The PML gene is involved in the t（15;17） translocation of acute promyelocytic leukaemia （APL）, which generates the oncogenic fusion protein PML （promyelocytic leukaemia protein）-retinoic acid receptor alpha. The...The PML gene is involved in the t（15;17） translocation of acute promyelocytic leukaemia （APL）, which generates the oncogenic fusion protein PML （promyelocytic leukaemia protein）-retinoic acid receptor alpha. The PML protein localises to a subnuclear structure called the PML nuclear domain （PML-ND）, of which PML is the essential structural component. In APL, PML-NDs are disrupted, thus implicating these structures in the pathogenesis of this leukaemia. Unexpectedly, recent studies indicate that PML and the PML-ND play a tumour suppressive role in several different types of human neoplasms in addition to APL. Because of PML＇s extreme versatility and involvement in multiple cellular pathways, understanding the mechanisms underlying its function, and therefore role in tumour suppression, has been a challenging task. In this review, we attempt to critically appraise the more recent advances in this field and propose new avenues of investigation.展开更多
One of the strategies of treating Parkinson's disease(PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells.Potential sources for cells range from autologous grafts of dop...One of the strategies of treating Parkinson's disease(PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells.Potential sources for cells range from autologous grafts of dopamine secreting cells,fetal ventral mesencephalon tissue,to various stem cell types.Over the past quarter century,many experimental replacement therapies have been tried on PD animal models as well as human patients,yet none resulted in satisfactory outcomes that warrant wide applications.Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells(ntES) or induced pluripotent stem cells(iPS) derived cells can be used to successfully treat rodent PD models,thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PD.Meanwhile,however,post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area,indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain.A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson's disease.It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.展开更多
In Arabidopsis, the phytohormone abscisic acid （ABA） plays a vital role in inhibiting seed germination and in postgermination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcript...In Arabidopsis, the phytohormone abscisic acid （ABA） plays a vital role in inhibiting seed germination and in postgermination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, along with AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI （CRWN） proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA-controlled seed germination by regulating the degradation of ABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstream of ABIS. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degrada- tion in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination.展开更多
Recent progress in understanding higher-order chromatin organization in the nucleus has been considerable. From single gene to chromosome territory, realistic biophysical models can now accurately predict some of the ...Recent progress in understanding higher-order chromatin organization in the nucleus has been considerable. From single gene to chromosome territory, realistic biophysical models can now accurately predict some of the structural feature of cell nuclei. Despite growing evidence of a deterministic nuclear organization, the physiological consequence of spatial genome organization is still unclear. In the simple eukaryotic model, Saccharomyces cerevisiae, clear correlation between gene position and transcription has been established. In this review, we will focus on higher-order chromatin organization in yeast with respect to the nuclear envelope and nucleolus. In Arabidopsis thaliana, a model plant for which we have a complete genome sequence, chromosome territory （CT） arrangement and somatic homologous pairing in interphase nuclei seem to occur randomly. Since chromosomes containing nucleolar organizer regions associate more frequently to form a single nucleolar structure, as in yeast, the nucleolus seems to play a major role in organizing nuclear space. Recent findings have begun to elucidate how plant regulatory factors, such as chromatin remodeling or histone chaperones, affect the chromatin state of ribosomal DNA genes located in two distinct CTarrangements in the nucleus. The functional outcome of yeast nuclear organization allowed us to propose how nuclear organization might contribute to a novel type of epigenetic regulation： the spatial regulation of transcription.展开更多
In order to research whether it is suitable to set a geological disposal repository for high-level radioactive nuclear waste into one target granite body,two active source seismic profles were arranged near a small to...In order to research whether it is suitable to set a geological disposal repository for high-level radioactive nuclear waste into one target granite body,two active source seismic profles were arranged near a small town named Tamusu,Western China.The study area is with complex surface conditions,thus the seismic exploration encountered a variettraveltimey of technical difculties such as crossing obstacles,de-noising harmful scattered waves,and building complex near-surface velocity models.In order to address those problems,techniques including cross-obstacle seismic geometry design,angle-domain harmful scattered noise removal,and an acoustic wave equation-based inversion method jointly utilizing both the and waveform of frst arrival waves were adopted.The fnal seismic images clearly exhibit the target rock’s unconformable contact boundary and its top interface beneath the sedimentary and weathered layers.On this basis,it could be confrmed that the target rock is not thin or has been transported by geological process from somewhere else,but a native and massive rock.There are a few small size fractures whose space distribution could be revealed by seismic images within the rock.The fractures should be kept away.Based on current research,it could be considered that active source seismic exploration is demanded during the sitting process of the geological disposal repository for nuclear waste.The seismic acquisition and processing techniques proposed in the present paper would ofer a good reference value for similar researches in the future.展开更多
