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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

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Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK institute of developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

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 functions.In 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 formation.While the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still unclear.Astrocytes 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 brain.In the developing brain,astrocytes are primarily generated from radial glia after the neurogenic period.While 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

Rapid Unconscious Acquisition of Conditioned Fear with Low-Spatial-Frequency but Emotionally Neutral Stimuli

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Research 2024年第1期2023卷 753-762页

作者： Yujie Chen Si Chen Zhongju Sun Xilei Zhang Xiangyong Yuan Liang Wang Yi Jiang State Key Laboratory of Brain and Cognitive Sciences CAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of PsychologyChinese Academy of SciencesBeijing 100101China Department of psychology University of Chinese Academy of SciencesBeijing 100049China Chinese institute for Brain Research Beijing 102206China CAS Key Laboratory of Mental Health Institute of PsychologyChinese Academy of SciencesBeijing 100101China

It has long been proposed that emotionally“prepared”(i.e.,fear-related)stimuli are privileged in the unconscious acquisition of conditioned fear.However,as fear processing is suggested to highly depend on the coarse,low-spatial-frequency(LSF)components of the fear-related stimuli,it is plausible that LSF may play a unique role in the unconscious fear conditioning even with emotionally neutral stimuli.Here,we provided empirical evidence that,following classical fear conditioning,an invisible,emotionally neutral conditioned stimulus(CS+)with LSF,but not with high spatial frequency(HSF),can rapidly elicit stronger skin conductance responses(SCRs)and larger pupil diameters than its CS−counterpart.In comparison,consciously perceived emotionally neutral CS+with LSF and HSF elicited comparable SCRs.Taken together,these results support that the unconscious fear conditioning does not necessarily entail emotionally prepared stimuli but prioritizes LSF information processing and highlight the crucial distinctions between the unconscious and the conscious fear learning.These findings not only coincide with the postulation that a rapid,spatial-frequency-dependent subcortical route is engaged in unconscious fear processing but also suggest the existence of multiple routes for conscious fear processing.

关键词： neutral necessarily diameters

Non-B-form DNA is associated with centromere stability in newly-formed polyploid wheat

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Science China(Life Sciences) 2024年第7期67卷 1479-1488页

作者： Congyang Yi Qian Liu Yuhong Huang Chang Liu Xianrui Guo Chaolan Fan Kaibiao Zhang Yang Liu Fangpu Han institute of Genetics and developmental Biology Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Non-B-form DNA differs from the classic B-DNA double helix structure and plays a crucial regulatory role in replication and transcription.However,the role of non-B-form DNA in centromeres,especially in polyploid wheat,remains elusive.Here,we systematically analyzed seven non-B-form DNA motif profiles(A-phased DNA repeat,direct repeat,G-quadruplex,inverted repeat,mirror repeat,short tandem repeat,and Z-DNA)in hexaploid wheat.We found that three of these non-B-form DNA motifs were enriched at centromeric regions,especially at the CENH3-binding sites,suggesting that non-B-form DNA may create a favorable loading environment for the CENH3 nucleosome.To investigate the dynamics of centromeric non-B form DNA during the alloploidization process,we analyzed DNA secondary structure using CENH3 ChIP-seq data from newly formed allotetraploid wheat and its two diploid ancestors.We found that newly formed allotetraploid wheat formed more non-B-form DNA in centromeric regions compared with their parents,suggesting that non-B-form DNA is related to the localization of the centromeric regions in newly formed wheat.Furthermore,non-B-form DNA enriched in the centromeric regions was found to preferentially form on young LTR retrotransposons,explaining CENH3's tendency to bind to younger LTR.Collectively,our study describes the landscape of non-B-form DNA in the wheat genome,and sheds light on its potential role in the evolution of polyploid centromeres.

