Biology subjects

Cai, B.

Publications and source records attributed to Cai, B..

41 records · Page 3Linked to original sources

bioRxiv2019

Moxifloxacin efficacy against Mycobacterium abscessus in vivo using zebrafish model

Moxifloxacin (MFX) showed good activity in vitro against Mycobacterium abscessus (M. abscessus) and was suggested as one of the antibiotic regimens for adults with M. abscessus disease. However, some other studies showed that MFX showed less or none activity against M. abscessus. In our study we aim to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. MIC of each drugs were determined by broth microdilution method. M. abscessus labeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activity in vitro. But in vivo MFX showed limited restriction to M. abscessus. The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy on Mycobacterium abscessus in vivo using ZF model. MFXs activity in vivo need to be confirmed.

microbiology↗

bioRxiv2019

Systematic Integration of Structural and Functional Data into Multi-Scale Models of Mouse Primary Visual Cortex

AO_SCPLOWBSTRACTC_SCPLOWStructural rules underlying functional properties of cortical circuits are poorly understood. To explore these rules systematically, we integrated information from extensive literature curation and large-scale experimental surveys into a data-driven, biologically realistic model of the mouse primary visual cortex. The model was constructed at two levels of granularity, using either biophysically-detailed or point-neurons, with identical network connectivity. Both variants were compared to each other and to experimental recordings of neural activity during presentation of visual stimuli to awake mice. While constructing and tuning these networks to recapitulate experimental data, we identified a set of rules governing cell-class specific connectivity and synaptic strengths. These structural constraints constitute hypotheses that can be tested experimentally. Despite their distinct single cell abstraction, spatially extended or point-models, both perform similarly at the level of firing rate distributions. All data and models are freely available as a resource for the community.

neuroscience↗

bioRxiv2019

Clinical manifestations and phenotypic analysis of new ANK1 gene mutations in 12 Chinese children with hereditary spherocytosis

ObjectiveTo summarize the clinical features and laboratory examination of ANK1 gene in 12 children with hereditary spherocytosis in China, and to determine the genetic mutations in those children.\n\nMethodsThe clinical data of children and their parents were collected and analyzed. The sequence of related genes was analyzed by second-generation sequencing technology. The suspected pathogenic mutations were detected by Sanger sequencing\n\nResultsNew mutations in the coding region of ANK1 was detected in 12 patients, which caused amino acid changes in the gene encoding, causing structural changes or loss of function.\n\nConclusionANK1 (c.1914_c.1918delTTTG), ANK1 (c.399T>G), ANK1 (c.1564delC), ANK1 (c.4439dupA ), ANK1 (c.4510_4513del), ANK1 (c.2961delC), ANK1 (c.2142dupT), ANK1 (c.2858+1G>C), ANK1 (c.3235delG), ANK1 (c.4739A>G), ANK1 (c.2638-2 A>G), ANK1 (c. 4739A>G) mutations in the coding region of the gene are the cause of suspicious disease in these 12 Chinese children. At the same time, second-generation gene sequencing technology is an effective means of confirming HS. Different types of mutations (P=0.388)and different mutation areas (P=0.660)had no significant effect on the severity of anemia. The 12 gene mutation sites in this study have not been included in the human genome database, dbSNP (v138) and ExAC databases. The new ANK1 gene mutations found in HS children can provide further exploration of the genetic etiology of HS in Chinese population.

genetics↗

bioRxiv2019

Membrane association of VAMP2 SNARE motif in cells and its regulation by different lipid phases of synaptic vesicle membrane

Vesicle associated membrane protein 2 (VAMP2) contains a conserved SNARE motif that forms helix bundles with the homologous motifs of syntaxin-1 and SNAP25 to assemble into a SNARE complex for the exocytosis of synaptic vesicles (SV). Prior to SNARE assembly, the structure of VAMP2 is unclear. Here, using in-cell NMR spectroscopy, we described the dynamic membrane association of VAMP2 SNARE motif in mammalian cells at atomic resolution, and further tracked the intracellular structural changes of VAMP2 upon the lipid environmental changes. The underlying mechanistic basis was then investigated by solution NMR combined with mass-spectrometry-based lipidomic profiling. We analyzed the lipid compositions of lipid-raft and non-raft phases of SV membrane and revealed that VAMP2 configures distinctive conformations in different phases of SV membrane. The phase of cholesterol-rich lipid rafts could largely weaken the association of SNARE motif with SV membrane and thus, facilitate vesicle docking; While in the non-raft phase, the SNARE motif tends to hibernate on SV membrane with minor activity. Our work provides a spatial regulation of different lipid membrane phases to the structure of core SNARE proteins, which deepens our knowledge on the modulation of SNARE machinery.

biophysics↗

bioRxiv2018

Base pair editing of goat embryos: nonsense codon introgression into FGF5 to improve cashmere yield

The ability to alter single bases without DNA double strand breaks provides a potential solution for multiplex editing of livestock genomes for quantitative traits. Here, we report using a single base editing system, Base Editor 3 (BE3), to induce nonsense codons (C-to-T transitions) at four target sites in caprine FGF5. All five progenies produced from microinjected single-cell embryos had alleles with a targeted nonsense mutation and yielded expected phenotypes. The effectiveness of BE3 to make single base changes varied considerably based on sgRNA design. Also, the rate of mosaicism differed between animals, target sites, and tissue type. PCR amplicon and whole genome resequencing analyses for off-target changes caused by BE3 were low at a genome-wide scale. This study provides first evidence of base editing in livestock, thus presenting a potentially better method to introgress complex human disease alleles into large animal models and provide genetic improvement of complex health and production traits in a single generation.

genetics↗