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Simple and robust 3D MINFLUX excitation with a variable phase plate

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Light(Science & Applications) 2024年第7期13卷 1354-1363页

作者： Takahiro Deguchi Jonas Ries European molecular biology laboratory Cell Biology and BiophysicsHeidelbergGermany. Max Perutz Labs Vienna Biocenter Campus(VBC)ViennaAustria. University of Vienna Center for Molecular BiologyDepartment of Structural and Computational BiologyViennaAustria. University of Vienna Faculty of PhysicsViennaAustria

MINFLUX has achieved extraordinary resolution in superresolution imaging and single fluorophore *** is based on localizing single fluorophores by rapid probing with a patterned beam that features a local intensity *** implementations,however,are complex and expensive and are limited in speed and ***,we show that a combination of an electro-optical modulator with a segmented birefringent element such as a spatial light modulator produces a variable phase plate for which the phase can be scanned on the MHz *** or top-hat phase patterns generate high-contrast compact excitation point-spread functions for MINFLUX localization in the x,y,and z-direction,respectively,which can be scanned across a fluorophore within a microsecond,switched within 60 microseconds and alternated among different excitation *** discuss how to compensate for non-optimal performance of the components and present a robust 3D and multi-color MINFLUX excitation module,which we envision as an integral component of a high-performance and cost-effective open-source MINFLUX.

关键词： excitation phase switched

Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

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Journal of Integrative Plant biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key laboratory of molecular and cellular biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis

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Brain-inspired chaotic spiking backpropagation

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National Science Review 2024年第6期11卷 169-179页

作者： Zijian Wang Peng Tao Luonan Chen Key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of Sciences Key laboratory of Systems biology Shanghai Institute of Biochemistry and Cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences Guangdong Institute of Intelligence Science and Technology Pazhou laboratory(Huangpu)

Spiking neural networks(SNNs) have superior energy efficiency due to their spiking signal transmission,which mimics biological nervous systems, but they are difficult to train effectively. Although surrogate gradient-based methods offer a workable solution, trained SNNs frequently fall into local minima because they are still primarily based on gradient dynamics. Inspired by the chaotic dynamics in animal brain learning, we propose a chaotic spiking backpropagation(CSBP) method that introduces a loss function to generate brain-like chaotic dynamics and further takes advantage of the ergodic and pseudo-random nature to make SNN learning effective and robust. From a computational viewpoint, we found that CSBP significantly outperforms current state-of-the-art methods on both neuromorphic data sets(***-CIFAR10 and DVS-Gesture) and large-scale static data sets(e.g. CIFAR100 and Image Net) in terms of accuracy and robustness. From a theoretical viewpoint, we show that the learning process of CSBP is initially chaotic, then subject to various bifurcations and eventually converges to gradient dynamics,consistently with the observation of animal brain activity. Our work provides a superior core tool for direct SNN training and offers new insights into understanding the learning process of a biological brain.

关键词： spiking neural networks surrogate gradient local minima backpropagation brain-inspired learning chaos

Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental *** a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and *** gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ *** maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)*** addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization *** conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

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Journal of Integrative Plant biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming Zhao Jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin Pengcheng Yin Chunjiang Zhou Geng Wang Ministry of Education Key laboratory of molecular and cellular biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental AdaptationHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China College of Chemical Engineering Shijiazhuang UniversityShijiazhuang 050035China Institute of Botany Chinese Academy of SciencesBeijing 100093China

Most mechanistic details of chronologically ordered regulation of leaf senescence are *** networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related ***,AtWRKY53binds to its own promoter and represses transcription of AtWRKY53,but the biological significance and mechanism underlying this selfrepression remain *** this study,we identified the VQ motif-containing protein AtVQ25as a cooperator of *** expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf ***25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence,***,we identified AtWRKY53 as an interacting partner of *** determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of *** addition,our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA)*** leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant,atsid2,and Nah G transgenic plants;AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf ***,we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins

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Exploring noncoding variants in genetic diseases:from detection to functional insights

