Biology subjects

Zhao, B.

Publications and source records attributed to Zhao, B..

211 records · Page 12Linked to original sources

bioRxiv2018

Differential responses of antioxidants and dehydrin expression in two switchgrass (Panicum virgatum) cultivars contrasting in drought tolerance

Drought stress is a major limiting factor for plant growth and development in many regions of the world. This study was designed to investigate antioxidant metabolism and dehydrin expression responses to drought stress in two switchgrass cultivars (drought tolerant Alamo, and drought sensitive Dacotah) contrasting in drought tolerance. The plants were subjected to well-watered [100% evapotranspiration (ET)] or drought stress (30%-50% ET) conditions for up to 24 d in growth chambers. Drought stress decreased leaf relative water content (RWC), increased leaf electrolyte leakage (EL), leaf malondialdehyde (MDA) content in two cultivars, but Alamo exhibited higher leaf RWC level, lower leaf EL and MDA when compared to Dacotah at 24 d of drought treatment. Drought stress also increased superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activities in two cultivars, Alamo had relatively higher SOD, CAT and APX activities and greater abundance of SOD and APX isozymes than Dacotah at 24 d of drought treatment. Alamo had higher abundance of 55 KDa and 18 KDa dehydrin accumulation than Dacotah under drought treatment. Relative genes expression level of PvCAT1, PvAPX2, PvERD and PvPIP1;5 in Alamo were significantly higher than Dacotah at 24 d of drought treatment. These results suggest that increase in antioxidant enzymes and accumulation of dehydrin were highly related with switchgrass drought tolerance. Antioxidant enzyme activity, isozyme expression and dehydrin abundance could provide a useful screening tool to identify relative drought tolerance in switchgrass cultivars.

plant biology↗

bioRxiv2018

Measuring popularity of ecological topics in a temporal dynamical knowledge network

As interdisciplinary branches of ecology are developing rapidly in the 21st century, contents of ecological researches have become more abundant than ever before. Along with the exponential growth of number of published literature, it is more and more difficult for ecologists to get a clear picture of their discipline. Nevertheless, the era of big data has brought us massive information of well documented historical literature and various techniques of data processing, which greatly facilitates the implementation of bibliometric analysis on ecology. Frequency has long been used as the primary metric in keyword analysis to detect ecological hotspots, however, this method could be somewhat biased. In our study, we have suggested a method called PAFit to measure keyword popularity, which considered ecology-related topics in a large temporal dynamical knowledge network, and found out the popularity of ecological topics follows the \"rich get richer\" and \"fit get richer\" mechanism. Feasibility of network analysis and its superiority over simply using frequency had been explored and justified, and PAFit was testified by its outstanding performance of prediction on the growth of frequency and degree. In addition, our research also encourages ecologists to consider their domain knowledge in a large dynamical network, and be ready to participate in interdisciplinary collaborations when necessary.

ecology↗

bioRxiv2018

Is Polygenic Risk Scores Prediction Good?

Polygenic risk score (PRS) is the state-of-art prediction method for complex traits using summary level data from discovery genome-wide association studies (GWAS). The PRS, as its name suggests, is designed for polygenic traits by aggregating small genetic effects from a large number of causal SNPs and thus is viewed as a powerful method for predicting complex polygenic traits by the genetics community. However, one concern is that the prediction accuracy of PRS in practice remains low with little clinical utility, even for highly heritable traits. Another practical concern is whether genome-wide SNPs should be used in constructing PRS or not. To address the two concerns, we investigate PRS both empirically and theoretically. We show how the performance of PRS is influenced by the triplet (n, p, m), where n, p, m are the sample size, the number of SNPs studied, and the number of true causal SNPs, respectively. For a given heritability, we find that i) when PRS is constructed with all p SNPs (referred as GWAS-PRS), its prediction accuracy is controlled by the p/n ratio; while ii) when PRS is built with a set of top-ranked SNPs that pass a pre-specified threshold (referred as threshold-PRS), its accuracy varies depending on how sparse the true genetic signals are. Only when m is magnitude smaller than n, or genetic signals are sparse, can threshold-PRS perform well and outperform GWAS-PRS. Our results demystify the low performance of PRS in predicting highly polygenic traits, which will greatly increase researchers aware-ness of the power and limitations of PRS, and clear up some confusion on the clinical application of PRS.

