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Remaking a connection:molecular players involved in post-injury synapse formation

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Neural Regeneration Research 2025年第6期20卷 1719-1720页

作者： Diogo Tomé Ramiro D.Almeida iBiMED-Institute of Biomedicine Department of Medical SciencesUniversity of AveiroAveiroPortugal CNC-center for Neuroscience and Cell biology University of CoimbraCoimbraPortugal

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate *** several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after ***,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

关键词： viable injury instru

Investigating loss of heterozygosity in a SCRaMbLEd yeast genome

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Science China(Life Sciences) 2019年第6期62卷 868-869页

作者： Junbiao Dai Shenzhen Key Laboratory of synthetic Genomics and center for synthetic Genomics Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

Loss of heterozygosity (LOH) is a phenomenon in which elimination of one parental genomic region occurs in interspecific hybrids. LOH is common in cancer (Deng et al., 1996;Koufos et al., 1985). However, genetic analy... 详细信息

关键词： Loss of heterozygosity elimination individual genomes

Inevitability or contingency: how many chromosomes do we really need?

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Science China(Life Sciences) 2019年第1期62卷 140-143页

作者： Shuangying Jiang Junbiao Dai Shenzhen Key Laboratory of synthetic Genomics and center for synthetic Genomics Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences

In an essay written by the evolutionary biologist Theodosius Dobzhansky in 1973,he pointed out that "Nothing in biology Makes Sense Except in the Light of Evolution."An interesting phenomenon in biology is the presence of variable numbers of chromosomes in different *** several species,which possess multiple circular chromosomes or simply linear chromosomes (Baril et al. 1989;Suwanto and Kaplan,1989;Jumas-Bilak et al.,1998), most prokaryotes only possess one circular *** contrast,the genomes of eukaryotic species are usually packaged into linear chromosomes with numbers varying from one to hundreds (Crosland and Crozier,1986;Lukhtanov,2015).

关键词： Inevitability contingency evolutionary biologist

Diatom-inspired multiscale mineralization of patterned protein–polysaccharide complex structures

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National Science Review 2021年第8期8卷 186-197页

作者： Ke Li Yingfeng Li Xinyu Wang Mengkui Cui Bolin An Jiahua Pu Jintao Liu Boyang Zhang Guijun Ma Chao Zhong School of Physical Science and Technology Shanghai Tech University center for Materials synthetic biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences CAS Key Laboratory of Quantitative Engineering biology Shenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences

Marine diatoms construct their hierarchically ordered, three-dimensional(3D) external structures called frustules through precise biomineralization processes. Recapitulating the remarkable architectures and functions of diatom frustules in artificial materials is a major challenge that has important technological implications for hierarchically ordered composites. Here, we report the construction of highly ordered,mineralized composites based on fabrication of complex self-supporting porous structures—made of genetically engineered amyloid fusion proteins and the natural polysaccharide chitin—and performing in situ multiscale protein-mediated mineralization with diverse inorganic materials, including SiO2, TiO2and Ga2O3. Subsequently, using sugar cubes as templates, we demonstrate that 3D fabricated porous structures can become colonized by engineered bacteria and can be functionalized with highly photoreactive minerals,thereby enabling co-localization of the photocatalytic units with a bacteria-based hydrogenase reaction for a successful semi-solid artificial photosynthesis system for hydrogen evolution. Our study thus highlights the power of coupling genetically engineered proteins and polysaccharides with biofabrication techniques to generate hierarchically organized mineralized porous structures inspired by nature.

关键词： biomimetic mineralization patterned porous structure genetic engineering amyloid protein artificial photosynthesis

Dissecting PCNA function with a systematically designed mutant library in yeast

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Journal of Genetics and Genomics 2019年第6期46卷 301-313页

作者： Qingwen Jiang Weimin Zhang Chenghao Liu Yicong Lin Qingyu Wu Junbiao Dai center for synthetic and systems biology School of Life Sciences Tsinghua University Beijing 100084 China Shenzhen Key Laboratory of synthetic Genomics and center for synthetic Genomics Institute of Synthetic Biology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences Shenzhen 518055 China Department of biology. Brandeis University. Massachusetts 02454 USA

