检索结果-南通市图书馆

Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing

Bone Research 2022年第3期10卷 469-481页

作者： Mubashir Ahmad Benjamin Thilo Krüger Torsten Kroll Sabine Vettorazzi Ann-Kristin Dorn Florian Mengele Sooyeon Lee Sayantan Nandi Dilay Yilmaz Miriam Stolz Naveen Kumar Tangudu David Carro Vázquez Johanna Pachmayr Ion Cristian Cirstea Maja Vujic Spasic Aspasia Ploubidou Anita Ignatius Jan Tuckermann Institute of Comparative Molecular Endocrinology(CME) Ulm UniversityHelmholtzstrasse 8/189081 UlmGermany Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany Leibniz Institute on Aging–Fritz Lipmann Institute(FLI) Beutenbergstrasse 11D-07745 JenaGermany Praxisklinik für Orthopädie Unfall-und Neurochirurgie Prof.Bischoff/Dr.Spies/Dr.Mengele89231 Neu-UlmGermany Paracelsus Medizinische Privatuniverstät Institute of PharmacyStrubergasse 215020 SalzburgAustria department of Endocrinology Ludwig Maximilians University MunichMunich 80336Germany present address:Institute of Orthopedic Research and Biomechanics Ulm UniversityHelmholtzstrasse 1489081 UlmGermany present address:UPMC Hillman Cancer Center Department of Pharmacology and Chemical BiologyUniversity of Pittsburgh5115 Center Avenue15232 PittsburghPAUSA present address:TAmiRNA GmbH Leberstrasse 201110 ViennaAustria

Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.

关键词： Cdk5 healing expression

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Tensile Strain Capacity Prediction of Engineered Cementitious Composites (ECC) Using Soft Computing Techniques

引用

Computer Modeling in Engineering & Sciences 2024年第3期138卷 2925-2954页

作者： Rabar H.Faraj Hemn Unis Ahmed Hardi Saadullah Fathullah Alan Saeed Abdulrahman Farid Abed Civil Engineering department University of HalabjaHalabjaIraq University of Sulaimani College of EngineeringCivil Engineering DepartmentSulaimaniIraq Civil Engineering department Komar University of Science and TechnologySulaimaniIraq department of Engineering Kurdistan Institution for Strategic Studies and Scientific ResearchesSulaimaniIraq department of Civil Engineering American University of SharjahSharjah26666UAE

Plain concrete is strong in compression but brittle in tension,having a low tensile strain capacity that can significantly degrade the long-term performance of concrete structures,even when steel reinforcing is present.In order to address these challenges,short polymer fibers are randomly dispersed in a cement-based matrix to forma highly ductile engineered cementitious composite(ECC).Thismaterial exhibits high ductility under tensile forces,with its tensile strain being several hundred times greater than conventional concrete.Since concrete is inherently weak in tension,the tensile strain capacity(TSC)has become one of the most extensively researched properties.As a result,developing a model to predict the TSC of the ECC and to optimize the mixture proportions becomes challenging.Meanwhile,the effort required for laboratory trial batches to determine the TSC is reduced.To achieve the research objectives,five distinct models,artificial neural network(ANN),nonlinear model(NLR),linear relationship model(LR),multi-logistic model(MLR),and M5P-tree model(M5P),are investigated and employed to predict the TSCof ECCmixtures containing fly ash.Data from115 mixtures are gathered and analyzed to develop a new model.The input variables include mixture proportions,fiber length and diameter,and the time required for curing the various mixtures.The model’s effectiveness is evaluated and verified based on statistical parameters such as R2,mean absolute error(MAE),scatter index(SI),root mean squared error(RMSE),and objective function(OBJ)value.Consequently,the ANN model outperforms the others in predicting the TSC of the ECC,with RMSE,MAE,OBJ,SI,and R2 values of 0.42%,0.3%,0.33%,0.135%,and 0.98,respectively.