genetics↗

bioRxiv2018

Radial F-actin Organization During Early Neuronal Development

The centrosome is thought to be the major neuronal microtubule-organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin-organizing center (Farina et al., 2016), raising the possibility that neuronal development may, in addition, require a centrosome-based actin radial organization. Here we report, using super-resolution microscopy and live-cell imaging, F-actin organization around the centrosome with dynamic F-actin aster-like structures with F-actin fibers extending and retracting actively. Photoconversion/photoactivation experiments and molecular manipulations of F-actin stability reveal a robust flux of somatic F-actin towards the cell periphery. Finally, we show that somatic F-actin intermingles with centrosomal PCM-1 satellites. Knockdown of PCM-1 and disruption of centrosomal activity not only affect F-actin dynamics near the centrosome but also in distal growth cones. Collectively the data show a radial F-actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers; hence sustaining initial neuronal development.

neuroscience↗

bioRxiv2018

Sirt7 regulates circadian phase coherence of hepatic circadian clock via a body temperature/Hsp70-Sirt7-Cry1 axis

The biological clock is generated in the hypothalamic suprachiasmatic nucleus (SCN), which synchronizes peripheral oscillators to coordinate physiological and behavioral activities throughout the body. Disturbance of circadian phase coherence between the central and peripheral could disrupt rhythms and thus cause diseases and aging. Here, we identified hepatic Sirt7 as an early element responsive to light, which ensures the phase coherence in mouse liver. Loss of Sirt7 leads to advanced liver circadian phase; restricted feeding in daytime entrains hepatic clock more rapidly in Sirt7-/- mice compared to wild-types. Molecularly, a light-driven body temperature (BT) oscillation induces rhythmic expression of Hsp70, which binds to and promotes the ubiquitination and proteasomal degradation of Sirt7. Sirt7 rhythmically deacetylates Cry1 on K565/579 and promotes Fbxl3-mediated degradation, thus coupling hepatic clock to the central pacemaker. Together, our data identify a novel BT/Hsp70-Sirt7-Cry1 axis, which transmits biological timing cues from the central to the peripheral and ensures circadian phase coherence in livers.

molecular biology↗

bioRxiv2018

Large-scale neuroimaging and genetic study reveals genetic architecture of brain white matter microstructure

Microstructural changes of white matter (WM) tracts are known to be associated with various neuropsychiatric disorders/diseases. Heritability of structural changes of WM tracts has been examined using diffusion tensor imaging (DTI) in family-based studies for different age groups. The availability of genetic and DTI data from recent large population-based studies offers opportunity to further improve our understanding of genetic contributions. Here, we analyzed the genetic architecture of WM tracts using DTI and single-nucleotide polymorphism (SNP) data of unrelated individuals in the UK Biobank (n [~] 8000). The DTI parameters were generated using the ENIGMA-DTI pipeline. We found that DTI parameters are substantially heritable on most WM tracts. We observed a highly polygenic or omnigenic architecture of genetic influence across the genome as well as the enrichment of SNPs in active chromatin regions. Our bivariate analyses showed strong genetic correlations for several pairs of WM tracts as well as pairs of DTI parameters. We performed voxel-based analysis to illustrate the pattern of genetic effects on selected parts of the tract-based spatial statistics skeleton. Comparing the estimates from the UK Biobank to those from small population-based studies, we illustrated that sufficiently large sample size is essential for genetic architecture discovery in imaging genetics. We confirmed this finding with a simulation study.

