017

Faster carbon accumulation in global forest soils

Comparing soil organic carbon (SOC) stocks across space and time is a fundamental issue in global ecology. However, the conventional approach fails to determine SOC stock in an equivalent volume of mineral-soil, and therefore, SOC stock changes can be under- or overestimates if soils swell or shrink during forest development or degradation. Here, we propose to estimate SOC stock as the product of mineral-soil mass in an equivalent mineral-soil volume and SOC concentration expressed as g C Kg-1 mineral-soil. This method enables researchers to compare SOC stocks across space and time. Our results show an unaccounted SOC accumulation of 2.4 - 10.1 g C m-2 year-1 in the 1m surface mineral-soils in global forests. This unaccounted SOC amounts to an additional C sink of 0.12 - 0.25 Pg C year-1, which equals 30 - 62% of the previously estimated annual SOC accumulation in global forests. This finding suggests that forest soils are stronger C sinks than previously recognized.

ecology↗