Biology subjects

Bai, L.

Publications and source records attributed to Bai, L..

7 recordsLinked to original sources

bioRxiv2018

Complement 3 signaling is necessary for the developmental refinement of olfactory bulb circuitry

The olfactory system depends upon organizational maps that are developmentally refined and maintained, however the cellular and molecular mechanisms that underlie these processes are unknown. Studies have shown that microglia and complement molecules are important for the developmental refinement of circuitry within the visual system, thus we asked whether they played a similar role in the olfactory system through the formation of the olfactory bulb (OB) maps, the glomerular and intrabulbar maps. Our findings revealed that microglia in mature animals engulf olfactory sensory neuron (OSN) axons and the synaptic terminals of tufted cells in the glomerular and intrabulbar maps respectively, suggesting microglia could anatomically shape the mature OB circuitry. To determine the mechanisms underlying this axonal pruning activity we used complement 3 (C3) and complement receptor 3 (CR3) knockout mice to investigate if C3 signaling was necessary for precise OB map development. Our results demonstrate that glomerular and intrabulbar map disorganization as typically present in early postnatal mice persists into adulthood when C3 signaling is disrupted. These data clearly establish the C3/CR3 pathway as necessary for the proper developmental refinement of both olfactory maps. We further present the olfactory system as a unique platform to study the role of glia in the development and adult refinement of regenerating circuits.

neuroscience↗

bioRxiv2018

Electron Microscopy Analysis of hAPP-Induced Neurodegeneration in the Glomerular Network

Loss of smell is an early indicator of Alzheimers disease (AD), making the olfactory system an accessible model to study the effect of AD related proteins such as Amyloid Precursor Protein (APP). The regenerative capacity of the system further enables studies of circuit recovery after APP-induced degeneration. While the cellular effects of APP are well documented, little is known about its effects on brain circuits at the ultrastructural level. To study circuitry changes, we overexpressed humanized APP with familial AD mutations (hAPP) in olfactory sensory neurons and performed serial electron microscopy on olfactory bulb glomeruli from both control and hAPP expressing mice. We found that hAPP-expressing mice showed a striking decrease in glomerular connectivity along with widespread changes of subcellular structures. By then turning off hAPP expression for 6 weeks we tested the capacity of glomerular circuits to recover and found clear restoration of both connectivity and subcellular features, including an increase in post-synaptic density to above the control level. These data provide an important ultrastructural view of olfactory regions associated with AD and suggest that circuit recovery is possible in brain tissue that has experienced APP-induced neurodegeneration.

neuroscience↗

bioRxiv2018

Dissociation rate compensation mechanism for budding yeast pioneer transcription factors

Nucleosomes restrict the occupancy of most transcription factors (TF) by reducing binding and accelerating dissociation, while a small group of TFs have high affinities to nucleosome-embedded sites and facilitate nucleosome displacement. To mechanistically understand this process, we investigated two S. cerevisiae TFs, Reb1 and Cbf1. We show these factors bind their sites within nucleosomes with similar affinities to naked DNA, trapping a partially unwrapped nucleosome without histone eviction. Both the binding and dissociation rates of Reb1 and Cbf1 are significantly slower at the nucleosomal sites relative to DNA, demonstrating that the high affinities are achieved by increasing the dwell time on nucleosomes to compensate for reduced binding. Reb1 also shows slow migration rate in the yeast nuclei. These properties are similar to human pioneer factors (PFs), suggesting the mechanism of nucleosome targeting is conserved from yeast to human.

molecular biology↗

bioRxiv2018

An improved high-quality genome assembly and annotation of Qingke, Tibetan hulless barley