关键词： non-B-form DNA polyploid wheat centromere retrotransposon

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 diseases.Moreover,blood sphingolipids can also be used as biomarkers for disease diagnosis.This 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 chains.The possibility of using sphingolipids for disease prediction,diagnosis,and treatment is also discussed.Targeting 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

Pan Shuh:the founding figure of modern Chinese psychology

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Protein & Cell 2024年第4期15卷 235-238页

作者： Ligang Wang Tongqi Wei Liang Wang institute of psychology Chinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Mental Health Institute of PsychologyBeijing 100101China Department of psychology University of Chinese Academy of SciencesBeijing 101408China

Entering the lobby of the institute of psychology,Chinese Academy of Sciences,the first thing that catches the eye is the Pan Shuh Library.In the library,Pan Shuh’s six decades of life are displayed in the form of a life photo exhibition,representing 10 years of determination,10 years of wandering,10 years of exploration,10 years of following the path,10 years of self-improvement,and 10 years of propagation.These six decades not only reflect the life journey of Pan Shuh,the pioneer of Chinese psychology but also serve as a microcosm of the historical development of modern Chinese psychology(Qicheng Jing,Xiaolan Fu,2011).

关键词： founding representing Shu

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 plants.In-depth profiling of plant phosphoproteomes has been more technically challenging than that of animal phosphoproteomes.This 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 analysis.To 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)mode.The 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 cost-effectiveness.The 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 motifs.GreenPhos 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

A sphingolipid message promotes neuronal health across generations

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Neural Regeneration Research 2024年第11期19卷 2325-2326页

作者： Wenyue Wang Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Maternal nutrition can affect brain function of offspring in later life(Fitzgerald et al.,2020).Emerging studies have also shown that the maternal environment can modify susceptibility to neurodegenerative disease(Boots et al.,2023).Transmission of environmental information from mother to offspring depends on maternal nutrient provisioning.In the nematode Caenorhabditis elegans,maternal yolk,which is synthesized in the intestine and transferred to nourish oocytes and early embryos,can provide extranuclear inheritance factors to mediate phenotypic plasticity across generations.However,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

Functional divergences of natural variations of TaNAM-A1 in controlling leaf senescence during wheat grain filling

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Journal of Integrative Plant Biology 2024年第6期66卷 1242-1260页

作者： Longxi Zhou Guowei Chang Chuncai Shen Wan Teng Xue He Xueqiang Zhao Yanfu Jing Zhixiong Huang Yiping Tong Key Laboratory of Seed Innovation Institute of Genetics and Developmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences The Innovative Academy of Seed Design Chinese Academy of Sciences

Leaf senescence is an essential physiological process related to grain yield potential and nutritional quality. Green leaf duration(GLD) after anthesis directly reflects the leaf senescence process and exhibits large genotypic differences in common wheat; however, the underlying gene regulatory mechanism is still lacking. Here,we identified TaNAM-A1 as the causal gene of the major loci q GLD-6A for GLD during grain filling by map-based cloning. Transgenic assays and TILLING mutant analyses demonstrated that TaNAM-A1 played a critical role in regulating leaf senescence, and also affected spike length and grain size. Furthermore, the functional divergences among the three haplotypes of TaNAM-A1 were systematically evaluated. Wheat varieties with TaNAM-A1d(containing two mutations in the coding DNA sequence of TaNAM-A1) exhibited a longer GLD and superior yield-related traits compared to those with the wild type TaNAM-A1a. All three haplotypes were functional in activating the expression of genes involved in macromolecule degradation and mineral nutrient remobilization,with TaNAM-A1a showing the strongest activity and TaNAM-A1d the weakest. TaNAM-A1 also modulated the expression of the senescencerelated transcription factors TaNAC-S-7A and TaNAC016-3A. TaNAC016-3A enhanced the transcriptional activation ability of TaNAM-A1a by protein–protein interaction, thereby promoting the senescence process. Our study offers new insights into the fine-tuning of the leaf functional period and grain yield formation for wheat breeding under various geographical climatic conditions.

关键词： allelic variation leaf senescence map-based cloning TaNAM-A1 transcription factor Triticum aestivum