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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of developmental biology Department of Biology University of Patras Laboratory of cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

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Emerging roles and therapeutic potentials of sphingolipids in pathophysiology:emphasis on fatty acyl heterogeneity

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Journal of Genetics and Genomics 2024年第3期51卷 268-278页

作者： Jinming Mu Sin Man Lam Guanghou Shui State Key Laboratory of molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Lipidall Technologies Company Limited ChangzhouJiangsu 213000China

Sphingolipids not only exert structural roles in cellular membranes,but also act as signaling molecules in various physiological and pathological processes.A myriad of studies have shown that abnormal levels of sphingolipids and their metabolic enzymes are associated with a variety of human ***,blood sphingolipids can also be used as biomarkers for disease *** review summarizes the biosynthesis,metabolism,and pathological roles of sphingolipids,with emphasis on the biosynthesis of ceramide,the precursor for the biosynthesis of complex sphingolipids with different fatty acyl *** possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also *** endogenous ceramides and complex sphingolipids along with their specific fatty acyl chain to promote future drug development will also be discussed.

关键词： Sphingolipids Ceramide Therapeutic targets Microdomain Biomarker

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GreenPhos,a universal method for in-depth measurement of plant phosphoproteomes with high quantitative reproducibility

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molecular Plant 2024年第1期17卷 199-213页

作者： Xiaoxiao Duan Yuanya Zhang Xiahe Huang Xiao Ma Hui Gao Yan Wang Zhen Xiao Chengcheng Huang Zhongshu Wang Bolong Li Wenqiang Yang Yingchun Wang State Key Laboratory of molecular developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBejing 100101China University of Chinese Academy of Sciences Bejing 100049China Key Laboratory of Photobiology Instute of BotanyChinese Academy of SciencesBejing 100093China

Protein phosphorylation regulates a variety of important cellular and physiological processes in ***-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal *** is largely due to the need to improve protein extraction efficiency from plant cells,which have a dense cell wall,and to minimize sample loss resulting from the stringent sample clean-up steps required for the removal of a large amount of biomolecules interfering with phosphopeptide purification and mass spectrometry *** this end,we developed a method with a streamlined workflow for highly efficient purification of phosphopeptides from tissues of various green organisms including Arabidopsis,rice,tomato,and Chlamydomonas reinhardtii,enabling in-depth identification with high quantitative reproducibility of about 11000 phosphosites,the greatest depth achieved so far with single liquid chromatography-mass spectrometry(LC-MS)runs operated in a data-dependent acquisition(DDA)*** mainstay features of the method are the minimal sample loss achieved through elimination of sample clean-up before protease digestion and of desalting before phosphopeptide enrichment and hence the dramatic increases of time-and *** method,named GreenPhos,combined with single-shot LC-MS,enabled in-depth quantitative identification of Arabidopsis phosphoproteins,including differentially phosphorylated spliceosomal proteins,at multiple time points during salt stress and a number of kinase substrate *** is expected to serve as a universal method for purification of plant phosphopeptides,which,if samples are further fractionated and analyzed by multiple LC-MS runs,could enable measurement of plant phosphoproteomes with an unprecedented depth using a given mass spectrometry technology.

关键词： plant phosphoproteomics phosphopeptides LC–MS Arabidopsis salt stress

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Characterization of the infectivity of an Indonesian Zika virus strain in mammalian cell lines

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Asian Pacific Journal of Tropical Biomedicine 2024年第5期14卷 215-224页

作者： Justus Thomas Obiajulu Sievers Anom Bowolaksono R.Tedjo Sasmono Graduate School of biology Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia Eijkman Research Center for molecular biology National Research and Innovation AgencyCibinong 16911Indonesia cellular and molecular Mechanisms in Biological System Research Group Department of BiologyFaculty of Mathematics and Natural SciencesUniversitas IndonesiaDepok 16424Indonesia

Objective:To characterize the infection patterns and growth characteristics of the Zika virus(ZIKV)strain JMB-185 from Indonesia in various mammalian cell ***:ZIKV was grown in human(A549,HEK293,HepG2,Huh7,Jurkat,and THP-1)and non-human mammalian(RAW264.7,Vero,and Vero76)cell *** replication kinetics were measured using plaque assay,while intra-and extracellular viral RNA concentrations were assessed using *** cytometry was used to quantify the infected cells and cell viability was measured using an MTT *** ability of ZIKV to infect cell lines was visualized using a fluorescence immunostaining ***:This ZIKV strain preferentially infected the lung,kidney,and liver cell lines A549,HEK293,Huh7,Vero,and Vero76,but not the immune cells Jurkat,RAW264.7,and *** contrast,the ZIKV showed no sign of infection in HepG2 cells,while maintaining viral titer over 3 days post-infection,with no infection recorded in immunostaining,no increase in viral RNA,and no indication of cell ***:The Indonesian ZIKV strain has a similar infection profile as other strains,except for its poor infectivity on HepG2 *** on the growth characteristics of Indonesia ZIKV will help expand our understanding of the biology of ZIKV which will be useful for various applications including antiviral discovery.

关键词： Zika virus Infectivity Replication Cell lines In vitro

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Migratory mode transition of astrocyte progenitors in the cerebral cortex: an intrinsic or extrinsic cell process?

