Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. The...Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an unquestioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed.展开更多
Rapid climate change has led to enhanced soil salinity,one of the major determinants of land degradation,resulting in low agricultural productivity.This has a strong negative impact on food security and environmental ...Rapid climate change has led to enhanced soil salinity,one of the major determinants of land degradation,resulting in low agricultural productivity.This has a strong negative impact on food security and environmental sustainability.Plants display various physiological,developmental,and cellular responses to deal with salt stress.Recent studies have highlighted the root cap as the primary stress sensor and revealed its crucial role in halotropism.The root cap covers the primary root meristem and is the first cell type to sense and respond to soil salinity,relaying the signal to neighboring cell types.However,it remains unclear how root-cap cells perceive salt stress and contribute to the salt-stress response.Here,we performed a root-cap cell-specific proteomics study to identify changes in the proteome caused by salt stress.The study revealed a very specific salt-stress response pattern in root-cap cells compared with non-rootcap cells and identified several novel proteins unique to the root cap.Root-cap-specific protein–protein interaction(PPI)networks derived by superimposing proteomics data onto known global PPI networks revealed that the endoplasmic reticulum(ER)stress pathway is specifically activated in root-cap cells upon salt stress.Importantly,we identified root-cap-specific jacalin-associated lectins(JALs)expressed in response to salt stress.A JAL10-GFP fusion protein was shown to be localized to the ER.Analysis of jal10 mutants indicated a role for JAL10 in regulating the ER stress pathway in response to salt.Taken together,our findings highlight the participation of specific root-cap proteins in salt-stress response pathways.Furthermore,root-cap-specific JAL proteins and their role in the salt-mediated ER stress pathway open a new avenue for exploring tolerance mechanisms and devising better strategies to increase plant salinity tolerance and enhance agricultural productivity.展开更多
BACKGROUND Retinal organoids serve as excellent human-specific disease models for conditions affecting otherwise inaccessible retinal tissue from patients.They permit the isolation of key cell types affected in variou...BACKGROUND Retinal organoids serve as excellent human-specific disease models for conditions affecting otherwise inaccessible retinal tissue from patients.They permit the isolation of key cell types affected in various eye diseases including retinal ganglion cells(RGCs)and Müller glia.AIM To refine human-induced pluripotent stem cells(hiPSCs)differentiated into threedimensional(3D)retinal organoids to generate sufficient numbers of RGCs and Müller glia progenitors for downstream analyses.METHODS In this study we described,evaluated,and refined methods with which to generate Müller glia and RGC progenitors,isolated them via magnetic-activated cell sorting,and assessed their lineage stability after prolonged 2D culture.Putative progenitor populations were characterized via quantitative PCR and immunocytochemistry,and the ultrastructural composition of retinal organoid cells was investigated.RESULTS Our study confirms the feasibility of generating marker-characterized Müller glia and RGC progenitors within retinal organoids.Such retinal organoids can be dissociated and the Müller glia and RGC progenitor-like cells isolated via magnetic-activated cell sorting and propagated as monolayers.CONCLUSION Enrichment of Müller glia and RGC progenitors from retinal organoids is a feasible method with which to study cell type-specific disease phenotypes and to potentially generate specific retinal populations for cell replacement therapies.展开更多
During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 h...During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, “the dirtiest place in the cell” in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.展开更多
The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous huma...The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved.One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.展开更多