BackgroundThe Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called \"Qingke\" in Chinese and \"Ne\" in Tibetan, is the staple food for Tibetans and an important livestock feed in the Tibetan Plateau. The Tibetan hulless barley in China has about 3500 years of cultivation history, mainly produced in Tibet, Qinghai, Sichuan, Yunnan and other areas. In addition, Tibetan hulless barley has rich nutritional value and outstanding health effects, including the beta glucan, dietary fiber, amylopectin, the contents of trace elements, which are higher than any other cereal crops.\n\nFindingsHere, we reported an improved high-quality assembly of Tibetan hulless barley genome with 4.0 Gb in size. We employed the falcon assembly package, scaffolding and error correction tools to finish improvement using PacBio long reads sequencing technology, with contig and scaffold N50 lengths of 1.563Mb and 4.006Mb, respectively, representing more continuous than the original Tibetan hulless barley genome nearly two orders of magnitude. We also re-annotated the new assembly, and reported 61,303 stringent confident putative protein-coding genes, of which 40,457 is HC genes. We have developed a new Tibetan hulless barley genome database (THBGD) to download and use friendly, as well as to better manage the information of the Tibetan hulless barley genetic resources.\n\nConclusionsThe availability of new Tibetan hulless barley genome and annotations will take the genetics of Tibetan hulless barley to a new level and will greatly simplify the breeders effort. It will also enrich the granary of the Tibetan people.

genomics↗

bioRxiv2018

Fine Tuning of Histone Demethylase KDM6A/B Improves the Development of Nuclear Transfer Embryo

Despite the success of the production of animals by somatic cell nuclear transfer (SCNT) in many species, the method is limited by a low efficiency. After zygotic genome activation (ZGA), a large number of endogenous retroviruses (ERVs) are expressed, including the murine endogenous retrovirus-L (MuERVL/MERVL). In this study, we generated a series of MERVL-reporter mouse strains to detect the ZGA event in embryos. We found that the majority of SCNT embryos exhibited ZGA failure, and histone H3 lysine 27 trimethylation (H3K27me3) prevented SCNT reprogramming. Overexpression of the H3K27me3-specific demethylase KDM6A, but not KDM6B, improved the efficiency of SCNT. Conversely, knockdown KDM6B not only facilitate ZGA, but also impede ectopic Xist expression in SCNT reprogramming. Furthermore, the knockdown of KDM6B increased the rate of SCNT-derived Duchenne muscular dystrophy embryonic stem cell establishment, indicate that these results not only provide insight into the mechanisms underlying failures of SCNT, but also may extend the applications of SCNT.

cell biology↗

bioRxiv2018

Extracellular HBV RNAs are heterogeneous in length and circulate as virions and capsid-antibody-complexes in chronic hepatitis B patients

Extracellular HBV RNA has been detected in both HBV-replicating cell culture media and sera from chronic hepatitis B (CHB) patients, but its exact origin and composition remain controversial. Here, we demonstrated that extracellular HBV RNA species were of heterogeneous lengths, ranging from the length of pregenomic RNA to a few hundred nucleotides. In cell models, these RNAs were predominantly associated with naked capsids although virions also harbored a minority of them. Moreover, HBV RNAs in hepatitis B patients blood circulation were localized in unenveloped capsids in the form of capsid-antibody-complexes (CACs) and in virions. Furthermore, we showed that extracellular HBV RNAs could serve as template for viral DNA synthesis. In conclusion, extracellular HBV RNAs mainly consist of pgRNA or the pgRNA species degraded by the RNase H domain of the polymerase in the process of viral DNA synthesis and circulate as CACs and virions. Their presence in the blood circulation of CHB patients may be exploited to develop novel biomarkers for HBV persistence.

microbiology↗

bioRxiv2017

Rapid Whole Brain Imaging Of Neural Activities In Freely Behaving Larval Zebrafish

The internal brain dynamics that link sensation and action are arguably better studied during natural animal behaviors. Here we report on a novel volume imaging and 3D tracking technique that monitors whole brain neural activity in freely swimming larval zebrafish (Danio rerio). We demonstrated the capability of our system through functional imaging of neural activity during visually evoked and prey capture behaviors in larval zebrafish.

neuroscience↗