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Neural Regeneration Research 2024年第3期19卷 471-472页

作者： Michio Miyajima Hidenori Tabata Kazunori Nakajima department of Anatomy Keio University School of MedicineShinjuku-kuTokyoJapan department of molecular Neurobiology Institute for Developmental ResearchAichi Developmental Disability CenterKasugaiAichiJapan

The cerebral cortex is comprised of properly localized cell types that exert their specific *** the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Cossart and Garel,2022).For example,neocortical excitatory neurons are generated in the cerebral ventricular and subventricular zones,move to the developing cortical plate via radial migration,and reside in a radial array of six neuronal layers(Oishi and Nakajima,2018).On the other hand,cortical interneurons are mainly generated in ganglionic eminences,migrate tangentially across the cerebral cortex,and reach their final destinations in the cortex(Lim et al.,2018).The failure of neuronal migration leads to defects in cortical layer *** the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still *** are glial cells in the cerebral cortex with several functions,including metabolic support and synapse formation(Abbott et al.,2006;Bosworth and Allen,2017;Allen and Lyons,2018).For example,astrocytes establish synaptic connectivity in the developing brain while they contact numerous synapses and maintain optimal neuronal activity in the adult *** the developing brain,astrocytes are primarily generated from radial glia after the neurogenic *** a certain type of astrocyte called fibrous astrocytes populates the white matter,protoplasmic astrocytes migrate to the cortical plate during neural network formation.

关键词： cerebral migrate Abbott

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TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of developmental biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China department of Biochemistry and molecular biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

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OsPDR20 is an ABCG metal transporter regulating cadmium accumulation in rice

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Journal of Environmental Sciences 2024年第2期136卷 21-34页

作者： He Li Chao Li Di Sun Zhi Min Yang department of Biochemistry and molecular biology College of Life SciencesNanjing Agricultural UniversityNanjing 210095China

Cadmium(Cd)is a non-essential toxic heavy metal,seriously posing high environmental risks to human *** genetic resources relevant to functional genes is important for understanding the metal absorption and accumulation in crops and bioremediation of Cd-polluted *** study investigated a functionally uncharacterized ATP binding cassette transporter G family(ABCG)gene encoding a Pleiotropic Drug Resistance 20(PDR20)type metal transporter which is localized to the plasma membrane of ***20 was transcriptionally expressed in almost all tissues and organs in lifespan and was strongly induced in roots and shoots of young rice under Cd *** expression of OsPDR20 in a yeast mutant ycf1 sensitive to Cd conferred cellular tolerance with less Cd *** of OsPDR20 by RNA interference(RNAi)moderately attenuated root/shoot elongation and biomass,with reduced chlorophylls in rice grown under hydroponic medium with 2 and 10μmol/L Cd,but led to more Cd accumulation.A field trial of rice grown in a realistic Cd-contaminated soil(0.40 mg/kg)showed that RNAi plants growth and development were also compromised compared to wild-type(WT),with smaller panicles and lower spikelet fertility but little effect on yield of ***,OsPDR20 suppression resulted in unexpectedly higher levels of Cd accumulation in rice straw including lower leaves and culm and *** results suggest that OsPDR20 is actively involved in Cd accumulation and homeostasis in rice *** increased Cd accumulation in the RNAi plants has the potential application in phytoremediation of Cd-polluted wetland soils.

关键词： Rice ABCG transporter Cadmium accumulation Phytoremediation

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TabHLH27 orchestrates root growth and drought tolerance to enhance water use efficiency in wheat

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Journal of Integrative Plant biology 2024年第7期66卷 1295-1312页

作者： Dongzhi Wang Xiuxiu Zhang Yuan Cao Aamana Batool Yongxin Xu Yunzhou Qiao Yongpeng Li Hao Wang Xuelei Lin Xiaomin Bie Xiansheng Zhang Ruilian Jing Baodi Dong Yiping Tong Wan Teng Xigang Liu Jun Xiao Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050022China Key Laboratory of Crop biology College of Life SciencesShandong Agricultural UniversityTai'an 271018China State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China 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 Centre of Excellence for Plant and Microbial Science(CEPAMS) JIC‐CASBeijing 100101China

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid *** water scarcity,plants activate drought response signaling,yet the delicate balance between drought tolerance and development remains *** genome-wide association studies and transcriptome profiling,we identified a wheat atypical basic helix-loop-helix(b HLH)transcription factor(TF),Tab HLH27-A1,as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in *** HLH27-A1/B1/D1 knockout reduced wheat drought tolerance,yield,and water use efficiency(WUE).Tab HLH27-A1 exhibited rapid induction with polyethylene glycol(PEG)treatment,gradually declining over *** activated stress response genes such as Ta CBL8-B1 and Ta CPI2-A1 while inhibiting root growth genes like Ta SH15-B1 and Ta WRKY70-B1 under short-term PEG *** distinct transcriptional regulation of Tab HLH27-A1 involved diverse interacting factors such as Ta ABI3-D1 and Tab *** variations of Tab HLH27-A1influence its transcriptional responses to drought stress,with Tab HLH27-A1^(Hap-II)associated with stronger drought tolerance,larger root system,more spikelets,and higher WUE in ***,the excellent Tab HLH27-A1^(Hap-II)was selected during the breeding process in China,and introgression of Tab HLH27-A1^(Hap-II)allele improved drought tolerance and grain yield,especially under water-limited *** study highlights Tab HLH27-A1's role in balancing root growth and drought tolerance,providing a genetic manipulation locus for enhancing WUE in wheat.

关键词： drought tolerance GWAS root growth wheat WUE

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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

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Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children's Nutrition Research Center Department of Pediatrics Baylor College of Medicine department of molecular and cellular biology Section of Endocrinology Diabetes and Metabolism Department of Medicine Baylor College of Medicine Brain Glycemic and Metabolism Control department Pennington Biomedical Research Center Louisiana State University

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological ***,the body necessitates a stable supply of energy mainly provided by glucose for various bodily *** or low blood glucose levels would impair the physiological functions of various organs of the *** high blood glucose(i.e.,

关键词： HYPOGLYCEMIA

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