关键词： Engineered cementitious composites fly ash curing time tensile strain capacity modeling

来源：

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

Signal pathways and precision therapy of small-cell lung cancer

引用

Signal Transduction and Targeted Therapy 2022年第7期7卷 2293-2310页

作者： Min Yuan Yu Zhao Hendrik-Tobias Arkenau Tongnei Lao Li Chu Qing Xu department of Oncology Shanghai Tenth People’s HospitalTongji University200072 ShanghaiChina Drug Development Unit Sarah Cannon Research InstituteLondonUK department of Oncology Centro Medico BO CHIMacaoSARChina department of Radiation Oncology Fudan University Shanghai Cancer Center200032 ShanghaiChina present address:department of Oncology Shanghai Medical CollegeFudan University200032 ShanghaiChina

Small-cell lung cancer(SCLC)encounters up 15%of all lung cancers,and is characterized by a high rate of proliferation,a tendency for early metastasis and generally poor prognosis.Most of the patients present with distant metastatic disease at the time of clinical diagnosis,and only one-third are eligible for potentially curative treatment.Recently,investigations into the genomic make-up of SCLC show extensive chromosomal rearrangements,high mutational burden and loss-of-function mutations of several tumor suppressor genes.Although the clinical development of new treatments for SCLC has been limited in recent years,a better understanding of oncogenic driver alterations has found potential novel targets that might be suitable for therapeutic approaches.Currently,there are six types of potential treatable signaling pathways in SCLC,including signaling pathways targeting the cell cycle and DNA repair,tumor development,cell metabolism,epigenetic regulation,tumor immunity and angiogenesis.At this point,however,there is still a lack of understanding of their role in SCLC tumor biology and the promotion of cancer growth.Importantly optimizing drug targets,improving drug pharmacology,and identifying potential biomarkers are the main focus and further efforts are required to recognize patients who benefit most from novel therapies in development.This review will focus on the current learning on the signaling pathways,the status of immunotherapy,and targeted therapy in SCLC.

关键词： metabolism immunity alterations

来源：

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

Functional Analysis of Semi-conserved Transit Peptide Motifs and Mechanistic Implications in Precursor Targeting and Recognition

引用

Molecular Plant 2016年第9期9卷 1286-1301页

作者： Kristen Holbrook Chitra Subramanian Prakitchai Chotewutmontri L. Evan Reddick Sarah Wright Huixia Zhang Lily Moncrief Barry D. Bruce department of Biochemistry Cellular and Molecular Biology Graduate Program in Plant Physiology and Genetics Graduate School of Genome Science and Technology department of Botany department of BotanyUniversity of Tennessee Knoxville TN 37996 USA present address: department of Infectious Disease St. Jude Children's Research Hospital Memphis TN 38105 USA present address: Institute of Molecular Biology University of Oregon Eugene OR 97403 USA present address: department of Microbiology University of Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas TX 75390 USA present address: Albert R. Mann Library Cornell University Ithaca NY 14850 USA present address: U.S. Food and Drug Administration 10903 New Hampshire Avenue Silver Spring MD 20993 USA

Over 95% of plastid proteins are nuclear-encoded as their precursors containing an N-terminal extension known as the transit peptide （TP）. Although highly variable, TPs direct the precursors through a conserved, posttranslational mechanism involving translocons in the outer （TOC） and inner envelope （TOC）. The organelle import specificity is mediated by one or more components of the Toc complex. However, the high TP diversity creates a paradox on how the sequences can be specifically recognized. An emerging model of TP design is that they contain multiple loosely conserved motifs that are recognized at different steps in the targeting and transport process. Bioinformatics has demonstrated that many TPs contain semiconserved physicochemical motifs, termed FGLK. In order to characterize FGLK motifs in TP recognition and import, we have analyzed two well-studied TPs from the precursor of RuBisCO small subunit （SStp） and ferredoxin （Fdtp）. Both SStp and Fdtp contain two FGLK motifs. Analysis of large set mutations （-85） in these two motifs using in vitro, in organello, and in vivo approaches support a model in which the FGLK domains mediate interaction with TOC34 and possibly other TOC components. In vivo import analysis suggests that multiple FGLK motifs are functionally redundant. Furthermore, we discuss how FGLK motifs are required for efficient precursor protein import and how these elements may permit a convergent function of this highly variable class of targeting sequences.