The cell-type continuous electromagnetic radiation system is a demonstration device capable of generating high-power millimeter electromagnetic waves of a specific wavelength and observing their effects on living orga...The cell-type continuous electromagnetic radiation system is a demonstration device capable of generating high-power millimeter electromagnetic waves of a specific wavelength and observing their effects on living organisms.It irradiates a biological sample placed in a 30×30×50 cm^(3)cell with electromagnetic waves in the 3.15-mm-wavelength region(with an output of≥1 W)and analyzes the temperature change of the sample.A vacuum electronic device-based coupled-cavity backward-wave oscillator converts the electron energy of the electron beam into radiofrequency(RF)energy and radiates it to the target through an antenna,increasing the temperature through the absorption of RF energy in the skin.The system causes pain and ultimately reduces combat power.A cell-type continuous electromagnetic radiation system consisting of four parts—an electromagnetic-wave generator,a highvoltage power supply,a test cell,and a system controller—generates an RF signal of≥1 W in a continuous waveform at a 95-GHz center frequency,as well as a chemical solution with a dielectric constant similar to that of the skin of a living organism.An increase of 5°C lasting approximately 10 s was confirmed through an experiment.展开更多
Background:Single-cell RNA sequencing(scRNA-seq)technology is now becoming a widely applied method of transcriptome exploration that helps to reveal cell-type composition as well as cell-state heterogeneity for specif...Background:Single-cell RNA sequencing(scRNA-seq)technology is now becoming a widely applied method of transcriptome exploration that helps to reveal cell-type composition as well as cell-state heterogeneity for specific biological processes.Distinct sequencing platforms and processing pipelines may contribute to various results even for the same sequencing samples.Therefore,benchmarking sequencing platforms and processing pipelines was considered as a necessary step to interpret scRNA-seq data.However,recent comparing efforts were constrained in sequencing platforms or analyzing pipelines.There is still a lack of knowledge of analyzing pipelines matched with specific sequencing platforms in aspects of sensitivity,precision,and so on.Methods:We downloaded public scRNA-seq data that was generated by two distinct sequencers,NovaSeq 6000 and MGISEQ 2000.Then data was processed through the Drop-seq-tools,UMI-tools and Cell Ranger pipeline respectively.We calculated multiple measurements based on the expression profiles of the six platform-pipeline combinations.Results:We found that all three pipelines had comparable performance,the Cell Ranger pipeline achieved the best performance in precision while UMI-tools prevailed in terms of sensitivity and marker calling.Conclusions:Our work provided an insight into the selection of scRNA-seq data processing tools for two sequencing platforms as well as a framework to evaluate platform-pipeline combinations.展开更多
Current cell-type annotation tools for single-cell RNA sequencing(sc RNA-seq)data mainly utilize well-annotated source data to help identify cell types in target data.However,on account of privacy preservation,their r...Current cell-type annotation tools for single-cell RNA sequencing(sc RNA-seq)data mainly utilize well-annotated source data to help identify cell types in target data.However,on account of privacy preservation,their requirements for raw source data may not always be satisfied.In this case,achieving feature alignment between source and target data explicitly is impossible.Additionally,these methods are barely able to discover the presence of novel cell types.A subjective threshold is often selected by users to detect novel cells.We propose a universal annotation framework for sc RNA-seq data called sc EMAIL,which automatically detects novel cell types without accessing source data during adaptation.For new cell-type identification,a novel cell-type perception module is designed with three steps.First,an expert ensemble system measures uncertainty of each cell from three complementary aspects.Second,based on this measurement,bimodality tests are applied to detect the presence of new cell types.Third,once assured of their presence,an adaptive threshold via manifold mixup partitions target cells into‘‘known”and‘‘unknown”groups.Model adaptation is then conducted to alleviate the batch effect.We gather multi-order neighborhood messages globally and impose local affinity regularizations on‘‘known”cells.These constraints mitigate wrong classifications of the source model via reliable self-supervised information of neighbors.sc EMAIL is accurate and robust under various scenarios in both simulation and real data.It is also flexible to be applied to challenging single-cell ATAC-seq data without loss of superiority.The source code of sc EMAIL can be accessed at https://github.com/aster-ww/sc EMAIL and https://ngdc.cncb.ac.cn/biocode/tools/BT007335/releases/v1.0.展开更多
Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorde...Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.展开更多
