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

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

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.lee Ryota l.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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Estimation of j—R Curves for Small-Sized COEC Specimens and Its Application Considering Crack-Tip Cons tr aints

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Acta Mechanica Solida Sinica 2019年第3期32卷 261-276页

作者： G.W.He C.Bao l.X.Cai y.j.Wu Applied Mechanics and Structure Safety Key laboratory of Sichuan Province School of Mechanics and Engineering Southwest Jiaotong University Chengdu 610031 China

The normalization method has been employed to estimate the j-resistance (j—R) curves for C-shaped outside edge-notched compression (COEC) specimens of SA-508 steel. The COEC specimens present the lowest j—R curves in comparison with other three types of specimens. Based on the j—Q—M met hod, the constraint parame ter Q determined at the mid-plane in the through-thickness direction of the specimen is used to approximately quantify the threedimensional crack-tip constraint for COEC specimens. Combining with the previous experiments on j—R curves, the constraint-coirected j—R curves for SA-508 steel specimens are given, which may be used to predict the fracture toughness of actual cracked components in structural integrity assessment.

关键词： Ductile fracture toughness COEC specimen Dimensionless load separation principle Normalization method Crack-tip constraint j-Q-M method

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William j.Flerlage Mark l.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services University of the Health Sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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Spin-correlation function of the fully frustrated Ising model and ±j Ising spin glass on a square lattice

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Chinese Physics B 2013年第6期22卷 549-552页

作者： M y Ali j Poulter Department of Mathematics Faculty of ScienceMahidol University

In this work we study the correlation function of the ground state of a two-dimensional fully frustrated Ising model as well as spin glass. The Pfaffian method is used to calculate free energy and entropy as well as the correlation function. We estimate the exponent of spin correlation function for the fully frustrated model and spin glass. In this paper an overview of the latest results on the spin correlation function is presented.

关键词： spin glass correlation function exponent square lattice

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Mathematical modelling of axonal microtubule bundles under dynamic torsion

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Applied Mathematics and Mechanics(English Edition) 2018年第6期39卷 829-844页

作者： j.y.WU Hong yUAN l.y.lI MOE Key laboratory of Disaster Forecast and Control in Engineering Institute of Applied MechanicsJinan University School of Engineering University of Plymouth

Owing to its viscoelastic nature, axon exhibits a stress rate-dependent me- chanical behavior. An extended tension-shear chain model with Kelvin-Voigt viscoelas- ticity is developed to illustrate the micromechanical behavior of the axon under dynamic torsional conditions. Theoretical closed-form expressions are derived to predict the de- formation, stress transfer, and failure mechanism between microtubule （MT） and tau protein while the axon is sheared dynamically. The results obtained from the present an- alytical solutions demonstrate how the MT-tau interface length, spacing between the tau proteins, and loading rate affect the mechanical properties of axon. Moreover, it is found that the MTs are more prone to rupture due to the contributions from the viscoelastic effects. Under the torsional force, the MTs are so long that the stress concentrates at the loaded end where axonal MTs will break. This MT-tau protein dynamics model can help to understand the underlying pathology and molecular mechanisms of axonal injury. Additionally, the emphasis of this paper is on the micromechanical behavior of axon, whereas this theoretical model can be equally applicable to other soft or hard tissues, owning the similar fibrous structure.

关键词： torsion biocomposite diffuse axonal injury (DAI) Kelvin-Voigt viscoelas-tic model dynamic response tension-shear chain model

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Numerical study of the circular opening effect on mechanical behaviour of rock under confinement

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journal of Rock Mechanics and Geotechnical Engineering 2019年第6期11卷 1201-1210页

作者： y.l.Gui j.l.Shang j.j.Ma Z.y.Zhao school of engineering newcastle universitynewcastle upon tynene17ruunited kingdom school of civil and environmental engineering nanyang technological university639798singapore school of civil engineering sun yat-sen universityguangzhou510275china

