Biology subjects

Xiao, F.

Publications and source records attributed to Xiao, F..

8 recordsLinked to original sources

bioRxiv2018

Coupled Reaction Networks for Noise Suppression

Noise is intrinsic to many important regulatory processes in living cells, and often forms obstacles to be overcome for reliable biological functions. However, due to stochastic birth and death events of all components in biomolecular systems, suppression of noise of one component by another is fundamentally hard and costly. Quantitatively, a widelycited severe lower bound on noise suppression in biomolecular systems was established by Lestas et. al. in 2010, assuming that the plant and the controller have separate birth and death reactions. This makes the precision observed in several biological phenomena, e.g., cell fate decision making and cell cycle time ordering, seem impossible. We demonstrate that coupling, a mechanism widely observed in biology, could suppress noise lower than the bound of Lestas et. al. with moderate energy cost. Furthermore, we systematically investigate the coupling mechanism in all two-node reaction networks, showing that negative feedback suppresses noise better than incoherent feedforward achitectures, coupled systems have less noise than their decoupled version for a large class of networks, and coupling has its own fundamental limitations in noise suppression. Results in this work have implications for noise suppression in biological control and provide insight for a new efficient mechanism of noise suppression in biology.

systems biology↗

bioRxiv2018

Architectural Principles for Characterizing the Performance of Sequestration Feedback Networks

As we begin to design increasingly complex synthetic biomolecular systems, it is essential to develop rational design methodologies that yield predictable circuit performance. Here we apply theoretical tools from the theory of control and dynamical systems to yield practical insights into the architecture and function of a particular class of biological feedback circuit. Specifically, we show that it is possible to analytically characterize both the operating regime and performance tradeoffs of a sequestration feedback circuit architecture. Further, we demonstrate how these principles can be applied to inform the design process of a particular synthetic feedback circuit.

synthetic biology↗

bioRxiv2018

Stable changing fluid shear stress promotes osteogenesis

ObjectiveBone marrow cells encounter various chemical and mechanical stimuli from the internal environment. In vivo, fluid shear stress (FSS) is one of the primary mechanical stimuli that affect bone marrow-derived mesenchymal stem cells (BMCs) activity. Since various cases of FSS influence BMCs activity differently, the purpose of this study is to determine how BMC activity in osteogenesis and osteoclastgenesis is affected by stable and unstable changing FSS.\n\nMethodBMCs samples from the femur of the mouse, divided in to three groups: stimulate by stable changing FSS, unstable changing FSS, and no FSS. RT-PCR would be applied to detect OPG, RANKL, ALP, OCN, RUNX2, and RANK of all the samples at the 3rd day. Alizarin red staining and TRAP staining would be applied to test all the samples at the 6th day.\n\nResultsThe S group samples showed the lowest level in RANKL mRNA and showed the highest level in OPG mRNA. RANKL/OPG mRNA in the S group was the smallest during three groups. Comparing with the C group samples, RUNX2 mRNA in the S group was increased significantly. RANK mRNA in the C group was three times more than S group. S group had the largest area of mineralized nodules, and largest number of area [≥]100{micro}m, [≥]500{micro}m2 or [≥]1000{micro}m2. The area of positive TRAP stain in S group was the smallest among three groups.\n\nConclusionStable changing FSS significantly increases osteogenesis relating to OPG-RANKL-RANK pathway. Compared with unstable changing FSS, stable changing FSS afford a more appropriate stimulation to osteogenesis.\n\nAbbreviations

cell biology↗

bioRxiv2018

Increased GITRL impairs the function of MDSCs and exacerbates primary Sjögren’s syndrome

It is largely unclear how MDSCs contribute to the development of primary Sjogrens syndrome (pSS). In experimental SS (ESS) mice, MDSCs were significantly increased but exhibited gradually diminished suppressive capacity during the disease progression. The ligand for glucocorticoid-induced TNFR family-related protein (GITRL) was increased with the development of pSS, and the increased GITRL was found to down-regulate the function of MDSCs while blocking GITR signal in MDSCs significantly restored their function and ameliorated ESS progression in mice. In pSS patients, expanded MDSCs expressed lower level of arginase were observed in patients with higher SSDAI. Moreover, the increased GITRL in serum was also found to closely correlate with the aberrant function of MDSCs. Together, our studies have demonstrated a critical role of GITRL in modulating the suppressive capacity of MDSCs in pSS, which may facilitate the validation of GITRL as a therapeutic target for the treatment of pSS.