Eucalyptus camaldulensis Dehnh. and E. globulus Labill. are economically important species for wood and pulpwood materials. Representative heights for assessing whole-tree values of cell-type proportions(vessels, fibe...Eucalyptus camaldulensis Dehnh. and E. globulus Labill. are economically important species for wood and pulpwood materials. Representative heights for assessing whole-tree values of cell-type proportions(vessels, fibers, ray and axial parenchyma percentages) using increment cores were examined by analysis of within-tree variations. Pattern differences were evaluated between trees and species in both radial and axial directions by statistical data analysis(Moses test). In E. camaldulensis,within-tree variation of vessel percentage was generally higher in the upper and outer regions of the trunk. In contrast, E. globulus within-tree variation was unclear. In both species, although no clear pattern of fiber percentages was observed, within-tree variations of ray and axial parenchyma levels were higher in the lower and inner regions.Significant differences in patterns were observed in the axial variation between species for vessel percentages and in the radial variation between trees of E. camaldulensis for ray parenchyma percentages. The representative heights for assessing whole-tree cell-type proportions were 0.8 mabove the ground for E. camaldulensis and 2.8 m for E.globulus, regardless of differences in tree height and pattern of within-tree variation of cell-type proportions.展开更多
An expression quantitative trait locus (eQTL) is a chromosomal region where genetic variants are associated with the expression levels of specific genes that can be both nearby or distant. The identifications of eQTLs...An expression quantitative trait locus (eQTL) is a chromosomal region where genetic variants are associated with the expression levels of specific genes that can be both nearby or distant. The identifications of eQTLs for different tissues, cell types, and contexts have led to a better understanding of the dynamic regulations of gene expressions and implications of functional genes and variants for complex traits and diseases. Although most eQTL studies have been performed on data collected from bulk tissues, recent studies have demonstrated the importance of cell-type-specific and context-dependent gene regulations in biological processes and disease mechanisms. In this review, we discuss statistical methods that have been developed to enable the detection of cell-type-specific and context-dependent eQTLs from bulk tissues, purified cell types, and single cells. We also discuss the limitations of the current methods and future research opportunities.展开更多
文摘Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an unquestioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed.
基金supported by IISER Tirupati and by an Early Career Research award from the Science and Engineering Research Board,Department of Science and Technology,Govt.of India(ECR/2016/001071)to E.R.K.K.D.acknowledges the CSIR-JRF fellowship and Bi-nationally supervised doctoral degree scholarship from DAAD(91730390)for her PhD.A.M.and A.P.G.acknowledge funding from IISER Tirupati for graduate studies.S.C.acknowledges funding from IISER Tirupati and the Ramalingaswami Re-entry Fellowship(BT/RLF/Re-entry/05/2018)Department of Biotechnology,Government of India.
文摘Rapid climate change has led to enhanced soil salinity,one of the major determinants of land degradation,resulting in low agricultural productivity.This has a strong negative impact on food security and environmental sustainability.Plants display various physiological,developmental,and cellular responses to deal with salt stress.Recent studies have highlighted the root cap as the primary stress sensor and revealed its crucial role in halotropism.The root cap covers the primary root meristem and is the first cell type to sense and respond to soil salinity,relaying the signal to neighboring cell types.However,it remains unclear how root-cap cells perceive salt stress and contribute to the salt-stress response.Here,we performed a root-cap cell-specific proteomics study to identify changes in the proteome caused by salt stress.The study revealed a very specific salt-stress response pattern in root-cap cells compared with non-rootcap cells and identified several novel proteins unique to the root cap.Root-cap-specific protein–protein interaction(PPI)networks derived by superimposing proteomics data onto known global PPI networks revealed that the endoplasmic reticulum(ER)stress pathway is specifically activated in root-cap cells upon salt stress.Importantly,we identified root-cap-specific jacalin-associated lectins(JALs)expressed in response to salt stress.A JAL10-GFP fusion protein was shown to be localized to the ER.Analysis of jal10 mutants indicated a role for JAL10 in regulating the ER stress pathway in response to salt.Taken together,our findings highlight the participation of specific root-cap proteins in salt-stress response pathways.Furthermore,root-cap-specific JAL proteins and their role in the salt-mediated ER stress pathway open a new avenue for exploring tolerance mechanisms and devising better strategies to increase plant salinity tolerance and enhance agricultural productivity.