genetics↗

bioRxiv2018

Verified the effectiveness of AsCpf1 system in a variety of vertebrate species

CRISPR/Cpf1 system is a novel genomic editing tool. Because of its more sophisticated components, and lower off-target rate, it has the potential to become a better gene-editing tool. Previous reports showed that CRISPR/Cpf1 could work effectively in multiple species. But our data show that AsCpf1 activity has a big difference in different vertebrates. Using in vitro experiments, we finally learned that the difference between species is due to temperature.

developmental biology↗

bioRxiv2017

Heritability of regional brain volumes in large-scale neuroimaging and genetic studies

Brain genetics is an active research area. The degree to which genetic variants impact variations in brain structure and function remains largely unknown. We examined the heritability of regional brain volumes (p ~ 100) captured by single-nucleotide polymorphisms (SNPs) in UK Biobank (n ~ 9000). We found that regional brain volumes are highly heritable in this study population. We observed omni-genic impact across the genome as well as enrichment of SNPs in active chromatin regions. Principal components derived from regional volume data are also highly heritable, but the amount of variance in brain volume explained by the component did not seem to be related to its heritability. Heritability estimates vary substantially across large-scale functional networks and brain regions. The variation in heritability across regions was not related to measurement reliability. Heritability estimates exhibit a symmetric pattern across left and right hemispheres and are consistent in females and males. Our main findings in UK Biobank are consistent with those in Alzheimers Disease Neuroimaging Initiative (n ~ 1100), Philadelphia Neurodevelopmental Cohort (n ~ 600), and Pediatric Imaging, Neurocognition, and Genetics (n ~ 500) datasets, with more stable estimates in UK Biobank.

genetics↗

bioRxiv2017

Deep-learning based hologram classification for molecular diagnostics

Lens-free digital in-line holography (LDIH) is a promising microscopic tool that overcomes several drawbacks (e.g., limited field of view) of traditional lens-based microcopy. However, extensive computation is required to reconstruct object images from the complex diffraction patterns produced by LDIH, which limits LDIH utility for point-of-care applications, particularly in resource limited settings. Here, we describe a deep transfer learning (DTL) based approach to process LDIH images in the context of cellular analyses. Specifically, we captured holograms of cells labeled with molecular-specific microbeads and trained neural networks to classify these holograms without reconstruction. Using raw holograms as input, the trained networks were able to classify individual cells according to the number of cell-bound microbeads. The DTL-based approach including a VGG19 pretrained network showed robust performance even with noisy experimental data. Combined with the developed DTL approach, LDIH could be realized as a low-cost, portable tool for point-of-care diagnostics.

bioengineering↗

bioRxiv2017

A high-throughput analysis method of microdroplet PCR coupled with fluorescence spectrophotometry

Here we report a novel microdroplet PCR method combined with fluorescence spectrophotometry (MPFS), which allows for qualitative, quantitative and high -throughput detection of multiple DNA targets. In this study, each pair of primers was labeled with a specific fluorophore. Through microdroplet PCR, a target DNA was amplified and labeled with the same fluorophore. After products purification, the DNA products tagged with different fluorophores could be analyzed qualitatively by the fluorescent intensity determination. The relative fluorensence unit was also measured to construct the standard curve and to achieve quantitative analysis. In a reaction, the co -amplified products with different fluorophores could be simultaneously analyzed to achieve high -throughput detection. We used four kinds of GM maize as a model to confirm this theory. The qualitative results revealed high specificity and sensitivity of 0.5% (w / w). The quantitative results revealed that the limit of detection was 103copies and with good repeatability. Moreover, reproducibility assay were further performed using four foodborne pathogenic bacteria. Consequently, the same qualitative, quantitative and high-throughput results were confirmed as the four GM maize.