Proliferating cell nuclear antigen (PCNA), encoded by POL30 in Saccharomyces cerevisiae, is a key component of DNA metabolism. Here, a library consisting of 304 PCNA mutants was designed and constructed to probe the contribution of each residue to the biological function of PCNA. Five regions with elevated sen sitivity to DNA damaging reagents were identified using high-throughput phe no type screening. Using a series of genetic and biochemical analyses, we demonstrated that one particular mutant, K168A, has defects in the DNA damage tolerance (DDT) pathway by disrupting the interaction between PCNA and Rad5. Subsequent domain analysis showed that the PCNA-Rad5 interaction is a prerequisite for the function of Rad5 in DDT. Our study not only provides a resource in the form of a library of versatile mutants to study the functions of PCNA, but also reveals a key residue on PCNA (K168) which highlights the importance of the PCNA-Rad5 interaction in the template switching (TS) pathway.

关键词： Mutagenesis High-throughput DNA damage tolerance Template switching Genetic interaction

Experimental identification of a comb-shaped chaotic region in multiple parameter spaces simulated by the Hindmarsh–Rose neuron model

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Chinese Physics B 2014年第3期23卷 179-185页

作者：贾冰 center for Computational system biology School of Mathematical Science Fudan University

A comb-shaped chaotic region has been simulated in multiple two-dimensional parameter spaces using the Hindmarsh-Rose （HR） neuron model in many recent studies, which can interpret almost all of the previously simulated bifurcation processes with chaos in neural firing patterns. In the present paper, a comb-shaped chaotic region in a two- dimensional parameter space was reproduced, which presented different processes of period-adding bifurcations with chaos with changing one parameter and fixed the other parameter at different levels. In the biological experiments, different period-adding bifurcation scenarios with chaos by decreasing the extra-cellular calcium concentration were observed from some neural pacemakers at different levels of extra-cellular 4-aminopyridine concentration and from other pacemakers at different levels of extra-cellular caesium concentration. By using the nonlinear time series analysis method, the determin- istic dynamics of the experimental chaotic firings were investigated. The period-adding bifurcations with chaos observed in the experiments resembled those simulated in the comb-shaped chaotic region using the HR model. The experimental results show that period-adding bifurcations with chaos are preserved in different two-dimensional parameter spaces, which provides evidence of the existence of the comb-shaped chaotic region and a demonstration of the simulation results in dif- ferent two-dimensional parameter spaces in the HR neuron model. The results also present relationships between different firing patterns in two-dimensional parameter spaces.

关键词： chaos neural firing bifurcation Hindmarsh-Rose model

Synchronization transition of a coupled system composed of neurons with coexisting behaviors near a Hopf bifurcation

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Chinese Physics B 2014年第5期23卷 180-190页

作者：贾冰 center for Computational system biology School of Mathematical ScienceFudan University

The coexistence of a resting condition and period-1 firing near a subcritical Hopf bifurcation point, lying between the monostable resting condition and period-1 firing, is often observed in neurons of the central nervous systems. Near such a bifurcation point in the Morris-Lecar （ML） model, the attraction domain of the resting condition decreases while that of the coexisting period-1 firing increases as the bifurcation parameter value increases. With the increase of the coupling strength, and parameter and initial value dependent synchronization transition processes from non-synchronization to compete synchronization are simulated in two coupled ML neurons with coexisting behaviors： one neuron chosen as the resting condition and the other the coexisting period-1 firing. The complete synchronization is either a resting condition or period-1 firing dependent on the initial values of period-1 firing when the bifurcation parameter value is small or middle and is period- 1 firing when the parameter value is large. As the bifurcation parameter value increases, the probability of the initial values of a period- 1 firing neuron that lead to complete synchronization of period- 1 firing increases, while that leading to complete synchronization of the resting condition decreases. It shows that the attraction domain of a coexisting behavior is larger, the probability of initial values leading to complete synchronization of this behavior is higher. The bifurcations of the coupled system are investigated and discussed. The results reveal the complex dynamics of synchronization behaviors of the coupled system composed of neurons with the coexisting resting condition and period-1 firing, and are helpful to further identify the dynamics of the spatiotemporal behaviors of the central nervous system.