基金Innovation Fund Denmark,No.4108-00008BThe Bagenkop NielsensØjen-Fond,No.115227+2 种基金Hørslev-Fonden,No.116967Beckett Fonden,No.116936Velux Foundation,No.1179261001/2.
文摘BACKGROUND Retinal organoids serve as excellent human-specific disease models for conditions affecting otherwise inaccessible retinal tissue from patients.They permit the isolation of key cell types affected in various eye diseases including retinal ganglion cells(RGCs)and Müller glia.AIM To refine human-induced pluripotent stem cells(hiPSCs)differentiated into threedimensional(3D)retinal organoids to generate sufficient numbers of RGCs and Müller glia progenitors for downstream analyses.METHODS In this study we described,evaluated,and refined methods with which to generate Müller glia and RGC progenitors,isolated them via magnetic-activated cell sorting,and assessed their lineage stability after prolonged 2D culture.Putative progenitor populations were characterized via quantitative PCR and immunocytochemistry,and the ultrastructural composition of retinal organoid cells was investigated.RESULTS Our study confirms the feasibility of generating marker-characterized Müller glia and RGC progenitors within retinal organoids.Such retinal organoids can be dissociated and the Müller glia and RGC progenitor-like cells isolated via magnetic-activated cell sorting and propagated as monolayers.CONCLUSION Enrichment of Müller glia and RGC progenitors from retinal organoids is a feasible method with which to study cell type-specific disease phenotypes and to potentially generate specific retinal populations for cell replacement therapies.
文摘During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, “the dirtiest place in the cell” in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.
基金supported by the National Natural Science Foundation of China(91632304 and 31500671)
文摘The autonomic nervous system controls various internal organs and executes crucial functions through sophisticated neural connectivity and circuits. Its dysfunction causes an imbalance of homeostasis and numerous human disorders. In the past decades, great efforts have been made to study the structure and functions of this system, but so far, our understanding of the classification of autonomic neuronal subpopulations remains limited and a precise map of their connectivity has not been achieved.One of the major challenges that hinder rapid progress in these areas is the complexity and heterogeneity of autonomic neurons. To facilitate the identification of neuronal subgroups in the autonomic nervous system, here we review the well-established and cutting-edge technologies that are frequently used in peripheral neuronal tracing and profiling, and discuss their operating mechanisms, advantages, and targeted applications.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.NRF-2021M2E8A1038938,No.NRF-2021R1F1A1048374,and No.NRF-2016R1A3B1908336)supported by a grant of the Korea Institute of Radiological and Medical Sciences(KIRAMS),funded by the Ministry of Science and ICT(MSIT),Republic of Korea(No.50051—2021,No.50623—2021)。
文摘The cell-type continuous electromagnetic radiation system is a demonstration device capable of generating high-power millimeter electromagnetic waves of a specific wavelength and observing their effects on living organisms.It irradiates a biological sample placed in a 30×30×50 cm^(3)cell with electromagnetic waves in the 3.15-mm-wavelength region(with an output of≥1 W)and analyzes the temperature change of the sample.A vacuum electronic device-based coupled-cavity backward-wave oscillator converts the electron energy of the electron beam into radiofrequency(RF)energy and radiates it to the target through an antenna,increasing the temperature through the absorption of RF energy in the skin.The system causes pain and ultimately reduces combat power.A cell-type continuous electromagnetic radiation system consisting of four parts—an electromagnetic-wave generator,a highvoltage power supply,a test cell,and a system controller—generates an RF signal of≥1 W in a continuous waveform at a 95-GHz center frequency,as well as a chemical solution with a dielectric constant similar to that of the skin of a living organism.An increase of 5°C lasting approximately 10 s was confirmed through an experiment.
