Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse form...Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.展开更多
Efforts have been conducted on cyanobacterial genome editing,yet achieving genome editing in cyanophages remains challenging.Editing cyanophage genomes is crucial for understanding and manipulating their in-teractions...Efforts have been conducted on cyanobacterial genome editing,yet achieving genome editing in cyanophages remains challenging.Editing cyanophage genomes is crucial for understanding and manipulating their in-teractions with cyanobacterial hosts,offering potential solutions for controlling cyanobacterial blooms.In this study,we developed a streamlined CRISPR-Cas12a-based method for efficient cyanophage genome editing and then applied this method to the cyanophages A-1(L)and A-4(L)of Anabeana sp.PCC.7120.Multiple hypothetical genes were edited and knocked out from these two cyanophage genomes,generating viable mutants with varying capabilities to inhibit cyanobacterial growth.All these mutants displayed significant inhibitory effects on the host,indicating that these genes were non-essential for phage life cycle and the deletion led to little impairment of the cyanophages in infectious efficiency to their host.By iterative and simultaneous gene knockouts in cya-nophage A-4(L),we achieved the minimal genome mutant with a 2400 bp reduction in genome size,representing a 5.75%decrease compared to the wild type(WT).In conclusion,these cyanophage mutants can facilitate the identification of nonessential genes for cyanophages biology and the insertion of foreign genes for synthetic biology research.This advancement holds promise in addressing the widespread issue of water blooms and the associated environmental hazards.展开更多
Predicting potential lncRNA-disease association pairs is an important issue in the field of biomedicine.Traditional lncRNA-disease association prediction algorithms are mainly based on biological network models.For in...Predicting potential lncRNA-disease association pairs is an important issue in the field of biomedicine.Traditional lncRNA-disease association prediction algorithms are mainly based on biological network models.For instance,RWRlncD is developed for predicting the potential lncRNA-disease association by performing random walk with restart on lncRNA functionally similar networks(Sun et al.,2014).However,biological graph network algorithms often have certain limitations and low accuracy.With the development of machine learning,new ideas have been brought to the construction of the association prediction algorithm(Liu et al.,2016,2019a,b;Wan et al.,2019).展开更多
Nanomaterials with various dimensionalities(e.g.,nanowires,nanofilms,two-dimensional materials,and three-dimensional nanostructures)have shown great potential in the recent development of flexible electronics.Conventi...Nanomaterials with various dimensionalities(e.g.,nanowires,nanofilms,two-dimensional materials,and three-dimensional nanostructures)have shown great potential in the recent development of flexible electronics.Conventionally,organic solvents are inevitable while integrating nanomaterials onto flexible substrates,where polymer mediator-assisted transfer techniques are involved.This often damages the flexible substrate and thus hamper the large-scale application of nanomaterials.Here we report a method using watersoluble sugar as a mediator to facilely transfer nanomaterials onto rigid or flexible substrates.This method requires no organic solvent during transfer.More importantly,the morphology and properties of transferred nanomaterials,such as shape,microstructure,resistivity,and transmittance are well preserved on the target substrate.We believe that this universal and rapid transfer method can greatly advance the applications of nanomaterials in the field of flexible devices and beyond.展开更多
基金supported by research grants from the National Natural Science Foundation of China(31671510 and 31871461 to H.H.31771592 to W.X.)。
文摘Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.
基金supported by the Ministry of Science and Technology of China,National Key R&D Program of China(http://www.most.gov.cngrant no.2018YFA0903100).
文摘Efforts have been conducted on cyanobacterial genome editing,yet achieving genome editing in cyanophages remains challenging.Editing cyanophage genomes is crucial for understanding and manipulating their in-teractions with cyanobacterial hosts,offering potential solutions for controlling cyanobacterial blooms.In this study,we developed a streamlined CRISPR-Cas12a-based method for efficient cyanophage genome editing and then applied this method to the cyanophages A-1(L)and A-4(L)of Anabeana sp.PCC.7120.Multiple hypothetical genes were edited and knocked out from these two cyanophage genomes,generating viable mutants with varying capabilities to inhibit cyanobacterial growth.All these mutants displayed significant inhibitory effects on the host,indicating that these genes were non-essential for phage life cycle and the deletion led to little impairment of the cyanophages in infectious efficiency to their host.By iterative and simultaneous gene knockouts in cya-nophage A-4(L),we achieved the minimal genome mutant with a 2400 bp reduction in genome size,representing a 5.75%decrease compared to the wild type(WT).In conclusion,these cyanophage mutants can facilitate the identification of nonessential genes for cyanophages biology and the insertion of foreign genes for synthetic biology research.This advancement holds promise in addressing the widespread issue of water blooms and the associated environmental hazards.
基金Supplementary material is available at Journal of Molecular Cell Biology online.This research was supported by the Key Projects of National Natural Science Foundation of China(11831015)the Major Research Plan of National Natural Science Foundation of China(91730301)Postgraduate Research&Practice Innovation Program of Jiangnan University(JNKY19_051).
文摘Predicting potential lncRNA-disease association pairs is an important issue in the field of biomedicine.Traditional lncRNA-disease association prediction algorithms are mainly based on biological network models.For instance,RWRlncD is developed for predicting the potential lncRNA-disease association by performing random walk with restart on lncRNA functionally similar networks(Sun et al.,2014).However,biological graph network algorithms often have certain limitations and low accuracy.With the development of machine learning,new ideas have been brought to the construction of the association prediction algorithm(Liu et al.,2016,2019a,b;Wan et al.,2019).
基金financially supported by the funds of the“Science Technology and Innovation Committee of Shenzhen Municipality”(grant No.JCYJ20160613160524999 and JCYJ20170817111714314)“Guangdong Innovative and Entrepreneurial Research Team Program”under contract No.2016ZT06G587+1 种基金the National Natural Science Foundation of China(No.51771089 and U1613204)the Key-Area Research and Development Program of Guangdong Province(No.2019B010931001).
文摘Nanomaterials with various dimensionalities(e.g.,nanowires,nanofilms,two-dimensional materials,and three-dimensional nanostructures)have shown great potential in the recent development of flexible electronics.Conventionally,organic solvents are inevitable while integrating nanomaterials onto flexible substrates,where polymer mediator-assisted transfer techniques are involved.This often damages the flexible substrate and thus hamper the large-scale application of nanomaterials.Here we report a method using watersoluble sugar as a mediator to facilely transfer nanomaterials onto rigid or flexible substrates.This method requires no organic solvent during transfer.More importantly,the morphology and properties of transferred nanomaterials,such as shape,microstructure,resistivity,and transmittance are well preserved on the target substrate.We believe that this universal and rapid transfer method can greatly advance the applications of nanomaterials in the field of flexible devices and beyond.
