Biology subjects

Su, B.

Publications and source records attributed to Su, B..

5 recordsLinked to original sources

bioRxiv2018

Electrospun Cellulose-Silk Composite Nanofibres Direct Mesenchymal Stem Cell Chondrogenesis in the Absence of Biological Stimulation

Smart biomaterials with an inherent stimulating capacity that elicit specific behaviours in lieu of biological prompts would prove advantageous for regenerative medicine applications. Specific blends of the natural polymers cellulose and silk cast as films can drive the chondrogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) upon in vitro culture. However, the true potential of such biomaterials for cartilage tissue engineering can be realised upon its three-dimensional fabrication. In this work we employ an electrospinning technique to model the in vivo nanofibrous extracellular matrix (ECM). Cellulose and silk polymers at a mass ratio of 75:25 were regenerated using a trifluoroacetic acid and acetic acid cosolvent system. This natural polymer composite was directly electrospun for the first time, into nanofibers without post-spun treatment. The presence and size of fibre beading was influenced by environmental humidity. The regenerated composite retained the key chemical functionalities of its respective components. Biocompatibility of the natural polymer composite with hMSCs was demonstrated and its inherent capacity to direct chondrogenic stem cell differentiation, in the absence of stimulating growth factors, was confirmed. This physical chondrogenic stimulation was countered biochemically using fibroblast growth factor-2 (FGF-2), a growth factor used to enhance the proliferation of hMSCs. The newly fabricated scaffold provides the foundation for designing a robust, self-inductive, and cost-effective biomimetic biomaterial for cartilage tissue engineering.

bioengineering↗

bioRxiv2018

Structural and biochemical characterization on the cognate and heterologous interactions of the MazEF-mt9 TA system

The toxin-antitoxin (TA) modules widely exist in bacteria, and their activities are associated with the persister phenotype of the pathogen Mycobacterium tuberculosis (M. tb). M. tb causes Tuberculosis, a contagious and severe airborne disease. There are ten MazEF TA systems in M. tb, which play important roles in stress adaptation. How the antitoxins antagonize toxins in M. tb or how the ten TA systems crosstalk to each other are of interests, but the detailed molecular mechanisms are largely unclear. MazEF-mt9 is a unique member among the MazEF families due to its tRNase activity, which is usually carried out by the VapC family toxins. Here we present the cocrystal structure of the MazEF-mt9 complex at 2.7 [A]. By characterizing the association mode between the TA pairs through various characterization techniques, we found that MazF-mt9 not only bound its cognate antitoxin, but also the non-cognate antitoxin MazE-mt1, a phenomenon that could be also observed in vivo. Based on our structural and biochemical work, we proposed that the cognate and heterologous interactions among different TA systems work together to relieve MazF-mt9s toxicity to M. tb cells, which may facilitate their adaptation to the stressful conditions encountered during host infection.\n\nIMPORTANCETuberculosis (TB) is one of the most severe contagious diseases. Caused by Mycobacterium tuberculosis (M. tb), it poses a serious threat to human health. Additionally, TB is difficult to cure because of the multipledrug-resistant (MDR) and extensively drug-resistant (XDR) M. tb strains. Toxin-antitoxin (TA) systems have been discovered to widely exist in prokaryotic organisms with diverse roles, normally composed of a pair of molecules that antagonize each other. M. tb has ten MazEF systems, and some of them have been proved to be directly associated with the genesis of persisters and drug-resistance of M. tb. We here report the MazEF-mt9 complex structure, and thoroughly characterized the interactions between MazF-mt9 with MazEs within or outside the MazEF-mt9 family. Our study not only revealed the crosstalks between TA families and its significance to M. tb survival but also offers insights into potential anti-TB drug design.

biochemistry↗

bioRxiv2018

Spatio-temporal variability of soil nutrients and the responses of growth during growth stages of winter wheat in the north of China

