检索结果-南通市图书馆

Bridging the gap:axonal fusion drives rapid functional recovery of the nervous system

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2018年第4期13卷 591-594页

作者： Jean-Sébastien Teoh Michelle Yu-Ying Wong Tarika Vijayaraghavan Brent Neumann Neuroscience program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash University

Injuries to the central or peripheral nervous system frequently cause long-term disabilities because damaged neurons are unable to efficiently *** inherent deficiency necessitates the need for new treatment options aimed at restoring lost function to *** to humans,a number of species possess far greater regenerative capabilities,and can therefore provide important insights into how our own nervous systems can be *** particular,several invertebrate species have been shown to rapidly initiate regeneration post-injury,allowing separated axon segments to *** process,known as axonal fusion,represents a highly efficient repair mechanism as a regrowing axon needs to only bridge the site of damage and fuse with its separated counterpart in order to re-establish its original *** recent findings in the nematode Caenorhabditis elegans have expanded the promise of axonal fusion by demonstrating that it can restore complete function to damaged ***,we revealed the importance of injury-induced changes in the composition of the axonal membrane for mediating axonal fusion,and discovered that the level of axonal fusion can be enhanced by promoting a neuron＇s intrinsic growth potential.A complete understanding of the molecular mechanisms controlling axonal fusion may permit similar approaches to be applied in a clinical setting.

关键词： axonal fusion axon regeneration nervous system repair nerve injury phosphatidylserine functional repair axonal transport Caenorhabditis elegans

The structure of Rap1 in complex with RIAM reveals specificity determinants and recruitment mechanism

在线全文

学校读者我要写书评

暂无评论

Journal of Molecular Cell Biology 2014年第2期8卷 128-139页

作者： Hao Zhang Yu-Chung Chang Mark L. Brennan Jinhua Wu developmental Therapeutics program Fox Chase Cancer Center 333 Cottman Avenue Philadelphia PA 19111 USA

The small GTPase Rap1 induces integrin activation via an inside-out signaling pathway mediated by the Rapl-interacting adaptor mol- ecule （RIAM）. Blocking this pathway may suppress tumor metastasis and other diseases that are related to hyperactive integrins. However, the molecular basis for the specific recognition of RIAM by Rap1 remains largely unknown. Herein we present the crystal structure of an active, GTP-bound GTPase domain of Rap1 in complex with the Ras association （RA）-pleckstrin homology （PH） structural module of RIAM at 1.65 A. The structure reveals that the recognition of RIAM by Rap1 is governed by side-chain interactions. Several side chains are critical in determining specificity of this recognition, particularly the Lys31 residue in Rap1 that is oppositely charged compared with the Glu31/Asp31 residue in other Ras GTPases. Lys31 forms a salt bridge with RIAM residue Glu212, making it the key specificity determinant of the interaction. We also show that disruption of these interactions results in reduction of Rapl：RIAM association, leadingto a loss of co-clustering and cell adhesion. Our findings elucidate the molecular mechanism by which RIAM med- iates Rapl-induced integrin activation. The crystal structure also offers new insight into the structural basis for the specific recruitment of RA-PH module-containing effector proteins by their smaU GTPase partners.

关键词： RIAM Rap1 integrin signaling inside-out signaling crystal structure RA-PH

Ex vivo expansion of hematopoietic stem cells

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2015年第9期58卷 839-853页

作者： XIE JingJing ZHANG ChengCheng Taishan Scholar Immunology program Binzhou Medical University Departments of Physiology and developmental Biology University of Texas Southwestern Medical Center

Ex vivo expansion of hematopoietic stem cells(HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing.

关键词： ex vivo expansion hematopoietic stem cells niche signal transduction cord blood transplantation SCID-repopulating cell genome ed

A sphingolipid message promotes neuronal health across generations

在线全文

学校读者我要写书评

暂无评论

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 *** 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 ***,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

Molecular therapeutics in pancreas cancer

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastrointestinal Oncology 2016年第4期8卷 366-379页

作者： Vignesh Narayanan Colin D Weekes Division of Medical Oncology Department of Medicine Developmental Therapeutics Program University of Colorado Cancer Center University of Colorado School of Medicine

The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma(PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease.