A novel variational wave function defined as a Jastrow factor multiplying a backflow transformed Slater determinant was developed for A=3 nuclei.The Jastrow factor and backflow transformation were represented by artif...A novel variational wave function defined as a Jastrow factor multiplying a backflow transformed Slater determinant was developed for A=3 nuclei.The Jastrow factor and backflow transformation were represented by artificial neural networks.With this newly developed wave function,variational Monte Carlo calculations were carried out for3H and3He nuclei starting from a nuclear Hamiltonian based on the leadingorder pionless effective field theory.The obtained ground-state energy and charge radii were successfully benchmarked against the results of the highly-accurate hypersphericalharmonics method.The backflow transformation plays a crucial role in improving the nodal surface of the Slater determinant and,thus,providing accurate ground-state energy.展开更多
Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules,which is like the luminescence mechanism of AIE molecules.However,in comparison to AIE molecules,the...Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules,which is like the luminescence mechanism of AIE molecules.However,in comparison to AIE molecules,the aggregation of biological elements appears to be more complex due to membership and mechanism,which is in line with the trend in biological evolution following the principle of simplicity to complexity.Here,we chose three distinctive examples because they differ significantly in their composition and show a progression from simple to complex,namely protein–protein complexes,protein–nucleic acid complexes,and protein–nucleic acid–lipid complexes.The majority of units that perform functions within cells belong to these three types.We discuss the formation mechanisms and related functions of the protein–protein complex(PML-NB),the proteins–nucleic acids complex ribosome,and the proteins–nucleic acids–lipids complex exosome,and hope to provide expert insight for related fields.展开更多
PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramer...PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly.The productive RBCC oligomerization allows subsequent PML biogenesis steps,including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions.In promyelocytic leukemia,the oncoprotein PML/RARa(P/R)inhibits PML NBs assembly and leads to a full-fledged leukemogenesis.In this review,we review the recent progress in PML and acute promyelocytic leukemia fields,highlighting the protein oligomerization as an important direction of future targeted therapy.展开更多
文摘The PML gene is involved in the t（15;17） translocation of acute promyelocytic leukaemia （APL）, which generates the oncogenic fusion protein PML （promyelocytic leukaemia protein）-retinoic acid receptor alpha. The PML protein localises to a subnuclear structure called the PML nuclear domain （PML-ND）, of which PML is the essential structural component. In APL, PML-NDs are disrupted, thus implicating these structures in the pathogenesis of this leukaemia. Unexpectedly, recent studies indicate that PML and the PML-ND play a tumour suppressive role in several different types of human neoplasms in addition to APL. Because of PML＇s extreme versatility and involvement in multiple cellular pathways, understanding the mechanisms underlying its function, and therefore role in tumour suppression, has been a challenging task. In this review, we attempt to critically appraise the more recent advances in this field and propose new avenues of investigation.
基金Support by the National Key Basic Research and Development Program of China (Grant No. 2006CB0F0603)Science and Technology Plan, Beijing Municipal Science &Technology Commission (Grant No. H020220010290)
文摘One of the strategies of treating Parkinson's disease(PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells.Potential sources for cells range from autologous grafts of dopamine secreting cells,fetal ventral mesencephalon tissue,to various stem cell types.Over the past quarter century,many experimental replacement therapies have been tried on PD animal models as well as human patients,yet none resulted in satisfactory outcomes that warrant wide applications.Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells(ntES) or induced pluripotent stem cells(iPS) derived cells can be used to successfully treat rodent PD models,thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PD.Meanwhile,however,post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area,indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain.A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson's disease.It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.
基金supported by grants from the National Natural Science Foundation(31100211)the Ministry of Science and Technology of China(2014CB943402)
文摘In Arabidopsis, the phytohormone abscisic acid （ABA） plays a vital role in inhibiting seed germination and in postgermination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, along with AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI （CRWN） proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA-controlled seed germination by regulating the degradation of ABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstream of ABIS. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degrada- tion in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination.
文摘Recent progress in understanding higher-order chromatin organization in the nucleus has been considerable. From single gene to chromosome territory, realistic biophysical models can now accurately predict some of the structural feature of cell nuclei. Despite growing evidence of a deterministic nuclear organization, the physiological consequence of spatial genome organization is still unclear. In the simple eukaryotic model, Saccharomyces cerevisiae, clear correlation between gene position and transcription has been established. In this review, we will focus on higher-order chromatin organization in yeast with respect to the nuclear envelope and nucleolus. In Arabidopsis thaliana, a model plant for which we have a complete genome sequence, chromosome territory （CT） arrangement and somatic homologous pairing in interphase nuclei seem to occur randomly. Since chromosomes containing nucleolar organizer regions associate more frequently to form a single nucleolar structure, as in yeast, the nucleolus seems to play a major role in organizing nuclear space. Recent findings have begun to elucidate how plant regulatory factors, such as chromatin remodeling or histone chaperones, affect the chromatin state of ribosomal DNA genes located in two distinct CTarrangements in the nucleus. The functional outcome of yeast nuclear organization allowed us to propose how nuclear organization might contribute to a novel type of epigenetic regulation： the spatial regulation of transcription.