关键词： chloroplast biology protein translocation Toc34 transit peptide cell biology

来源：

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

Exclusion and Co-expression of Aversive Olfactory Long-Term Memories in Drosophila

引用

Neuroscience Bulletin 2022年第6期38卷 657-660页

作者： Bohan Zhao Xuchen Zhang Janjan Zhao Qian Li School of Life Sciences IDG/MeGovern Institute for Brain ResearchTsinghua UniversityBeijing 100084China Tsinghua-Peking Center for Life Sciences Bejing 100084China present address:Centre for Neural Circuits and Behaviour University of OxfordOxford OX13SRUK present Addrss:department of Molecular and Cellular Physiology and Howard Hughes Medical InstituteStanford University School of MedicineStanfordCA 94305USA

Long-term memory(LTM)allows animals to use remote past experiences to guide current and future decisions.One of the widely-used animal models for LTM research is the fruit-fly Drosophila melanogaster,which can form different types of LTM after different learning paradigms[1-6].Spaced training-induced LTM(spLTM),perhaps the most studied Drosophila LTM,requires multiple repeated learning trials with a 15-min resting interval between each trial.For decades,spLTM has been considered the only aversive olfactory LTM that can last for>7 days[1].Recently,two other types of LTM,context-dependent LTM(cLTM)[5]and merged LTM(mLTM)[6],have been discovered with the same long duration as spLTM,and can be formed with only one aversive learning trial.

关键词： Drosophila Olfactory melanogaster

来源：

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

Cellular and Molecular Requirements for Polar PIN Targeting and Transcytosis in Plants

引用

Molecular Plant 2008年第6期1卷 1056-1066页

作者： Jurgen Kleine-Vehn tukasz tangowski Justyna Wisniewska Pankaj Dhonukshe Philip B Brewer Jiri Friml department of Plant Systems Biology VIB and Department of Molecular Genetics Ghent University 9052 Gent Belgium Zentrum fur Molekularbiologie der Pflanzen (ZMBP) Universitat Tubingen 72076 Tubingen Germany present address: Institute of General and Molecular Biology Nicolas Copernicus University 87-100 Torun Poland present address: department of Biology Utrecht University 3508 TB Utrecht The Netherlands present address: Centre for Integrative Legume Research University of Queensland Brisbane Australia

The polar, sub-cellular localization of PIN auxin efflux carriers determines the direction of intercellular auxin flow, thus defining the spatial aspect of auxin signalling. Dynamic, transcytosis-like relocalizations of PIN proteins occur in response to external and internal signals, integrating these signals into changes in auxin distribution. Here, we examine the cellular and molecular mechanisms of polar PIN delivery and transcytosis. The mechanisms of the ARF-GEF-dependent polar targeting and transcytosis are well conserved and show little variations among diverse Arabidopsis ecotypes consistent with their fundamental importance in regulating plant development. At the cellular level, we refine previous findings on the role of the actin cytoskeleton in apical and basal PIN targeting, and identify a previously unknown role for microtubules, specifically in basal targeting. PIN protein delivery to different sides of the cell is mediated by ARFdependent trafficking with a previously unknown complex level of distinct ARF-GEF vesicle trafficking regulators. Our data suggest that alternative recruitment of PIN proteins by these distinct pathways can account for cell type- and cargo-specific aspects of polar targeting, as well as for polarity changes in response to different signals. The resulting dynamic PIN positioning to different sides of cells defines a three-dimensional pattern of auxin fluxes within plant tissues.

关键词： cytoskeleton polarity protein targeting.