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Journal of Genetics and Genomics 2024年第2期51卷 111-132页

作者： Ke Wu Fengxiao Bu Yang Wu Gen Zhang Xin Wang Shunmin He Mo-Fang Liu Runsheng Chen Huijun Yuan Institute of Rare Diseases West China Hospital of Sichuan UniversityChengduSichuan 610041China Key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China Key laboratory of RNA biology Center for Big Data Research in HealthInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key laboratory of molecular biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

关键词： Noncoding variation Genetic disease Research approach Challenge

Octopamine enhances learning

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National Science Review 2024年第6期11卷 82-83页

作者： Yvette E.Fisher Department of molecular and cell biology and Helen Wills Neuroscience Institute University of California

Across the animal kingdom, diverse monoamines actuate and modulate neural circuit function. However, measuring the rapid dynamics of these neuromodulators at cellular resolution has historically presented significant ... 详细信息

关键词： DOPAMINE TYRAMINE FLIES

Intracellular redox potential-driven live-cell synthesis of CdSe quantum dots in Staphylococcus aureus

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Science China Chemistry 2024年第3期67卷 990-999页

作者： Cai-Qin Wu An-An Liu Xu Li Jia-Wei Tu Juan Kong Ling-Ling Yang Jian-Hong Jia Chuan Wang Bin Hu Zhi-Xiong Xie Dai-Wen Pang The Institute for Advanced Studies College of Chemistry and Molecular SciencesCollege of Life SciencesHubei Key Laboratory of Cell HomeostasisWuhan UniversityWuhan 430072China Research Center for Analytical Sciences College of ChemistryState Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Biosensing and Molecular RecognitionFrontiers Science Center for New Organic MatterFrontiers Science Center for Cell Responsesand Haihe Laboratory of Sustainable Chemical TransformationsNankai UniversityTianjin 300071China

Biosynthesized semiconductor quantum dots(QDs) have bright fluorescence,adjustable particle sizes,and environmental friendliness,endowing them with convenience and potential for biological *** to the unclear mechanism of the cellular environment on the live-cell synthesis of QDs,it is still difficult to regulate their optical ***,the critical role of the intracellular redox environment in regulating the fluorescence properties of biosynthesized CdSe QDs in Staphylococcus aureus(***) has been *** glutathione peroxidase(GPx) activity directly affects the intracellular H_(2)O_(2) produced in the SeO_(3)^(2-) reduction,which further manipulates the glutathione redox cycle to determine the content of low-valence *** a result,the fluorescence intensity of the synthesized CdSe QDs increases by 60% in the GPx overexpressed *** cellular redox potential that is controlled by the GSH redox cycle provides the driving force for the reduction of SeO_(3)^(2-),facilitating the synthesis of CdSe QDs in *** *** proposed mechanism of the cellular redox state provides a new perspective for regulating the synthesis of semiconductor nanomaterials in live cells.

关键词： redox H_(2)O_(2) peroxidase quantum dot Staphylococcus aureus

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Pathologically relevant aldoses and environmental aldehydes cause cilium disassembly via formyl group-mediated mechanisms

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Journal of molecular cell biology 2024年第1期16卷 15-28页

作者： Te Li Min Liu Fan Yu Song Yang Weiwen Bu Kai Liu Jia Yang Hua Ni Mulin Yang Hanxiao Yin Renjie Hong Dengwen Li Huĳie Zhao Jun Zhou Haihe laboratory of cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Protein ScienceCollege of Life SciencesNankai UniversityTianjin 300071China laboratory of Tissue Homeostasis Haihe Laboratory of Cell EcosystemTianjin 300462China Center for cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongShandong Provincial Key Laboratory of Animal Resistance BiologyCollege of Life SciencesShandong Normal UniversityJinan 250014China

Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan ***,the mechanistic link of cilia to CMD complications is still poorly ***,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar ***,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl *** studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium *** vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm *** findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.

关键词： carbohydrate metabolism disorder aldose aldehyde cilium disassembly formyl group calcium influx HDAC6