Opening holes in rock including their size and distribution can affect the performance of rock-related structures.A good understanding on this will contribute to,for example,rock cavern design,and construction,tunnelling,and mining *** improve the understanding,a comprehensive investigation of the opening hole effect on the rock mechanical behaviour under biaxial loading condition is carried out by virtue of a hybrid continuum-discrete element *** specimens with both single hole and multi-hole of various radii are investigated and compared with the cases subjected to uniaxial *** is demonstrated that the confining pressure can increase both the stiffness and strength due to delaying the crack initiation and *** increase due to the confining pressure is more evident for the compressive *** single hole specimens with 0.75 mm radius hole,the increase ratio of the compressive strength is a linear increasing function with width and the increase ratio ranges from 2.15 for the specimen with 3.5 mm width to 2.45 for 10 mm *** the single hole specimen with 10 mm width,the increase ratio starts at 2.13 for the specimen with 0.75 mm radius hole,ascending to the peak of 2.37 for the specimen with 1 mm radius hole,followed by a decline to 2.2 for the specimen with 1.25 mm radius ***,for the multi-hole specimens,the increase ratio varies from 1.66 to *** addition,to verify the influence of confining pressure magnitude on the performance of the rock specimens,totalling 10 confining pressure levels are applied and *** simulation results show that even though there are opening holes in the specimens,the simulated compressive strength generally follows the generalised Hoek-Brown model.

关键词： Rock with opening Simulation Biaxial loading Strength Stiffness

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Floor dust erosion during early stages of coal dust explosion development

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International journal of Mining Science and Technology 2019年第6期29卷 825-830页

作者： Marcia l.Harris michael.j.Sapko Center for Disease Control and Prevention (CDC) National Institute for Occupational Safety and Health (NIOSH) Pittsburgh Mining Research Division (PMRD)

An ignition of methane and air can generate enough air flow to raise mixtures of combustible coal and rock *** expanding high temperature combustion products ignite the suspended dust mixture and will continue to propagate following the available combustible fuel *** the concentration of the dispersed rock dust is sufficient,the flame will stop ***-scale explosion tests were conducted within the National Institute for Occupational Safety and Health(NIOSH)lake lynn Experimental Mine(llEM)to measure the dynamic pressure history and the post-explosion dust scour *** aim of this effort is to provide quantitative data on depth of dust removal during the early stages of explosion development and its relationship to the depth of floor dust collected for assessing the incombustible content most likely to participate in the combustion *** experimental work on dust removal on is not only important for coal mine safety but also for industrial dust explosions.

关键词： Underground Coal dust Explosion Dust sampling

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Advances in additively manufactured titanium alloys by powder bed fusion and directed energy deposition:Microstructure,defects,and mechanical behavior

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journal of Materials Science & Technology 2024年第16期183卷 32-62页

作者： H.y.Ma j.C.Wang P.Qin y.j.liu l.y.Chen l.Q.Wang l.C.Zhang Centre for Advanced Materials and Manufacturing School of EngineeringEdith Cowan University270 Joondalup DriveJoondalupPerthWA 6027SA School of Engineering M050The University of Western Australia35 Stirling HighwayCrawleyPerthWA 6009SA Institute of Metals College of Material Science and EngineeringChangsha University of Science&TechnologyChangsha 410004China School of Material Science and Engineering Jiangsu University of Science and TechnologyZhenjiang 212100China State Key laboratory of Metal Matrix Composites School of Material Science and EngineeringShanghai Jiao Tong UniversityShanghai 200240China

Ti and its alloys have been broadly adopted across various industries owing to their outstanding proper-ties,such as high strength-to-weight ratio,excellent fatigue performance,exceptional corrosion resistance and so *** manufacturing(AM)is a complement to,rather than a replacement for,traditional manufacturing *** enhances flexibility in fabricating complex components and resolves machin-ing challenges,resulting in reduced lead times for custom ***,owing to distinctions among various AM technologies,Ti alloys fabricated by different AM methods usually present differences in mi-crostructure and defects,which can significantly influence the mechanical performance of built ***,having an in-depth knowledge of the scientific aspects of fabrication and material properties is crucial to achieving high-performance Ti alloys through different AM *** article reviews the mechanical properties of Ti alloys fabricated by two mainstream powder-type AM techniques:powder bed fusion(PBF)and directed energy deposition(DED).The review examines several key aspects,en-compassing phase formation,grain size and morphology,and defects,and provides an in-depth analysis of their influence on the mechanical behaviors of Ti *** review can aid researchers and engi-neers in selecting appropriate PBF or DED methods and optimizing their process parameters to fabricate high-performance Ti alloys for a wide range of industrial applications.

关键词： Powder bed fusion Directed energy deposition Titanium alloys Phase transformation Defects Mechanical property

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