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Genes & Diseases 2016年第2期3卷 153-158页

作者： Avudaiappan Maran Kristen L.Shogren michael j.yaszemski Department of Orthopedics Mayo ClinicRochesterMN 55905USA

Osteosarcoma is a primary bone tumor that affects children and young *** estrogen metabolite 2-methoxyestradiol(2-ME)induces cell death in osteosarcoma *** determine whether 2-ME actions involve the control of protein synthesis,we studied the effect of 2-ME on eukaryotic initiation factor 4E(eIF4E)and eIF4E-binding protein 1(4E-BP1)in MG63 osteosarcoma *** results show that 2-ME treatment increases the association of eIF4E with 4E-BP1 in osteosarcoma ***,2-ME decreases the binding of eIF4E protein to 7-methyl-guanosine cap structure,indicating that 2-ME treatment results in the inhibition of translational *** findings are further supported by the inhibition of protein synthesis in 2-ME-treated osteosarcoma *** together,our studies show that 2-ME-mediated antitumor effects in osteosarcoma cells involve the regulation of protein synthesis,and translational machinery could serve as a target in the treatment of osteosarcoma.

关键词： 2-Methoxyestradiol 4E-BP Estrogen metabolite eIF4E Osteosarcoma

A novel triple immunoenzyme staining enables simultaneous identification of all muscle fiber types on a single skeletal muscle cryosection from normal, denervated or reinnervated rats

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Neural Regeneration Research 2017年第8期12卷 1357-1364页

作者： Peng Wu Shuya Zhang Robert j.Spinner michael Torres Lizardi Yudong Gu Cong Yu michael j.yaszemski Anthony j.Windebank Huan Wang Department of Neurological Surgery Mayo Clinic Rochester MN USA Department of Hand Surgery Huashan Hospital Fudan University Shanghai China Shanghai Tenth People's Hospital Tongji University Shanghai China Department of Neurology Mayo Clinic Rochesterl MN USA Department of Medicine New York Presbyterian Weill Cornell Medical Center New York NY USA Shanghai Key Laboratory of Peripheral Nerve and Microsurgery Shanghai China Departments of Orthopedic Surgery and Biomedical Engineering Mayo Clinic Rochester MN USA

Triple immunofluorescence staining has recently been developed to simultaneously identify all muscle fibers on a single cryosection which is helpful for clinical and basic research, but it has disadvantages such as fast photobleaching and unclear outlines of muscle fibers. Triple immunoenzyme staining（TIE） is likely to avoid these disadvantages. In this study, we aimed to establish a sensitive and specific TIE technique to identify fiber types in normal, denervated, and reinnervated rat muscles, and to develop a systematic sampling method for muscle fiber quantification. Tibialis anterior and soleus from normal, denervated, and reinnervated Lewis rat hind limbs were used. Five consecutive cryosections were cut from each muscle, including one for TIE and four for single immunoenzyme staining（SIE）. The TIE was performed using the polymerized reporter enzyme staining system for the first two antigens（A4.74 for My HC-IIA, BA-F8 for My HC-I） and alkaline phosphatase staining system for the third antigen（BF-F3 for My HC-IIB）, followed by corresponding detective systems and respective chromogens. The type of muscle fibers was quantified by systematic sampling at 12.5%, 25%, 33% and 50% of all muscle fibers, and was compared with that acquired from counting all the fibers（100%）. All muscle fiber phenotypes, including pure and hybrid, could be simultaneously identified on a single TIE cryosection with clear outlines. The fiber types on TIE slides matched well with their respective counterpart on the consecutive SIE slides with a 95% match rate. Systematic sampling of 12.5% fibers could represent the true fiber type distribution of the entire muscle section. Our results suggest that novel TIE can effectively visualize fiber types in normal, denervated or reinnervated rat muscles.

