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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： Benjamin r.Helmold Angela Ahrens Zachary Fitzgerald p.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SpAST spastin

Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural regeneration research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.r.Groh Moein Yaqubi Qiao-Ling Cui Jo Anne Stratton G.r.Wayne Moore Jack p.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by robertson and río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus rNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

Microstructural Features of Spray-Deposited Immiscible Bearing Alloys Al-43Sn and Al-7Sn-1.3Cu-1.3Ni

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Journal of Materials Science & Technology 2003年第5期19卷 437-443页

作者： O.p.pandey Thapar Institute of Engineering & Technology Deemed University Patiala-147004 India

Two commercial grade aluminum based immiscible bearing alloys were spray-deposited using convergent-divergent type of nozzle. The processing parameters for spray-deposition were adjusted in such a way that most of the droplets arrived on the deposition substrate in either liquid or semi-liquid state. The microstructural features of spray-formed and as-cast alloys are compared. In spray-formed alloys equiaxed grains were observed. The cell boundaries and intercellular regions were observed to be decorated with sub-micron sized particles whereas in normal casting the second phase was observed to be segregated along grain boundaries. The morphology and distribution of second phase were observed to have similarity with those in over-spread and atomized powders produced under similar processing conditions. The microstructural features observed with variation in spray conditions are discussed in detail.

关键词： Spray deposition Immiscible bearing alloys Microstructure Atomization

Landslide Susceptibility Mapping Using rBFN-Based Ensemble Machine Learning Models

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 467-500页

作者： Landslide Susceptibility Mapping Using rBFN-Based Ensemble Machine Learning Models Duc-Dam Nguyen Nguyen Viet Tiep Quynh-Anh Thi Bui Hiep Van Le Indra prakash romulus Costache Manish pandey Binh Thai pham Faculty of Civil Engineering University of Transport TechnologyThanh XuanHa Noi100000Vietnam Faculty of Hydraulic Engineering Hanoi University of Civil EngineeringHa Noi100000Vietnam DDG(r)Geological Survey of India Gandhinagar382010India research Institute of the University of Bucharest Bucharest050663Romania National Institute of Hydrology and Water Management Bucharest013686Romania Department of Civil Engineering Transilvania University of BrasovBrasov500152Romania Danube Delta National Institute for research and Development Tulcea820112Romania Marwadi University research Center(MUrC) Marwadi UniversityRajkotGujaratBharat360003India Department of Civil Engineering Faculty of Engineering&TechnologyMarwadi UniversityRajkotGujaratBharat360003India

This study was aimed to prepare landslide susceptibility maps for the pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined radial Basis Function Networks(rBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-rBFN,MB-rBFN,and ***,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer perceptron Neural Network(MLp),were employed for comparison and *** models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to *** factors were instrumental in predicting the output variable,which was the probability of landslide *** analysis of the models’performance indicated that the DG-rBFN model,with an Area Under rOC Curve(AUC)of 0.931,outperformed the other *** AB-rBFN model achieved an AUC of 0.929,the MB-rBFN model had an AUC of 0.913,and the MLp model recorded an AUC of *** results suggest that the advanced ensemble ML model DG-rBFN was more accurate than traditional statistical model,single MLp model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.

关键词： Landslide susceptibility map spatial analysis ensemble modelling information values(IV)

Coarse to Fine: The role of Severe plastic Deformation in Advancing Titanium-Based Medical Implants - A Comprehensive review

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Journal of Wuhan University of Technology(Materials Science) 2025年第1期40卷 295-306页

作者： Dragana r Mihajlović Bojan I Međo Ivana Lj Cvijović-Alagić Veljko r Djokić Faculty of Technology and Metallurgy University of BelgradeKarnegijeva 411120 BelgradeSerbia Vinča Institute of Nuclear Sci-ences-National Institute of the republic of Serbia University of Belgrade11001BeogradSerbia Innovation Centre of the Faculty of Technology and Metallurgy Karnegijeva 411120 BelgradeSerbia

This paper describes severe plastic deformation(SpD)procedures,which are utilized to form an ultrafine-grained structure in metallic *** the SpD process,a solid material sample is subjected to very high loads without a significant change in sample *** the present work,the high-pressure torsion(HpT)process,as one of the SpD techniques,which achieves a high degree of deformation and ensures refinement of the microstructure,will be discussed in more *** that grain size control is accepted as a method to obtain materials with desired characteristics,an overview of the properties of ultrafine-grained titanium-based biomaterials to be used in medicine is ***,particular attention is dedicated to the influences of HpT process parameters,primarily hydrostatic pressure,and number of revolutions during torsion,on the grain size and physical and mechanical characteristics(modulus of elasticity,microhardness,and tensile properties),corrosion resistance,and biocompatibility of the titanium-based biomaterials.A review of the literature indicates that titanium-based materials obtained by the SpD process show improved mechanical and physical properties without losing biocompatibility and corrosion resistance,which suggests that these methods of obtaining implants are something that should be further developed in the future.