来源：

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

Measuring nanoparticles in liquid with attogram resolution using a microfabricated glass suspended microchannel resonator

引用

Microsystems & Nanoengineering 2022年第4期8卷 261-270页

作者： Mehdi Mollaie Daryani Tomás Manzaneque Jia Wei Murali Krishna Ghatkesar department of Precision and Microsystems Engineering Delft University of TechnologyDelftThe Netherlands department of Microelectronics Delft University of TechnologyDelftThe Netherlands present address:department of Microelectronics Delft University of TechnologyDelftThe Netherlands

The use of nanoparticles has been growing in various industrial fields,and concerns about their effects on health and the environment have been increasing.Hence,characterization techniques for nanoparticles are essential.Here,we present a silicon dioxide microfabricated suspended microchannel resonator(SMR)to measure the mass and concentration of nanoparticles in a liquid as they flow.We measured the mass detection limits of the device using laser Doppler vibrometry.This limit reached a minimum of 377 ag that correspond to a 34 nm diameter gold nanoparticle or a 243 nm diameter polystyrene particle,when sampled every 30 ms.We compared the fundamental limits of the measured data with an ideal noiseless measurement of the SMR.Finally,we measured the buoyant mass of gold nanoparticles in real-time as they flowed through the SMR.

关键词： resonator suspended nanoparticles

来源：

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

An Epigenetic Role for Disrupted Paternal Gene Expression in Postzygotic Seed Abortion in Arabidopsis Interspecific Hybrids

引用

Molecular Plant 2015年第12期8卷 1766-1775页

作者： Ryan C. Kirkbride Helen Hong Yu Gyoungju Nah Changqing Zhang Xiaoli Shi Z. Jeffrey Chen department of Molecular biosciences Center for Computational Biology and Bioinformatics and Institute for Cellular and Molecular Biology The University of Texas at Austin Austin TX 78712 USA These authors contributed equally to this article. present address: department of Plant Science Research Institute of Agriculture and Life Sciences Seoul National University Seou1151-921 South Korea present address: Plants for Human Health Institute North Carolina State University 600 Laureate Way Kannapolis NC 28081 USA present address: Institute of Theoretical Physics Chinese Academy of Sciences PO Box 2735 Beijing 100080 China

Interspecific hybrids often increase the levels of heterozygosity and hybrid vigor, but some interspecific hybrid seeds are aborted shortly after fertilization. The mechanism behind this postzygotic seed abortion is poorly understood. Here, we report genome-wide analysis of allelic expression changes in developing siliques and seeds in three F1 interspecific crosses between Arabidopsis thaliana （Col, Ler, or C24） and Arabidopsis arenosa. The majority of maternally expressed genes （MEGs） were shared among all three F1 interspecific crosses, whereas ~90% of 272 paternally expressed genes （PEGs） were found only in one or two F1 crosses, suggesting a role for disrupted paternal gene expression in seed abortion that varies in different crosses. Consistent with this notion, 12 PEGs in the infertile interspecific hybrids matched MEGs in fertile intraspecific hybrids. This disruption of PEGs in the interspecific hybrids was consistent with the upregulation of the genes in the paternal-excess interploidy cross （2X6） between a diploid mother and a hexaploid father, leading to the seed abortion. Moreover, a subset of PEGs in the interspecific crosses were also upregulated in the intraspecific hybrid metlXWT or meaXWT, in which the mutant of MET1 （DNA METHYL TRANSFERASE1） or MEDEA, a Polycomb Repressive Complex2 gene, was used as the maternal parent. These data suggest that maternal epigenetic factors and paternal gene expression play important roles in the postzygotic seed abortion in interspecific hybrids or neo-allopolyploids.