关键词： Pancreas neoplasm Vaccines Targeted therapy Immunotherapy Kirsten rat sarcoma oncogene

Genome-wide Analysis of Kelch Repeatcontaining F-box Family

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Journal of Integrative Plant Biology 2007年第6期49卷 940-952页

作者： Yujin Sun Xiaofan Zhou Hong Ma Department of Biology and the Huck Institutes of Life Sciences Intercollege Graduate program in Cell and developmental Biology The Pennsylvania State University University Park PA 16802 USA

The ubiquitin-dependent protein degradation pathway plays diverse roles in eukaryotes. Previous studies indicate that both F-box and Kelch motifs are common in a variety of organisms. F-box proteins are subunits of E3 ubiquitin ligase complexes called SCFs （SKP1, Cullinl, F-box protein, and Rbxl）; they have an N-terminal F-box motif that binds to SKP1 （S-phase kinase associated protein）, and often have C-terminal protein-protein interaction domains, which specify the protein substrates for degradation via the ubiquitin pathway. One of the most frequently found protein interaction domains in F-box proteins is the Kelch repeat domain. Although both the F-box and Kelch repeats are ancient motifs, Kelch repeats-containing F-box proteins （KFB） have only been reported for human and Arabidopsis previously. The recent sequencing of the rice genome and other plant genomes provides an opportunity to examine the possible evolution history of KFB. We carried out extensive BLAST searches to identify putative KFBs in selected organisms, and analyzed their relationships phylogenetically. We also carried out the analysis of both gene duplication and gene expression of the KFBs in rice and Arabidopsis. Our study indicates that the origin of KFBs occurs before the divergence of animals and plants, and plant KFBs underwent rapid gene duplications.

关键词： Arabidopsis thaliana F-box motif Kelch repeats Kelch repeats-containing F-box proteins SCF SKP1 like.

Complete canine spinal cord transection model: a large animal model for the translational research of spinal cord regeneration

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2018年第1期61卷 115-117页

作者： Sufang Han Xing Li Zhifeng Xiao Jianwu Dai State Key Laboratory of Molecular developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences

Traumatic spinal cord injury (SCI) usually results in devastating neurologic deficits and disability. In the United States,approximately 12,500 new cases are reported each year, while an estimated 100,000–140,000 new cases occur every year in China (National Spinal Cord Injury Statistical Center, 2016).Spinal cord injuries are highly disabling and primarily affect young adults, and therefore create great psychological and financial burden on the affected individuals and their families.

关键词： In Complete canine spinal cord transection model SCI

Regulation of the protein stability of POSH and MLK family

在线全文

学校读者我要写书评

暂无评论

Protein & Cell 2010年第9期1卷 871-878页

作者： Chunyan Wang Yang Tao Yaqing Wang Zhiheng Xu Key Laboratory of Molecular and developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Sequential activation of the JNK pathway components,including Rac1/Cdc42,MLKs(mixed-lineage kinases),MKK4/7 and JNKs,plays a required role in many cell death *** components are organized by a scaffold protein,POSH(Plenty of SH3’s),to ensure the effective activation of the JNK pathway and cell death upon apoptotic *** have shown recently that the expression of POSH and MLK family proteins are regulated through protein *** generating a variety of mutants,we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell *** addition,POSH’s ability to induce apoptosis is correlated with its stability as well as its MLK binding *** family’s stability,like that of POSH,requires activation of ***,we were surprised to find out that the widely used dominant negative(d/n)form of c-Jun could down-regulate MLK’s stability,indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.

关键词： the JNK pathway protein stability POSH MLK family and poptosis

Adverse effects of metal exposure on chemotaxis towards water-soluble attractants regulated mainly by ASE sensory neuron in nematode Caenorhabditis elegans

在线全文

学校读者我要写书评

暂无评论

Journal of Environmental Sciences 2009年第12期21卷 1684-1694页

作者： XING Xiaojuan, DU Min, ZHANG Yanfen, WANG Dayong Key Laboratory of developmental Genes and Human Disease in Ministry of Education, Department of Genetics and developmental Biology, Southeast University Medical School, Nanjing 210009, China. Key Laboratory of developmental Genes and Human Disease in Ministry of Education Department of Genetics and Developmental Biology Southeast University Medical School Nanjing 210009 China

Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans. Our data suggested that exposure to high concentrations of metals, such as Pb, Cu, Ag, and Cr, would result in severe defects of chemotaxis to water-soluble attractants of NaCl, cAMP, and biotin. Moreover, the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies, relative lengths of sensory endings in ASE neurons, and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants. In addition, the dendrite morphology could be noticeably changed in animals exposed to 150 μmol/L of Pb, Cu, and Ag. Furthermore, we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5 μmol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 μmol/L. Therefore, impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.

关键词： chemotaxis water-soluble attractant ASE neuron che-1 Caenorhabditis elegans