biochemistry↗

bioRxiv2017

Prodomain-Growth Factor Swapping in the Structure of pro-TGF-β1

Transforming growth factor (TGF)-{beta} is synthesized as a proprotein that dimerizes in the endoplasmic reticulum. After processing in the Golgi to cleave the N-terminal prodomain from the C-terminal growth factor (GF) domain in each monomer, pro-TGF-{beta} is secreted and stored in latent complexes. It is unclear which prodomain and GF monomer are linked prior to proprotein convertase (PC) cleavage, and how much conformational change occurs following cleavage. We have determined a structure of pro-TGF-{beta}1 with the PC cleavage site mutated, to mimic the structure of the TGF-{beta}1 proprotein. Our structure demonstrates that the prodomain arm domain in one monomer is linked to the GF that interacts with the arm domain in the other monomer in the dimeric structure, i.e., the prodomain arm domain and GF domain in each monomer are swapped. Swapping has important implications for the mechanism of biosynthesis in the TGF-{beta} family and is relevant to the mechanism for preferential formation of heterodimers over homodimers for some members of the TGF-{beta} family. Our structure also provides comparisons between independent TGF-{beta}1 crystal structures and between human and porcine pro-TGF-{beta}1.

biochemistry↗

bioRxiv2017

Tolloid cleavage activates latent GDF8 by priming the pro-complex for dissociation

Growth differentiation factor 8 (GDF8)/Myostatin is a latent TGF{-}{beta} family member that potently inhibits skeletal muscle growth. Here, we compared the conformation and dynamics of precursor, latent, and Tolloid{-}cleaved GDF8 pro{-}complexes to understand structural mechanisms underlying latency and activation of GDF8. Negative stain electron microscopy (EM) of precursor and latent pro{-}complexes reveals a V{-}shaped conformation that is unaltered by furin cleavage and sharply contrasts with the ring{-}like, cross{-}armed conformation of latent TGF{-}{beta}1. Surprisingly, Tolloid{-}cleaved GDF8 does not immediately dissociate, but in EM exhibits structural heterogeneity consistent with partial dissociation. Hydrogen-deuterium exchange was not affected by furin cleavage. In contrast, Tolloid cleavage, in the absence of prodomain-growth factor dissociation, increased exchange in regions that correspond in pro-TGF-{beta}1 to the 1-helix, latency lasso, and {beta}1 strand in the prodomain and to the {beta}6-7 strands in the growth factor. Thus, these regions are important in maintaining GDF8 latency. Our results show that Tolloid cleavage activates latent GDF8 by destabilizing specific prodomain-growth factor interfaces and primes the growth factor for release from the prodomain.

biochemistry↗

bioRxiv2017

FGF21 regulates melanogenesis in alpaca melanocytes via ERK1/2-Mediated MITF downregulation

Fibroblast growth factor 21 (FGF21) is known as a metabolic regulator to regulate the metabolism of glucose and lipids. However, the underlying mechanism of FGF21 on melanin synthesis remains unknown. Therefore, the current study investigates the effect of FGF21 on melanogenesis in alpaca melanocytes. We transfected the FGF21 into alpaca melanocytes, then detected the melanin contents, protein and mRNA levels of pigmentation-related genes in order to determine the melanogenesis-regulating pathway of FGF21. The results showed that FGF21 overexpression suppressed melanogenesis and decreased the expression of the major target genes termed microphthalmia-associated transcription factor (MITF) and its downstream genes, including tyrosinase (TYR) and tyrosinase-related protein 2 (TRP2). However FGF21 increased the expression of phospho-extracellular signal-regulated kinase (p-Erk1/2). In contrast, FGF21-siRNA, a small interference RNA mediating FGF21 silencing, abolished the inhibition of melanogenesis. Altogether, FGF21 may decrease melanogenesis in alpaca melanocytes via ERK activation and subsequent MITF downregulation, which is then followed by the suppression of melanogenic enzymes and melanin production.

cell biology↗