关键词： nerve regeneration muscle fiber phenotyping immunohistochemistry triple immunoenzymestaining myosin heavy chain rats neural regeneration

STIM1 expression is associated with osteosarcoma cell survival

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Chinese journal of Cancer Research 2019年第1期31卷 203-211页

作者： jie Zang Dongqing Zuo Kristen L.Shogren Carl T.Gustafson Zifei Zhou michael A Thompson Ruiwei Guo Y.S.Prakash Lichun Lu Wei Guo Avudaiappan Maran michael j.yaszemski Department of Orthopedic Surgery Mayo ClinicRochesterMN 55905USA Musculoskeletal Tumor Center Peking University People's HospitalBeijing 100044China Department of Orthopaedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Department of Anesthesiology Mayo ClinicRochesterMN 55905USA Department of Cardiology Kunming General Hospital of Chengdu Military Command of PLA Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN 55905USA

Objective: To examine the role of store-operated calcium entry(SOCE) and stromal interaction molecule 1(STIM1) in survival and migration of osteosarcoma cells and investigate what blockade of store-operated Ca^(2+)contributes to the regulation of osteosarcoma ***: First, we examined the expression levels of STIM1 in osteosarcoma cell lines by Western analysis and in tissue specimens by immunohistochemistry. Second, we investigated the effect of SOCE and STIM1 on osteosarcoma cell viability using MTS assays and on cell proliferation using colony formation. Third, we investigated the role of SOCE and STIM1 in cell migration using wound healing assays and Boyden chamber assays. Finally, we studied the effect of SOCE on the nuclear factor of activated T-cells cytoplasmic 1(NFATc1)activity by luciferase ***: STIM1 was overexpressed in osteosarcoma cell lines and tissue specimens and was associated with poor survival of osteosarcoma patients. Also, inhibition of SOCE and STIM1 decreased the cell viability and migration of osteosarcoma cells. Furthermore, our results showed that blockade of store-operated Ca^(2+) channels involved down-regulation of NFATc1 in osteosarcoma ***: STIM1 is essential for osteosarcoma cell functions, and STIM1 and Ca^(2+) entry pathway could be further explored as molecular targets in the treatment of osteosarcoma.

关键词： Calcium NFATc1 osteosarcoma SOCE STIM1

Key changes in denervated muscles and their impact on regeneration and reinnervation

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Neural Regeneration Research 2014年第20期9卷 1796-1809页

作者： Peng Wu Aditya Chawla Robert j.Spinner Cong Yu michael j.yaszemski Anthony j.Windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Department of Hand Surgery Huashan HospitalFudan University Department of Orthopedic Surgery the Second Affiliated HospitalZhejiang University School of Medicine Department of Orthopedic Surgery Wake Forest School of MedicineWinston-SalemNCUSA Departments of Orthopedic Surgery and Biomedical Engineering Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA Shanghai Key Laboratory of Peripheral Nerve and Microsurgery

The neuromuscular junction becomes progressively less receptive to regenerating axons if nerve repair is delayed for a long period of time. It is difficult to ascertain the denervated muscle＇s residual receptivity by time alone. Other sensitive markers that closely correlate with the extent of denervation should be found. After a denervated muscle develops a fibrillation potential, muscle fiber conduction velocity, muscle fiber diameter, muscle wet weight, and maximal isometric force all decrease; remodeling increases neuromuscular junction fragmentation and plantar area, and expression of myogenesis-related genes is initially up-regulated and then down-regulated. All these changes correlate with both the time course and degree of denervation. The nature and time course of these denervation changes in muscle are reviewed from the literature to explore their roles in assessing both the degree of detrimental changes and the potential success of a nerve repair. Fibrillation potential amplitude, muscle fiber conduction velocity, muscle fiber diameter, mRNA expression levels of myogenic regulatory factors and nicotinic acetylcholine receptor could all reflect the severity and length of denervation and the receptiveness of denervated muscle to regenerating axons, which could possibly offer an important clue for surgical choices and predict the outcomes of delayed nerve repair.

关键词： nerve regeneration denervation reinnervation fibrillation potential muscle fiberconduction velocity muscle fiber diameter maximal isometric force neuromuscular junction geneexpression neural regeneration

NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno michael K.E.Schafer Sudena Wang michael j.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

Identifying suitable areas for plenter forest management

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FOREST ECOSYSTEMS 2025年第1期12卷 83-92页

作者： Leiter, Mathias Pucher, Christoph Kessler, michael Hoeuronigsberger, Ferdinand Lexer, Manfred j. Vacik, Harald Hasenauer, Hubert Univ Nat Resources & Life Sci BOKU Inst Silviculture Peter Jordan Str 82 A-1190 Vienna Austria Univ Nat Resources & Life Sci BOKU Inst Forest Engn Peter Jordan Str 82 A-1190 Vienna Austria