关键词： synchronization neuronal network Hopf bifurcation coexistence

Metabolic reprogramming: a new option for the treatment of spinal cord injury

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Neural Regeneration Research 2025年第4期20卷 1042-1057页

作者： Jiangjie Chen Jinyang Chen Chao Yu Kaishun Xia Biao Yang Ronghao Wang Yi Li Kesi Shi Yuang Zhang Haibin Xu Xuesong Zhang Jingkai Wang Qixin Chen Chengzhen Liang Department of Orthopedics The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Orthopedics Research Institute of Zhejiang University Zhejiang UniversityHangzhouZhejiang ProvinceChina Key Laboratory of Motor system Disease Research and Precision Therapy of Zhejiang Province HangzhouZhejiang ProvinceChina Clinical Research center of Motor system Disease of Zhejiang Province HangzhouZhejiang ProvinceChina Qiandongnan Prefecture People’s Hospital KailiGuizhou ProvinceChina Department of Orthopedics Fourth Medical CenterChinese PLA General HospitalBeijingChina

Spinal cord injuries impose a notably economic burden on society,mainly because of the severe after-effects they *** the ongoing development of various therapies for spinal cord injuries,their effectiveness remains ***,a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic *** this review,we explore the metabolic changes that occur during spinal cord injuries,their consequences,and the therapeutic tools available for metabolic *** spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic ***,spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism,lipid metabolism,and mitochondrial *** metabolic disturbances lead to corresponding pathological changes,including the failure of axonal regeneration,the accumulation of scarring,and the activation of *** rescue spinal cord injury at the metabolic level,potential metabolic reprogramming approaches have emerged,including replenishing metabolic substrates,reconstituting metabolic couplings,and targeting mitochondrial therapies to alter cell *** available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord *** further advance the metabolic treatment of the spinal cord injury,future efforts should focus on a deeper understanding of neurometabolism,the development of more advanced metabolomics technologies,and the design of highly effective metabolic interventions.

关键词： axons glycolysis metabolic reprogramming metabolism mitochondria neural regeneration neuroprotection oxidative phosphorylation spinal cord injury therapy

A novel CRISPR/Cas9 system with high genomic editing efficiency and recyclable auxotrophic selective marker for multiple-step metabolic rewriting in Pichia pastoris

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synthetic and systems Biotechnology 2023年第3期8卷 445-451页

作者： Xiang Wang Yi Li Zhehao Jin Xiangjian Liu Xiang Gao Shuyuan Guo Tao Yu center for synthetic Biochemistry CAS Key Laboratory of Quantitative Engineering BiologyShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences(CAS)Shenzhen518055China University of the Chinese Academy of Sciences Beijing100049China center for Materials synthetic biology CAS Key Laboratory of Quantitative Engineering Biology of CASShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academic of ScienceShenzhen518055China

The methylotrophic budding yeast Pichia pastoris has been utilized to the production of a variety of heterologous recombinant proteins owing to the strong inducible alcohol oxidase promoter(pAOX1).However,it is difficult to use *** as the chassis cell factory for high-valuable metabolite biosynthesis due to the low homologous recombination(HR)efficiency and the limitation of handy selective markers,especially in the condition of multistep biosynthetic ***,we developed a novel CRISPR/Cas9 system with highly editing efficiencies and recyclable auxotrophic selective marker(HiEE-ReSM)to facilitate cell factory in ***,we improved the HR rates of *** through knocking out the non-homologous-end-joining gene(Δku70)and overexpressing HR-related proteins(RAD52 and RAD59),resulting in higher positive rate compared to the basal strain,achieved 97%.Then,we used the uracil biosynthetic genes PpURA3 as the reverse screening marker,which can improve the recycling efficiency of ***,the HR rate is still 100%in uracil auxotrophic ***,we improved the growth rate of uracil auxotrophic yeast strains by overexpressing the uracil transporter(scFUR4)to increase the uptake of exogenous uracil from ***,we explored the optimal concentration of uracil(90 mg/L)for strain *** the end,the HiEE-ReSM system has been applied for the inositol production(250 mg/L)derived from methanol in *** systems will contribute to *** as an attractive cell factory for the complex compound biosynthesis through multistep metabolic pathway engineering and will be a useful tool to improve one carbon(C1)bio-utilization.

关键词： Pichia pastoris Uracil auxotroph CRISPR/Cas9 Recyclable selective marker Homology directed repair