Biology subjects

Jiang, N.

Publications and source records attributed to Jiang, N..

7 recordsLinked to original sources

bioRxiv2018

A conserved morphogenetic mechanism for epidermal ensheathment of nociceptive sensory neurites

Interactions between epithelial cells and neurons influence a range of sensory modalities including taste, touch, and smell. Vertebrate and invertebrate keratinocytes/keratinocyte-like epidermal cells ensheath peripheral arbors of somatosensory neurons, including nociceptors, yet the developmental origins and functional roles of this ensheathment are largely unknown. Here, we describe an evolutionarily conserved morphogenetic mechanism for epidermal ensheathment of somatosensory neurites. We found that somatosensory neurons in Drosophila and zebrafish induce formation of epidermal sheaths, which wrap neurites of different types of neurons to different extents. Neurites induce formation of plasma membrane phosphatidylinositol 4,5-bisphosphate microdomains at nascent sheaths, followed by a filamentous actin network, and recruitment of junctional proteins that likely form autotypic junctions to seal sheaths. Finally, blocking epidermal sheath formation destabilized dendrite branches and reduced nociceptive sensitivity in Drosophila. Epidermal somatosensory neurite ensheathment is thus a deeply conserved cellular process that contributes to the morphogenesis and function of nociceptive sensory neurons.

neuroscience↗

bioRxiv2018

High-resolution 4D spatiotemporal analysis reveals the contributions of local growth dynamics to contrasting maize root system architectures

Root systems are branched networks that develop from simple growth properties of their individual roots. Yet a mature maize root system has many thousands of roots that each interact with soil structures, water and nutrient patches, and microbial ecologies in the micro-environments surrounding each root tip. Although the plasticity of root growth to these and other environmental factors is well known, how the many local processes contribute over time to global features of root system architecture is hardly understood. We employ an automated 3D root imaging pipeline to capture the growth of maize roots every four hours throughout seven days of seedling development. We model the contrasting architectures of two maize inbred genotypes and their hybrid to derive key parameters that distinguish complex growth patterns as a function of time. The statistical characteristics of local root growth defined the global system properties despite a large range of trait values. \"Computational dissection\" of a single root from each root system identified differences in the size of the root branching zone and lateral branching densities, but not radial patterns, that drove the contrasting root architectures from seedling to maturity. X-ray imaging of mature field-grown root crowns showed that seedling growth trajectories persisted throughout development and could predict eventual architectures, suggesting a strong genetic basis. The work connects individual and systemwide scales of root growth dynamics, providing the means for a function-valued approach to understanding the genetic and genetic x environment conditioning of root growth that will enable breeding for enhanced root traits.\n\nSIGNIFICANCE STATEMENTWhen and where roots grow determines their ability to capture short-lived and patchy water and nutrient resources to support the aboveground organs of the plant. Roots have no known long-distance external sensing mechanisms, but form branched networks that blindly explore the soil and respond to encountered local stimuli. How global architectures form from the many thousands of these local responses, and how they are controlled genetically are major open questions. Here we quantify differences in local root growth patterns of two inbred genotypes of maize that control contrasting systemwide properties. Measurements at the seedling stage were highly correlated with the complex architectures of mature root systems, paving the way for the development of crops with greater resource uptake capacity.

plant biology↗

bioRxiv2018

Meta-microRNAs as potential noninvasive markers for early diagnosis of Alzheimer’s disease

IntroductionThe aim of this study was to investigate the potential role of a microRNA panel as early diagnostic markers for Alzheimers disease (AD).\n\nMethodsThe differentially expressed serum microRNAs were screened with microarray among cognitively normal controls (CNC), mild cognitive impairment (MCI), and AD. QRT-PCR assay was applied to evaluate differentially expressed microRNAs with two independent cohorts including 202 participants. Logistic regression model based on microRNA panel was constructed using a training cohort and then validated using an independent cohort.\n\nResultsFirst, four differentially expressed serum microRNAs (let-7g, miR-197, miR-126 and miR-29a) were found, which expressions were positively correlated with mini mental state examination (MMSE) score. Second, a microRNA panel with the four microRNAs demonstrated good diagnostic performance for MCI and AD with 84% and 92% accuracy. Third, when combined with MMSE score, the diagnostic performance of the microRNA panel was further improved.\n\nDiscussionBlood microRNAs are potential AD biomarkers that may lead to new diagnostic strategies.