immunology↗

bioRxiv2018

Robust Perfect Adaptation in Biomolecular Reaction Networks

For control in biomolecular systems, the most basic objective of maintaining a small error in a target variable, say the expression level of some protein, is often difficult due to the presence of both large uncertainty of every type and intrinsic limitations on the controllers implementation. This paper explores the limits of biochemically plausible controller design for the problem of robust perfect adaptation (RPA), biologists term for robust steady state tracking. It is well-known that for a large class of nonlinear systems, a system has RPA iff it has integral feedback control (IFC), which has been used extensively in real control systems to achieve RPA. However, we show that due to intrinsic physical limitations on the dynamics of chemical reaction networks (CRNs), cells cannot implement IFC directly in the concentration of a chemical species. This contrasts with electronic implementations, particularly digital, where it is trivial to implement IFC directly in a single state. Therefore, biomolecular systems have to achieve RPA by encoding the integral control variable into the network architecture of a CRN. We describe a general framework to implement RPA in CRNs and show that well-known network motifs that achieve RPA, such as (negative) integral feedback (IFB) and incoherent feedforward (IFF), are examples of such implementations. We also develop methods to solve the problem of designing integral feedback variables for unknown plants. This standard control notion is surprisingly nontrivial and relatively unstudied in biomolecular control. The methods developed here connect different existing fields and approaches on the problem of biomolecular control, and hold promise for systematic chemical reaction controller synthesis as well as analysis.

synthetic biology↗

bioRxiv2018

Assessment of an organ-specific de novo transcriptome of the nematode trap-crop, Solanum sisymbriifolium

Solanum sisymbriifolium, also known as \"Litchi Tomato\" or \"Sticky Nightshade,\" is an undomesticated and poorly researched plant related to potato and tomato. Unlike the latter species, S. sisymbriifolium induces eggs of the cyst nematode, Globodera pallida, to hatch and migrate into its roots, but then arrests further nematode maturation. In order to provide researchers with a partial blueprint of its genetic make-up so that the mechanism of this response might be identified, we used single molecule real time (SMRT) sequencing to compile a high quality de novo transcriptome of 41,189 unigenes drawn from individually sequenced bud, root, stem, and leaf RNA populations. Functional annotation and BUSCO analysis showed that this transcriptome was surprisingly complete, even though it represented genes expressed at a single time point. By sequencing the 4 organ libraries separately, we found we could get a reliable snapshot of transcript distributions in each organ. A divergent site analysis of the merged transcriptome indicated that this species might have undergone a recent genome duplication and re-diploidization. Further analysis indicated that the plant then retained a disproportionate number of genes associated with photosynthesis and amino acid metabolism in comparison to genes with characteristics of R-proteins or involved in secondary metabolism. The former processes may have given S. sisymbriifolium a bigger competitive advantage than the latter did.

bioinformatics↗

bioRxiv2017

Hard Limits And Performance Tradeoffs In A Class Of Sequestration Feedback Systems

Feedback regulation is pervasive in biology at both the organismal and cellular level. In this article, we explore the properties of a particular biomolecular feedback mechanism implemented using the sequestration binding of two molecules. Our work develops an analytic framework for understanding the hard limits, performance tradeoffs, and architectural properties of this simple model of biological feedback control. Using tools from control theory, we show that there are simple parametric relationships that determine both the stability and the performance of these systems in terms of speed, robustness, steady-state error, and leakiness. These findings yield a holistic understanding of the behavior of sequestration feedback and contribute to a more general theory of biological control systems.

systems biology↗

bioRxiv2017

Accurate typing of class I human leukocyte antigen by Oxford nanopore sequencing

Oxford Nanopore Technologies MinION has expanded the current DNA sequencing toolkit by delivering long read lengths and extreme portability. The MinION has the potential to enable expedited point-of-care human leukocyte antigen (HLA) typing, an assay routinely used to assess the immunological compatibility between organ donors and recipients, but the platforms high error rate makes it challenging to type alleles with clinical-grade accuracy. Here, we developed and validated Athlon, an algorithm that iteratively scores nanopore reads mapped to a hierarchical database of HLA alleles to arrive at a consensus diploid genotype; Athlon achieved a 100% accuracy in class I HLA typing at high resolution.

bioinformatics↗