Plenter forests, also known as uneven-aged or continuous cover forests enhance forest resilience and resistance against disturbances compared to even-aged forests. They are considered as an adaptation option to mitigate climate change effects. In this study, we present a conceptual approach to determine the potentially suitable area for plenter forest management within central European mixed species forests and apply our approach to the case study area in Styria, the south-eastern Province of Austria. The concept is based on ecological and technical-economic constraints and considers expected future climate conditions and its impact on plenter forest management. For each 1 ha forest pixel, we assess the ecological conditions for plenter forest management according to the autecological growth conditions of silver fir, and at least one additional shade tolerant tree species. The technical-economic constraints are defined by slope (<= 30%) and distance to the next forest road (<= 100 m) to ensure cost-efficient harvesting. The results show that under current climate conditions 28.1% or 305,349 ha of the forests in Styria are potentially suitable for plenter forest management. For the years 2071-2100 and under the climate change scenario RCP 4.5, the potential area decreases to 286,098 ha (26.3% of the total forest area) and for the scenario RCP 8.5 to 208,421 ha (19.1% of the total forest area). The main reason for these changes is the unfavourable growing conditions for silver fir in the lowlands, while in the higher elevations silver fir is likely to expand. Our results may serve forest managers to identify areas suitable for plenter forests and assist in the transformation of even-aged pure forests to uneven-aged forests to increase resistance, resilience, and biodiversity under climate change.

关键词： Plenter forest Uneven-aged forest management Tree species suitability Tree harvesting Transformation

The hydrodynamic RAM effect:Review of historic experiments,model developments and simulation

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Defence Technology(防务技术) 2025年第2期44卷 150-178页

作者： Georg A.Heilig michael May Fraunhofer Institute for High-Speed Dynamics Ernst-Mach-Institute(EMI)Ernst-Zermelo-Strasse 4Freiburg 79104Germany

The Hydrodynamic Ram(HRAM)effect occurs when a high kinetic energy projectile penetrates a fluid filled area,e.g.,a liquid filled *** projectile transfers its momentum and kinetic energy to the fluid,what causes a sudden,local pressure rise,further expanding as primary shock wave in the fluid and developing a *** is possible that the entire tank ruptures due to the loads transferred through the fluid to its surrounding *** the past decades,additionally to experimental investigations,HRAM has been studied using various computational approaches particularly focusing on the description of the Fluid-Structure Interaction(FSI).This article reviews the published experimental,analytical and numerical results and delivers a chronological overview since the end of World War ***,HRAM mitigation measures are highlighted,which have been developed with the experimental,analytical and numerical toolboxes matured over the past 80 years.

关键词： Fluid-structure-interaction(FSI) Euler-Lagrange-Coupling Hydrodynamic RAM effect HRAM

Identifying suitable areas for plenter forest management

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Forest Ecosystems 2025年第01期 83-92页

作者： Mathias Leiter Christoph Pucher michael Kessler Ferdinand H?nigsberger Manfred j.Lexer Harald Vacik Hubert Hasenauer Institute of Silviculture University of Natural Resources and Life Sciences (BOKU) Institute of Forest Engineering University of Natural Resources and Life Sciences (BOKU)

Plenter forests, also known as uneven-aged or continuous cover forests enhance forest resilience and resistance against disturbances compared to even-aged forests. They are considered as an adaptation option to mitigate climate change effects. In this study, we present a conceptual approach to determine the potentially suitable area for plenter forest management within central European mixed species forests and apply our approach to the case study area in Styria, the south-eastern Province of Austria. The concept is based on ecological and technicaleconomic constraints and considers expected future climate conditions and its impact on plenter forest management. For each 1 ha forest pixel, we assess the ecological conditions for plenter forest management according to the autecological growth conditions of silver fir, and at least one additional shade tolerant tree species. The technical-economic constraints are defined by slope(≤30%) and distance to the next forest road(≤100 m) to ensure cost-efficient harvesting. The results show that under current climate conditions 28.1% or 305,349 ha of the forests in Styria are potentially suitable for plenter forest management. For the years 2071–2100 and under the climate change scenario RCP 4.5, the potential area decreases to 286,098 ha(26.3% of the total forest area)and for the scenario RCP 8.5 to 208,421 ha(19.1% of the total forest area). The main reason for these changes is the unfavourable growing conditions for silver fir in the lowlands, while in the higher elevations silver fir is likely to expand. Our results may serve forest managers to identify areas suitable for plenter forests and assist in the transformation of even-aged pure forests to uneven-aged forests to increase resistance, resilience, and biodiversity under climate change.

