The functional evolution of photolyase related to DNA repair and circadian clock in vertebrates

The cryptochrome/photolyase family (CPF) is a group of highly conserved flavoproteins that harness sunlight to enable various biological processes including hotoreception, DNA damage repair and circadian clock entrainment. Photoreactivation, one of the principal DNA repair systems is catalysed by the flavoprotein enzymes called photolyases. These use light as a driving force to repair UV-induced DNA damage and are encountered in almost all prokaryotes and eukaryotes with the notable, strange exception of placental mammals. The Foulkes lab’s previous work has demonstrated that the Somalian cavefish, Phreatichthys andruzzii, which has evolved in a perpetually dark subterranean environment for millions of years, has greatly attenuated photoreactivation as the result of accumulating truncation mutations in the 6-4 and DASH photolyase genes. However, the CPD photolyase gene remains intact and encodes a protein that can still catalyze DNA repair. Is there selective pressure acting to maintain CPD photolyase function despite the complete absence of sunlight? Here I have used a comparative approach involving photolyase mutant lines generated in medaka as well as zebrafish and cavefish, to reveal that CPD photolyase confers increased cell survival and enhanced DNA repair capacity upon exposure of cells to oxidative stress. Furthermore, I demonstrate that light does not influence CPD photolyase-induced protection against ROS-induced mortality. Interestingly, in the absence of light, ROS can induce limited CPD production however, it remains unclear whether CPD photolyase may be able to catalyze the repair of this DNA damage under constant darkness. My results may account for why the CPD photolyase gene is conserved in the Somalian cavefish. Furthermore, this may provide clues as to how and why photolyase genes have been lost during placental mammal evolution. It has been documented that in various organisms, many CPF flavoproteins possess a bifunctional property, specifically being not only implicated in DNA repair but also serving as circadian clock components. In this study, I have shown that the loss of 6-4 photolyase function disrupts rhythmic expression of certain clock genes in a gene- and tissue-specific manner. Furthermore, I have shown that 6-4 photolyase participates in the transcription control of circadian clock genes via repression of transactivation of the CLOCK-BMAL complex occurring at E-box enhancer elements and via enhancing TEF transactivation at light-responsive D-box enhancer elements. However, the precise nature of the physical interaction between 6-4 photolyase and the CLOCK-BMAL heterodimer and the TEF protein remains unclear. My discovery provides new insight into the basis of the divergent function of CPF members in vertebrates. Furthermore, more generally the results obtained in this project reveal how the evolution of the CPF family of flavoproteins may have been shaped by adaptation to extreme environmental conditions

Optimization on emergency materials dispatching considering the characteristics of integrated emergency response for large-scale marine oil spills

Many governments have been strengthening the construction of hardware facilities and equipment to prevent and control marine oil spills. However, in order to deal with large-scale marine oil spills more efficiently, emergency materials dispatching algorithm still needs further optimization. The present study presents a methodology for emergency materials dispatching optimization based on four steps, combined with the construction of Chinese oil spill response capacity. First, the present emergency response procedure for large-scale marine oil spills should be analyzed. Second, in accordance with different grade accidents, the demands of all kinds of emergency materials are replaced by an equivalent volume that can unify the units. Third, constraint conditions of the emergency materials dispatching optimization model should be presented, and the objective function of the model should be postulated with the purpose of minimizing the largest sailing time of all oil spill emergency disposal vessels, and the difference in sailing time among vessels that belong to the same emergency materials collection and distribution point. Finally, the present study applies a toolbox and optimization solver to optimize the emergency materials dispatching problem. A calculation example is presented, highlighting the sensibility of the results at different grades of oil spills. The present research would be helpful for emergency managers in tackling an efficient materials dispatching scheme, while considering the integrated emergency response procedure.Peer ReviewedPostprint (published version

Nonlinear macromodel based on Krylov subspace for micromixer of the microfluidic chip

The simulation of MEMS (Micro-Electro-Mechanical-System) containing fluid field could not be well performed by conventional numerical analysis methods. The micro flow field characteristics can be simulated by using macromodel including a nonlinear analysis. This paper set up the macromodel of the micromixer of the microfluidic chip using Krylov subspace projection method. The system functions were assembled through finite element analysis using COMSOL. We took the flow field-concentration field analysis for micromixer finite element model. The finite element functions order is reduced by second-order Krylov subspace projection method based on Lanczos algorithm. It can be shown that the simulation results obtained by using the macromodel are highly consistent with the results of finite element analysis. The calculation using the macromodel is two orders of magnitude faster than the calculation performed by the finite element analysis method. This macromodel should facilitate the design of microfluidic devices with sophisticated channel networks

A note on the total chromatic number of Halin graphs with maximum degree 4

AbstractIn this paper, we prove that χT(G) = 5 for any Halin graph G with Δ(G) = 4, where Δ(G) and χT(G) denote the maximal degree and the total chromatic number of G, respectively

A Causal Intervention Scheme for Semantic Segmentation of Quasi-periodic Cardiovascular Signals

Precise segmentation is a vital first step to analyze semantic information of cardiac cycle and capture anomaly with cardiovascular signals. However, in the field of deep semantic segmentation, inference is often unilaterally confounded by the individual attribute of data. Towards cardiovascular signals, quasi-periodicity is the essential characteristic to be learned, regarded as the synthesize of the attributes of morphology (Am) and rhythm (Ar). Our key insight is to suppress the over-dependence on Am or Ar while the generation process of deep representations. To address this issue, we establish a structural causal model as the foundation to customize the intervention approaches on Am and Ar, respectively. In this paper, we propose contrastive causal intervention (CCI) to form a novel training paradigm under a frame-level contrastive framework. The intervention can eliminate the implicit statistical bias brought by the single attribute and lead to more objective representations. We conduct comprehensive experiments with the controlled condition for QRS location and heart sound segmentation. The final results indicate that our approach can evidently improve the performance by up to 0.41% for QRS location and 2.73% for heart sound segmentation. The efficiency of the proposed method is generalized to multiple databases and noisy signals.Comment: submitted to IEEE Journal of Biomedical and Health Informatics (J-BHI