关键词： epigenetics imprinting paternal gene expression polyploidy hybrid incompatibility seeddevelopment

来源：

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

Reciprocal inhibition of expression between RAV1 and BES1 modulates plant growth and development in Arabidopsis

引用

Journal of Integrative Plant Biology 2023年第5期65卷 1226-1240页

作者： Dami Yang Hyun-young Shin Hyun Kyung Kang Yun Shang So Young Park Dong-Hoon Jeong Kyoung Hee Nam department of Biological Sciences Sookmyung Women's UniversitySeoul 04310Republic of Korea Research Institute for Women's HealthSookmyung Women's UniversitySeoul 04310Republic of Korea department of Life Science and Multidisciplinary Genome Institute Hallym UniversityChuncheon 24252Republic of Korea Present Address:Peking University Institute of Advanced Agricultural ScienceWeifang 261325China

RAV1(Related to ABI3/VP1)is a plant-specific B3 and AP2 domain-containing transcription factor that acts as a negative regulator of growth in many plant species.The expression of RAV1 is downregulated by brassinosteroids(BRs);large-scale transcriptome analyses have shown that the expression of RAV1 was previously targeted by BRI1-EMS-SUPPRESOR1(BES1)and BRASSINAZOLE-RESISTANT1(BZR1),which are critical transcription factors for the BR-signaling process.Using RAV1-overexpressing transgenic plants,we showed that RAV1 overexpression reduced the BR signaling capacity,resulting in the downregulation of BR biosynthetic genes and BES1 expression.Furthermore,we demonstrated that BES1,not BZR1,is directly bound to the RAV1 promoter and repressed RAV1 expression,and vice versa;RAV1 is also bound to the BES1 promoter and repressed BES1 expression.This mutual inhibition was specific to RAV1 and BES1 because RAV1 exhibited binding activity to the BZR1 promoter but did not repress BZR1 expression.We observed that constitutively activated BR signaling phenotypes in bes1-D were attenuated by the repression of endogenous BES1 expression in transgenic bes1-D plants overexpressing RAV1.RNA-sequencing analysis of RAV1-overexpressing transgenic plants and bes1-D mutant plants revealed differentially expressed genes by RAV1 and BES1 and genes that were oppositely co-regulated by RAV1 and BES1.RAV1 and BES1 regulated different transcriptomes but co-regulated a specific set of genes responsible for the balance between growth and defense.These results suggested that the mutual inhibitory transcriptional activities of RAV1 and BES1 provide fine regulatory mechanisms for plant growth and development.

关键词： BES1 growth modulation RAV1 transcriptional regulation

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

RIP1 （ROP Interactive Partner 1）/ICR1 Marks Pollen Germination Sites and May Act in the ROP1 Pathway in the Control of Polarized Pollen Growth

引用

Molecular Plant 2008年第6期1卷 1021-1035页

作者： Shundai Li Ying Gu An Yan Elizabeth Lord Zhen-Biao Yang Center for Plant Cell Biology Institute of Integrative Genome Biology and Department of Botany and Plant Sciences University of California Riverside CA92521 USA present address: Energy biosciences Institute University of California Berkeley Berkeley CA 94720 USA

Rho family small GTPases are universal signaling switches in the control of cell polarity in eukaryotic cells. Their polar distribution to the cell cortex is critical for the execution of their functions, yet the mechanism for this distribution is poorly understood. Using a yeast two-hybrid method, we identified RIP1 （ROP interactive partner 1）, which belongs to a family of five members of novel proteins that share a C-terminal region that interacts with ROP. When expressed in Arabidopsis pollen, green fluorescence protein GFP-tagged RIP1 was localized to the nucleus of mature pollen. When pollen grains were hydrated in germination medium, GFP-RIP1 switched from the nucleus to the cell cortex at the future pollen germination site and was maintained in the apical cortex of germinating pollen and growing pollen tubes. RIP1 was found to interact with ROP1 in pollen tubes, and the cortical RIP1 localization was influenced by the activity of ROP1. Overexpression of RIP1 induced growth depolarization in pollen tubes, a phenotype similar to that induced by ROP1 overexpression. Interestingly, RIP1 overexpression enhanced GFP-ROP1 recruitment to the plasma membrane （PM） of pollen tubes. Based on these observations, we hypothesize that RIP1 is involved in the positive feedback regulation of ROP1 localization to the PM, leading to the establishment of a polar site for pollen germination and pollen tube growth.

关键词： RIP1 Pollen Germination Polarized Pollen Growth Control

来源：

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

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：