关键词： high-pressure torsion process ultrafine-grained titanium-based materials electrochemical anodization physical properties mechanical properties

Graph Convolutional Network Based Fault Detection and Identification for Low-voltage DC Microgrid

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Journal of Modern power Systems and Clean Energy 2023年第3期11卷 917-926页

作者： Ambuj pandey Soumya r.Mohanty Department of Electrical Engineering Indian Institute of Technology(BHU)VaranasiUttar PradeshIndia IEEE

This paper presents a novel fault detection and identification method for low-voltage direct current(DC)microgrid with meshed *** proposed method is based on graph convolutional network(GCN),which utilizes the explicit spatial information and measurement data of the network topology to identify a *** has a more substantial feature extraction ability even in the presence of noise and bad *** adjacency matrix for GCN is developed by considering the network topology as an inherent *** bus voltage and line current samples after faults are regarded as the node ***,the DC microgrid model is developed using pSCAD/EMTDC simulation,and fault simulation is carried out by considering different possible events that include environmental and physical *** performance of the proposed method under different conditions is compared with those of different machine learning techniques such as convolutional neural network(CNN),support vector machine(SVM),and fully connected network(FCN).The results reveal that the proposed method is more effective than others at detecting and classifying *** method also possesses better robustness under the presence of noise and bad data.

关键词： DC microgrid graph convolution network fault detection topological information

Deep scientific drilling results from Koyna and Killari earthquake regions reveal why Indian shield lithosphere is unusual, thin and warm

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Geoscience Frontiers 2016年第5期7卷 851-858页

作者： O.p.pandey CSIr-National Geophysical research Institute Uppal Road Hyderabad 500007 India

The nature of crustal and lithospheric mantle evolution of the Archean shields as well as their subsequent deformation due to recent plate motions and sustained intraplate geodynamic activity, has been a subject of considerable interest. In view of this, about three decades ago, a new idea was put forward suggesting that out of all shield terrains, the Indian shield has an extremely thin lithosphere（w100 km,compared to 250e350 km, elsewhere）, apart from being warm, non-rigid, sheared and deformed. As expected, it met with scepticism by heat flow and the emerging seismic tomographic study groups, who on the contrary suggested that the Indian shield has a cool crust, besides a coherent and thick lithosphere（as much as 300e400 km） like any other shield. However, recently obtained integrated geological and geophysical findings from deep scientific drillings in 1993 Killari（M w： 6.3） and 1967 Koyna（M w： 6.3）earthquake zones, as well as newly acquired geophysical data over other parts of Indian shield terrain,have provided a totally new insight to this debate. Beneath Killari, the basement was found consisting of high density, high velocity mid crustal amphibolite to granulite facies rocks due to exhumation of the deeper crustal layers and sustained granitic upper crustal erosion. Similar type of basement appears to be present in Koyna region too, which is characterized by considerably high upper crustal ***, such type of crust is depleted in radiogenic elements, it resulted into lowering of heat flow at the surface, increase in heat flow contribution from the mantle, and upwarping of the lithosphereasthenosphere boundary. Consequently, the Indian shield lithosphere has become unusually thin and warm. This study highlights the need of an integrated geological, geochemical and geophysical approach in order to accurately determine deep crust-mantle thermal regime in continental areas.

关键词： Indian lithosphere Killari seismic zone Deep drilling results Mafic crust Geodynamics Heat flow

Emerging potential of progranulin-dependent SorCS2 signaling in healthy and diseased nervous systems

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Neural regeneration research 2025年第9期20卷 2591-2593页

作者： Alena Salasova Anders Nykjær Danish research Institute of Translational Neuroscience DANDrITE-Nordic EMBL partnership for Molecular Medicine and Centre of Excellence PROMEMODepartment of BiomedicineAarhus UniversityAarhusDenmark

The formation of the mammalian nervous system and its maturation into sensory,motor,cognitive,and behavioral circuits is a complex process that begins during early embryogenesis and lasts until young *** neurodevelopm... 详细信息

关键词： progr jointly CS2

Effect of electroslag remelting and homogenization on hydrogen flaking in AMS-4340 ultra-high-strength steels

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International Journal of Minerals,Metallurgy and Materials 2019年第5期26卷 611-621页

作者： Shivraj Singh Kasana O.p.pandey School of physics and Materials Science Thapar Institute of Engineering and Technology Star Wire (India) Ltd.Ballabgarh

Hydrogen flakes and elemental segregation are the main causes of steel rejection. To eliminate hydrogen flaking, the present study focuses on the manufacture of AMS-4340 ultra-high-strength steel through an alternate route. AMS-4340 was prepared using three different processing routes. The primary processing route consisted of melting in an electric arc furnace, refining in a ladle refining furnace, and vacuum degassing. After primary processing, the heat processes(D1, D2, and D3) were cast into cylindrical electrodes. For secondary processing, electroslag remelting(ESr) was carried out on the primary heats to obtain four secondary heats: E1, E2, E3, and E4. Homogenization of ingots E1, E2, E3, and E4 was carried out at 1220°C for 14, 12, 12, and 30 h, respectively, followed by an antiflaking treatment at 680°C and air cooling. In addition, the semi-finished ESr ingot E4 was again homogenized at 1220°C for 6–8 h and a second antiflaking treatment was performed at 680°C for 130 h followed by air cooling. The chemical segregation of each heat was monitored through a spectroscopy technique. The least segregation was observed for heat E4. Macrostructure examination revealed the presence of hydrogen flakes in heats E1, E2, and E3, whereas no hydrogen flakes were observed in heat E4. Ultrasonic testing revealed no internal defects in heat E4, whereas internal defects were observed in the other heats. A grain size investigation revealed a finer grain size for E4 compared with those for the other heats. Steel produced in heat E4 also exhibited superior mechanical properties. Therefore, the processing route used for heat E4 can be used to manufacture an AMS-4340 ultra-high-strength steel with superior properties compared with those of AMS-4340 prepared by the other investigated routes.

关键词： AMS-4340 steel segregation and homogenization antiflaking treatment electroslag remelting