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Seismites of the Late Triassic Lockatong Formation,Pennsylvania,USA:implications for Newark Basin border fault movement

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journal of Palaeogeography 2025年第1期14卷 1-14页

作者： Edward L.Simpson michael C.Wizevich David L.Fillmore Department of Physical Sciences Kutztown University of Pennsylvania Department of Earth and Space Sciences Central Connecticut State University

Numerous soft-sediment deformation structures(SSDS) within thin-bedded, heterolithic lacustrine shoreline deposits of the Upper Triassic Tumble Falls Member, Lockatong Formation of eastern Pennsylvania, demonstrate liquefaction, fluidization and shearing features processes affecting sediment. This study employs thin-section analysis of SSDS to interpret them as probable seismites from the Triassic-jurassic Newark Basin. Sedimentary structures include right-lateral offset of desiccation cracks and ichnofossils, thrust,reverse, and normal faults with mm-scale offsets, horsts and grabens, lateral spreads, and single and complex multiple networks of dikes and sills and associated sedimentary volcanoes, thin mudflows on a paleosurface linked to sediment dikes, load and flame structures, ball and pillow structures, recumbent folds, and incipient breccias. Dike fill consists of mudstone, angular sedimentary clasts, sandstone margins with mudstone cores,and plastically deformed sediment fill. The SSDS indicate that Late Triassic lacustrine shoreline sediments were subjected to forces, probably compressive with a minimal shear component reflected in the offset of the dikes and ichnofossils, that induced liquefaction followed by fluidization and vertical movement of *** forces that altered sediment vertical stability, leading to deformation of the sediment included gravitationally unstable density gradients, vertical shear stress, and gravitational body forces. SSDS can be induced by seismic and aseismic processes. However, this unique combination of forces and resulting sedimentary structures indicate an origin by earthquake activity, likely produced by the nearby, active Newark Basin border fault system. The Lockatong Formation SSDS seismites improve our understanding via thin section analysis of the rheology and preservation potential of SSDS in lacustrine shoreline deposits, critical for the geologic history of Newark Basin, as well as the refinement for paleos

关键词： Seismites Triassic Lockatong Formation Lacustrine Soft-sediment deformation structures

Modeling compositional heterogeneity resolves deep phylogeny of flowering plants

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Plant Diversity 2025年第1期47卷 13-20页

作者： Yongli Wang Yan-Da Li Shuo Wang Erik Tihelka michael S.Engel Chenyang Cai Biofuels Institute School of Environmental and Safety EngineeringJiangsu UniversityZhenjiang 212013China Key Laboratory of Palaeobiology and Petroleum Stratigraphy Nanjing Institute of Geology and PalaeontologyChinese Academy of SciencesNanjing 210008China School of Earth Sciences University of BristolLife Sciences BuildingTyndall AvenueBristol BS81TQUnited Kingdom College of Marine Science and Biological Engineering Qingdao University of Science and TechnologyQingdao 266042China Division of Invertebrate Zoology American Museum of Natural HistoryNew YorkNY 10024-5192USA Facultad de Ciencias Biologicas Universidad Nacional Mayor de San MarcosLima 15081Peru Departamento de Entomología Museo de Historia NaturalUniversidad Nacional Mayor de San MarcosLima 15072Peru

Angiosperms experienced one of the most remarkable radiations of land plants and are now the dominant autotrophs in terrestrial *** phylogenomic studies based on large-scale data from plastid,mitochondrial,or nuclear transcriptomes/genomes and increased taxon sampling have provided unprecedent resolution into the phylogeny of flowering ***,owing to ancient rapid radiations,the interrelationships among the five lineages of Mesangiospermae,the vast majority of angiosperms,remain *** we show that,although plastid and mitochondrial genomes lack sufficient phylogenetic signal for resolving deeper phylogeny,the relationships among five mesangiosperm lineages can be confidently resolved under better-fitting models using genome-scale *** to our Bayesian cross-validation and model test in a maximum likelihood framework,siteheterogeneous models(e.g.,CAT-GTR+G4,LG+C20+F+G)outperform site-homogeneous or partition models often used in previous *** site-heterogeneous models,the approximately unbiased test favored our preferred tree recovered from various datasets:Ceratophyllales(coontails)are robustly recovered as sister to monocots,and they together are sister to the clade comprising magnoliids,Chloranthales,and *** phylogenomic analyses resolve the last enigma of the deeper phylogeny of angiosperms and emphasize the efficacy of modeling compositional heterogeneity in resolving rapid radiations of plants.

关键词： Angiosperms Ceratophyllales Phylogenomics Radiation Methodological factors CAT model