基金This work was supported by Strategic Priority Research Program of Chinese Academy of Sciences(Nos.XDB38050200 and XDA26040304).
文摘Background:Single-cell RNA sequencing(scRNA-seq)technology is now becoming a widely applied method of transcriptome exploration that helps to reveal cell-type composition as well as cell-state heterogeneity for specific biological processes.Distinct sequencing platforms and processing pipelines may contribute to various results even for the same sequencing samples.Therefore,benchmarking sequencing platforms and processing pipelines was considered as a necessary step to interpret scRNA-seq data.However,recent comparing efforts were constrained in sequencing platforms or analyzing pipelines.There is still a lack of knowledge of analyzing pipelines matched with specific sequencing platforms in aspects of sensitivity,precision,and so on.Methods:We downloaded public scRNA-seq data that was generated by two distinct sequencers,NovaSeq 6000 and MGISEQ 2000.Then data was processed through the Drop-seq-tools,UMI-tools and Cell Ranger pipeline respectively.We calculated multiple measurements based on the expression profiles of the six platform-pipeline combinations.Results:We found that all three pipelines had comparable performance,the Cell Ranger pipeline achieved the best performance in precision while UMI-tools prevailed in terms of sensitivity and marker calling.Conclusions:Our work provided an insight into the selection of scRNA-seq data processing tools for two sequencing platforms as well as a framework to evaluate platform-pipeline combinations.
基金supported by the National Key R&D Program of China(Grant No.2021YFF1200902)the National Natural Science Foundation of China(Grant Nos.12126305 and 31871342)。
文摘Current cell-type annotation tools for single-cell RNA sequencing(sc RNA-seq)data mainly utilize well-annotated source data to help identify cell types in target data.However,on account of privacy preservation,their requirements for raw source data may not always be satisfied.In this case,achieving feature alignment between source and target data explicitly is impossible.Additionally,these methods are barely able to discover the presence of novel cell types.A subjective threshold is often selected by users to detect novel cells.We propose a universal annotation framework for sc RNA-seq data called sc EMAIL,which automatically detects novel cell types without accessing source data during adaptation.For new cell-type identification,a novel cell-type perception module is designed with three steps.First,an expert ensemble system measures uncertainty of each cell from three complementary aspects.Second,based on this measurement,bimodality tests are applied to detect the presence of new cell types.Third,once assured of their presence,an adaptive threshold via manifold mixup partitions target cells into‘‘known”and‘‘unknown”groups.Model adaptation is then conducted to alleviate the batch effect.We gather multi-order neighborhood messages globally and impose local affinity regularizations on‘‘known”cells.These constraints mitigate wrong classifications of the source model via reliable self-supervised information of neighbors.sc EMAIL is accurate and robust under various scenarios in both simulation and real data.It is also flexible to be applied to challenging single-cell ATAC-seq data without loss of superiority.The source code of sc EMAIL can be accessed at https://github.com/aster-ww/sc EMAIL and https://ngdc.cncb.ac.cn/biocode/tools/BT007335/releases/v1.0.
文摘Behavioral and molecular characterization of cell-type specific populations governing fear learning and behavior is a promising avenue for the rational identification of potential therapeutics for fear-related disorders.Identification of cell-type specific changes in neuronal translation following fear learning allows for targeted pharmacological intervention during fear extinction learning,mirroring possible treatment strategies in humans.Here we identify the central amygdala(Ce A)Drd2-expressing population as a fear-supporting population that is molecularly distinct from other,previously identified fear-supporting CeA populations.Sequencing of actively translating transcripts of Drd2 neurons identifies m RNAs that are differentially regulated following fear learning including Npy5r,Rxrg,Sst5r,Fgf3,Erb B4,Fkbp14,Dlk1,Ssh3 and Adora2a.Direct pharmacological manipulation of NPY5R,RXR,and ADORA2A confirms their importance in fear behavior and validates the present approach of identifying pharmacological targets for the modulation of emotional learning.
