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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

Status and prospects for symmetric organic redox flow batteries

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journal of energy chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan c.Adam Dyker Department of chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

comparisons of oxbow lake fish assemblages in relation to bigheaded carp establishment in the lower White River, Arkansas

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ecological Processes 2024年第1期13卷 188-205页

作者： Michael A.eggleton cody j.Salzmann joseph e.Kaiser Shannon c.F.smith Department of Aquaculture and Fisheries University of Arkansas at Pine Bluff Arkansas Game and Fish commission Virginia Institute of Marine Science

Background Since the late 1990s, bigheaded carps(largely silver carp [Hypophthalmichthys molitrix] but also bighead carp [H. nobilis]) have established throughout the lower Mississippi River basin. Using previously studied oxbow lakes in the lower White River basin, Arkansas, we compared current(2017, “post-carp” establishment) fish assemblages to historical(2002, “pre-carp” establishment) fish assemblages. Fish assemblages were comprehensively assessed using multiple gears, including boat electrofishing, mini-fyke nets, and experimental small-mesh gill *** T-tests suggested that fish assemblage indices of richness, diversity, evenness, and dominance were often greater(P e post-carp period as reflected by boat electrofishing and experimental gill nets. However, all indices were generally similar(P > 0.05) between the pre-carp and post-carp period with fish assemblages depicted using mini-fyke nets. Nonmetric multidimensional scaling analyses indicated that fish assemblages differed structurally between pre-carp and post-carp periods. Assemblage differences were linked to both small and large abundance changes for more than 20 species. Abundances of gizzard shad(Dorosoma cepedianum), emerald shiner(Notropis atherinoides), pugnose minnow(Opsopoeodus emiliae), crappies(Pomoxis spp.), bluegill(Lepomis macrochirus), orangespotted sunfish(L. humilis), and yellow bass(Morone mississippiensis) declined between the pre-carp and postcarp periods. conversely, abundances of weed shiner(N. texanus), pallid shiner(Hybopsis amnis), longear sunfish(L. megalotis), buffalofishes(Ictiobus spp.), and gars(Lepisosteus spp.) generally increased during the same *** Although not possible to conclude assemblage shifts were entirely related to bigheaded carps due to the absence of an appropriate reference system where carps did not establish, the wide establishment of these carps is one of the most pervasive changes to have occurred in the lower White

关键词： Bigheaded carp Silver carp Aquatic nuisance species Fish assemblage Oxbow lake Large river

A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon c.Daeschler Katelyn j.W.So Konstantin Feinberg Marina Manoraj jenny cheung jennifer Zhang Kaveh Mirmoeini jPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

A Model to Describe the Fracture of Porous Polygranular Graphite Subject to Neutron Damage and Radiolytic Oxidation

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computers, Materials & continua 2016年第3期51卷 163-185页

作者： G.smith e.Schlangen P.e.j.Flewitt A.G.crocker A.Hodgkins Interface Analysis centre School of PhysicsUniversity of BristolBristolBS81TLUK Faculty of civil engineering and Geosciences Delft University of TechnologyDelftNetherlands HH Wills Physics Laboratory School of PhysicsUniversity of BristolBristolBS81TLUK Physics Department University of SurreyGuildfordGU27XH AMec clean energy now AMEC Foster-WheelerWalton House404 Faraday StreetBirchwood ParkWarringtonCheshireWA36GAUK

Two linked models have been developed to explore the relationship between the amount of porosity arising in service from both radiolytic oxidation and fast neutron damage that influences both the strength and the force-displacement(load-displacement)behaviour and crack propagation in pile grade A graphite used as a nuclear reactor moderator *** models of the microstructure of the porous graphite for both unirradiated and irradiated graphite are *** form the input for the second stage,simulating fracture in lattice-type finite element models,which predicts force(load)-displacement and crack propagation *** comprising aligned filler particles,typical of needle coke,in a porous matrix have been *** purpose was to isolate the contributions of filler particles and porosity to fracture strength and crack paths and consider their implications for the overall failure of reactor core graphite.