Study on soil nutrient variability and its effect on the growth and development of crop under traditional tillage mode is the foundation to comprehensively implement the precision agriculture policy on the field scale and crop excellent management. In this paper, a winter wheat field of 28.5 hm2 under traditional cultivation model in Tianzhuang town of Huantai county was selected as the research area. Sampling by mesh point method (60x60m), the variation characteristics of soil available nitrogen (AN), available phosphorus (AP) and available potassium (AK) in the before sowing, reviving stage, jointing stage, filling stage of winter wheat were analyzed by the method of geostatistics and GIS. At the same time, Pearson correlation analysis was used to study the response of wheat growth and development to soil nutrient variation. As the growth period goes by, 1) each nutrient showed low-high-low and moderate variability. AN and AK had the highest content at reviving stage, while AP at jointing stage, as turning point. The order of variability of each nutrient was AN>AP>AK. 2) The difference of nutrient variation first increased and then decreased, and showed medium to strong spatial correlation.\n\nThree nutrients in the before sowing stage were strong spatial correlation, and the reviving stage was medium spatial correlation, to the jointing and filling stages, AN was medium spatial correlation, AP and AK were strong spatial correlation. The spatial correlation of each nutrients was the weakest in the reviving stage, and AN was the strongest in the before sowing stage, while AP and AK were strongest in the jointing stage. The spatial correlation of each soil nutrients decreased from before sowing to reviving stage, jointing stage to filling stage, and the spatial correlation increased from reviving stage to jointing stage. 3) Soil nutrient content first increased and then decreased, and the grade of nutrient gradually decreased. 4) The correlation between soil nutrients and wheat growth was gradually increasing. AN had the highest correlation with wheat growth, followed by AK and AP lowest. The effect of soil nutrients on the growth of wheat at the reviving stage was higher than that of the current nutrient, and the growth of wheat at jointing stage was mainly influenced by the current nutrient, while the growth of wheat at the filling period was both influenced by the nutrient content of the last and the current period; the date to supplement fertilizer should be postponed properly. In this study, the soil nutrient dynamics and its influence on the growth of wheat during the winter wheat growth period under the traditional field model were well understood, which could provide a theoretical basis for the precision management of soil nutrients in the northern winter wheat area with relatively uniform planting environment and cultivation management.

scientific communication and education↗

bioRxiv2018

Identifying Lineage-specific Targets of Darwinian Selection by a Bayesian Analysis of Genomic Polymorphisms and Divergence from Multiple Species

We present a method that jointly analyzes the polymorphism and divergence sites in genomic sequences of multiple species to identify the genes under positive or negative selection and pinpoints the occurrence time of selection to a specific lineage of the species phylogeny. This method integrates population genetics models using the Bayesian Poisson random field framework and combines information over all gene loci to boost the power to detect selection. The method provides posterior distributions of the fitness effects of each gene along with parameters associated with the evolutionary history, including the species divergence times and effective population sizes of external species. A simulation is performed, and the results demonstrate that our method provides accurate estimates of these population genetic parameters.\n\nThe proposed method is applied to genomic sequences of humans, chimpanzees, gorillas and orangutans, and a spatial and temporal map is constructed of the natural selection that occurred during the evolutionary history of the four Hominidae species. In addition to FOXP2 and other known genes, we identify a new list of lineage-specific targets of Darwinian selection. The positively selected genes in the human lineage are enriched in pathways of gene expression regulation, immune system, metabolism etc. Interestingly, some pathways, such as gene expression, are significantly enriched with positively selected genes, whereas other pathways, such as metabolism, are enriched with both positively and negatively selected genes. Our analysis provides insights into Darwinian evolution in the coding regions of humans and great apes and thus serves as a basis for further molecular and functional studies.

genomics↗

bioRxiv2018

Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect remains a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, no comprehensive in vivo off-target assessment has been conducted in NHPs. Here we performed whole genome trio sequencing of Cas9-treated monkeys. We found they only carried a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected mutations were detected.

bioengineering↗