基金partly supported by the CREST program of JST(Japan Science and Technology)and the Oji Paper Company,Japan。
文摘Eucalyptus camaldulensis Dehnh. and E. globulus Labill. are economically important species for wood and pulpwood materials. Representative heights for assessing whole-tree values of cell-type proportions(vessels, fibers, ray and axial parenchyma percentages) using increment cores were examined by analysis of within-tree variations. Pattern differences were evaluated between trees and species in both radial and axial directions by statistical data analysis(Moses test). In E. camaldulensis,within-tree variation of vessel percentage was generally higher in the upper and outer regions of the trunk. In contrast, E. globulus within-tree variation was unclear. In both species, although no clear pattern of fiber percentages was observed, within-tree variations of ray and axial parenchyma levels were higher in the lower and inner regions.Significant differences in patterns were observed in the axial variation between species for vessel percentages and in the radial variation between trees of E. camaldulensis for ray parenchyma percentages. The representative heights for assessing whole-tree cell-type proportions were 0.8 mabove the ground for E. camaldulensis and 2.8 m for E.globulus, regardless of differences in tree height and pattern of within-tree variation of cell-type proportions.
文摘目的探讨自体骨髓干细胞(bone marrow stem cells,BMSCs)经胰背动脉移植治疗2型糖尿病(type 2 diabe-tes mellitus,T2DM)的有效性及安全性。方法回顾性分析2009年6月至2011年4月在我科住院符合纳入标准的6例2型糖尿病患者(3男3女),年龄(45.67±14.92)岁,实施自体骨髓干细胞移植。①动员骨髓;②采集骨髓;③分离骨髓干细胞;④将骨髓干细胞注入胰背动脉;⑤观察移植前后血糖、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、胰岛功能、C肽曲线下面积(area under curve for C-peptide,AUCC)及胰岛素用量等变化,记录治疗过程中及治疗后的不良反应;对干细胞移植的安全性及疗效进行评估。结果移植前后:①糖化血红蛋白由(10.33±2.78)%降至(7.05±0.90)%,有2例患者的糖化血红蛋白<7%;②空腹C肽(fasting C-peptide,FC-P)由(0.71±0.54)ng/ml升至(1.54±0.63)ng/ml(P<0.05),餐后2 h C肽(2 h postprandial C-peptide,2 h C-P)由(1.63±0.88)ng/ml升至(4.67±2.31)ng/ml(P<0.05),C肽曲线下面积由(2.29±1.31)ng/ml增至(6.05±2.94)ng/ml(P<0.05);③胰岛素用量由(27.17±13.08)U/d降到(18.63±7.04)U/d,其中2位患者停用皮下注射胰岛素改为口服药物降糖治疗;④自体骨髓干细胞移植过程中及术后随访均未观察到不良反应,移植前后肿瘤标志物及血淀粉酶均正常。结论自体骨髓来源干细胞移植可改善2型糖尿病患者的胰岛功能,减轻其对外源性降糖药物的依赖,且安全性可行。
文摘An expression quantitative trait locus (eQTL) is a chromosomal region where genetic variants are associated with the expression levels of specific genes that can be both nearby or distant. The identifications of eQTLs for different tissues, cell types, and contexts have led to a better understanding of the dynamic regulations of gene expressions and implications of functional genes and variants for complex traits and diseases. Although most eQTL studies have been performed on data collected from bulk tissues, recent studies have demonstrated the importance of cell-type-specific and context-dependent gene regulations in biological processes and disease mechanisms. In this review, we discuss statistical methods that have been developed to enable the detection of cell-type-specific and context-dependent eQTLs from bulk tissues, purified cell types, and single cells. We also discuss the limitations of the current methods and future research opportunities.