neuroscience↗

bioRxiv2017

Decoupling cellular response to topography and stiffness in three dimensions

Biophysical aspects of in vivo tissue microenvironments include microscale mechanical properties, fibrillar alignment, and architecture or topography of the extracellular matrix (ECM). These aspects act in concert with chemical signals from a myriad of diverse ECM proteins to provide cues that drive cellular responses. Here, we used a bottom-up approach to build fibrillar architecture into 3D amorphous hydrogels using magnetic-field driven assembly of paramagnetic colloidal particles functionalized with three types of human ECM proteins found in vivo. We investigated if cells cultured in matrices comprised of fibrils of the same size and arranged in similar geometries will show similar behavior for each of the ECM proteins tested. We were able to resolve spatial heterogeneities in microscale mechanical properties near aligned fibers that were not observed in bulk tissue mechanics. We then used this platform to examine factors contributing to cell alignment in response to topographical cues in 3D laminin-rich matrices. Multiple human cell lines extended protrusions preferentially in directions parallel or perpendicular to aligned fibers independently of the ECM coating. Focal adhesion proteins, as measured by paxillin localization, were mainly diffuse in the cytoplasm, with few puncta localized at the protrusions. Integrin {beta}1 and fascin regulated protrusion extension but not protrusion alignment. Myosin II inhibition did not reduce observed protrusion length. Instead, cells with reduced myosin II activity generated protrusions in random orientations when cultured in hydrogels with aligned fibers. Similarly, myosin II dependence was observed in vivo, where cells no longer aligned along the abluminal surfaces of blood vessels upon treatment with blebbistatin. These data suggest that myosin II can regulate sensing of topography in 3D engineered matrices for both normal and transformed cells.

bioengineering↗

bioRxiv2017

COLT-Viz: Interactive Visualization of Antibody Lineage Trees

Many tools have been developed to visualize phylogenetic trees, which is a traditional technique for evolutionary tree analysis. However, due to the unique characteristics of antibody lineage trees, the phylogenetic method cannot adequately construct proper tree structures for antibody lineages, and many other tools have been developed to address this problem. However, there still lacks of an adequate tool to visualize the resulted antibody lineage structures that are more complicated than phylogenetic trees. In addition, high-throughput sequencing-based antibody repertoire profiling enables the counting of the number of transcripts associated with individual antibody sequences, thus more dimensions need to be encoded in the tree structure visualization. Further, users may wish to manually adjust the tree structure for a special context. When doing so, they may wish to maintain some biological constraints that are applicable in antibody lineage tree structure, such as isotype switching constraints or different sampling constraints. Here, we report an interactive visualization tool (COLT-Viz) designed to display the number of RNA copies, number of somatic hypermutations, and sample collection time associated with each antibody sequence as well as the distance to neighboring sequences for each antibody sequence in the lineage. COLT-Viz also allows users to interactively visualize and edit antibody lineage structures while giving users the option to automatically check biological constraints on the edited structures to ensure accuracy. COLT-Viz takes JSON text format as input files and can easily be used to visualize networks with or without the biological constraints. We believe the amount of information that can be displayed for complex antibody lineages, the interactive interface, and the option of checking for biological constraints make COLT-Viz a versatile tool for antibody lineage tree visualization that will guide further biological discoveries.

bioinformatics↗

bioRxiv2017

Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

Accurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important to the understanding of the repertoire response to infections and vaccinations. Here, we describe an accurate and high-coverage repertoire sequencing method, MIDCIRS, which uses as few as 1,000 naive B cells. Using it, we studied age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12 - 47 months old) with 4-8 ml of blood draws. Unexpectedly, we discovered high levels of somatic hypermutation (SHM) in infants as young as three months old. Antibody clonal lineage analysis revealed that both infants and toddlers increase SHM levels upon infection and memory B cells isolated from pre-malaria samples in malaria-experienced individuals continue to induce SHMs upon malaria rechallenge. These results highlight the vast potential of antibody repertoire diversification in infants and toddlers that has not been realized previously.

immunology↗

bioRxiv2017

LTR_retriever: A Highly Accurate And Sensitive Program For Identification Of LTR Retrotransposons

Long terminal-repeat retrotransposons (LTR-RTs) are prevalent in plant genomes. Identification of LTR-RTs is critical for achieving high-quality gene annotation. Based on the well-conserved structure, multiple programs were developed for de novo identification of LTR-RTs; however, these programs are associated with low specificity and high false discovery rate (FDR). Here we report LTR_retriever, a multithreading empowered Perl program that identifies LTR-RTs and generates high-quality LTR libraries from genomic sequences. LTR_retriever demonstrated significant improvements by achieving high levels of sensitivity (91.8%), specificity (94.7%), accuracy (94.3%), and precision (90.6%) in model plants. LTR_retriever is also compatible with long sequencing reads. With 40k self-corrected PacBio reads equivalent to 4.5X genome coverage in Arabidopsis, the constructed LTR library showed excellent sensitivity and specificity. In addition to canonical LTR-RTs with 5'-TG..CA-3' termini, LTR_retriever also identifies non-canonical LTR-RTs (non-TGCA), which have been largely ignored in genome-wide studies. We identified seven types of non-canonical LTRs from 42 out of 50 plant genomes. The majority of non-canonical LTRs are Copia elements, with which the LTR is four times shorter than that of other Copia elements, which may be a result of their target specificity. Strikingly, non-TGCA Copia elements are often located in genic regions and preferentially insert nearby or within genes, indicating their impact on the evolution of genes and potential as mutagenesis tools.

genomics↗