基金This research was supported by the National Key R&D Program of China(No.2018YFC1503200)the Nuclear Waste Geological Disposal Project([2013]727)+2 种基金the National Natural Science Foundation of China(Grant Nos.41790463 and 41730425)the Spark Program of Earthquake Sciences of CEA(XH18063Y)the Special Fund of GEC of CEA(YFGEC2017003,SFGEC2014006).
文摘In order to research whether it is suitable to set a geological disposal repository for high-level radioactive nuclear waste into one target granite body,two active source seismic profles were arranged near a small town named Tamusu,Western China.The study area is with complex surface conditions,thus the seismic exploration encountered a variettraveltimey of technical difculties such as crossing obstacles,de-noising harmful scattered waves,and building complex near-surface velocity models.In order to address those problems,techniques including cross-obstacle seismic geometry design,angle-domain harmful scattered noise removal,and an acoustic wave equation-based inversion method jointly utilizing both the and waveform of frst arrival waves were adopted.The fnal seismic images clearly exhibit the target rock’s unconformable contact boundary and its top interface beneath the sedimentary and weathered layers.On this basis,it could be confrmed that the target rock is not thin or has been transported by geological process from somewhere else,but a native and massive rock.There are a few small size fractures whose space distribution could be revealed by seismic images within the rock.The fractures should be kept away.Based on current research,it could be considered that active source seismic exploration is demanded during the sitting process of the geological disposal repository for nuclear waste.The seismic acquisition and processing techniques proposed in the present paper would ofer a good reference value for similar researches in the future.
基金Supported by National Key R&D Program of China (018YFA0404400)National Natural Science Foundation of China (12070131001,11875075,11935003,11975031,12141501)。
文摘A novel variational wave function defined as a Jastrow factor multiplying a backflow transformed Slater determinant was developed for A=3 nuclei.The Jastrow factor and backflow transformation were represented by artificial neural networks.With this newly developed wave function,variational Monte Carlo calculations were carried out for3H and3He nuclei starting from a nuclear Hamiltonian based on the leadingorder pionless effective field theory.The obtained ground-state energy and charge radii were successfully benchmarked against the results of the highly-accurate hypersphericalharmonics method.The backflow transformation plays a crucial role in improving the nodal surface of the Slater determinant and,thus,providing accurate ground-state energy.
基金National Natural Science Foundation of China (NSFC)Key Projects,Grant/Award Numbers:31630027,32030060NSFC International Collaboration Key Project,Grant/Award Number:51861135103+5 种基金NSFC-German Research Foundation (DFG),Grant/Award Number:31761133013China Postdoctoral Science Foundation,Grant/Award Number:2020M680478the Beijing-Tianjin-Hebei Basic Research Cooperation Project,Grant/Award Number:19JCZDJC64100Ten Thousand Elite Plan,Grant/Award Number:Y9E21Z11CAS international collaboration plan,Grant/Award Number:E0632911ZXNational KeyResearch&Development Program of China,Grant/Award Number:2018YFE0117800。
文摘Most cellular elements could be functioned by forming aggregate structures through interactions with other molecules,which is like the luminescence mechanism of AIE molecules.However,in comparison to AIE molecules,the aggregation of biological elements appears to be more complex due to membership and mechanism,which is in line with the trend in biological evolution following the principle of simplicity to complexity.Here,we chose three distinctive examples because they differ significantly in their composition and show a progression from simple to complex,namely protein–protein complexes,protein–nucleic acid complexes,and protein–nucleic acid–lipid complexes.The majority of units that perform functions within cells belong to these three types.We discuss the formation mechanisms and related functions of the protein–protein complex(PML-NB),the proteins–nucleic acids complex ribosome,and the proteins–nucleic acids–lipids complex exosome,and hope to provide expert insight for related fields.
基金supported by research grants 81970132,81770142,81370620,81570120,31070645,81800144,and 31800642 from National Natural Science Foundation of Chinaa research grant 20152504 from Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support+4 种基金The Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institute of Higher Learninga research grant 11JC1407200 from SMSTCa research grant 12ZZ109 from SMEProgram for New Century Excellent Talents in University(NCET-10–9571)Samuel Waxman Cancer Research Foundation.
文摘PML nuclear bodies(NBs),which are increasingly recognized as the central hub of many cellular signaling events,are superassembled spherical complexes with diameters of 0.1–2mm.Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly.The productive RBCC oligomerization allows subsequent PML biogenesis steps,including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions.In promyelocytic leukemia,the oncoprotein PML/RARa(P/R)inhibits PML NBs assembly and leads to a full-fledged leukemogenesis.In this review,we review the recent progress in PML and acute promyelocytic leukemia fields,highlighting the protein oligomerization as an important direction of future targeted therapy.