关键词： Reactor core graphite Modelling microstructure Fe lattice model Fracture strength crack path

Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi juan Pablo de Rivero Vaccari jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang j.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

encapsulating peritoneal sclerosis

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World journal of Gastroenterology 2018年第28期24卷 3101-3111页

作者： christopher j Danford Steven c Lin Martin P smith jacqueline L Wolf Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center Harvard Medical School Department of Radiology Beth Israel Deaconess Medical Center Harvard Medical School

encapsulating peritoneal sclerosis(ePS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. ePS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for ePS involves treating the underlying condition or eliminating possible inciting agents(i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. ePSspecific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is timeconsuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease.

关键词： Abdominal cocoon Sclerosing encapsulating peritonitis Peritoneal sclerosis Peritonectomy enterolysis Peritoneal dialysis Tamoxifen corticosteroids

Variation in sexual dimorphism and assortative mating do not predict genetic divergence in the sexually dimorphic Goodeid fish Girardinichthys multiradiatus

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current Zoology 2012年第3期58卷 440-452页

作者： c. MAcIAS GARcIA G smith c. GONZALeZ ZUARTH j. A. GRAVeS M. G. RITcHIe Departamento de ecologia evolutiva Instituto de Ecologia UNAM A. E 70-275 C. E 04510 M6xico DE M6xico School of Biology University of St Andrews St Andrews Fife KY16 9TH Scotland UK

Sexual dimorphism is often used as a proxy for the intensity of sexual selection in comparative studies of sexual selection and diversification. The Mexican Goodeinae are a group of livebearing freshwater fishes with large variation between species in sexual dimorphism in body shape. Previously we found an association between variation in morphological sexual dimorphism between species and the amount of gene flow within populations in the Goodeinae. Here we have examined if mor- phological differentiation within a single dimorphic species is related to assortative mating or gene flow between populations. In the Amarillo fish Girardinichthys multiradiatus studies have shown that exaggerated male fins are targets of female preferences. We find that populations of the species differ in the level of sexual dimorphism displayed due to faster evolution of differences in male than female morphology. However, this does not predict variation in assortative mating tests in the laboratory; in fact dif- ferences in male morphology are negatively correlated with assortative mating. Microsatellite markers reveal significant genetic differences between populations. However, gene flow is not predicted by either morphological differences or assortative mating. Rather, it demonstrates a pattern of isolation by distance with greater differentiation between watersheds. We discuss the caveats of predicting behavioural and genetic divergence from so-called proxies of sexual selection [current Zoology 58 （3）： 440-452, 2012].

关键词： Sexual dimorphism Assortative mating Genetic distance Speciation Viviparous fish

GAP jUNcTIONAL INTeRceLLULAR cOMMUNIcATION (GjIc) IN RAT GLIOMA ceLLS — cHARAcTeRIZATIONS TO DeTecT INHIBITORS OF MeTABOLIc cOOPeRATION

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Science china chemistry 1990年第4期33卷 435-443页

作者：林仲翔 c.c.cHANG j.e.TROSKO Beijing Institute for cancer Research Beijing 108034 PRC Michigan State University MI USA

Gap junctional intercellular communication (GjIc) as measured by metabolic cooperation was examined in a rat glioma cell line P_(98)F_(47). X-ray induced mutants of P_(98)F_(47) cells were grown in 6-thioguanine selective medium (6TG medium) to separate 6TG-resistant HGPRT- mutant cells (6TG^r). By co-culturing 200 6TG^r cells with varied high densities of the wild type 6TG-sensitive cells (6TG^s), it was found that the recovery of 6TG^r cells depended on the density of 6TG^s cells. Higher densities of 6TG^s cells reduced the recovery of 6TG^r cells. These results demonstrate the ability of P_(98)F_(47) cells to perform metabolic cooperation which is indicative of GjIc. When metabolic cooperation was inhibited, increased recovery of 6TG^r cells was observed. Presented results also demonstrate metabolic cooperation between P_(98)F_(47) glioma cells and normal rat glial cells. effect of tumor promoting chemicals on metabolic cooperation of P_(98)F_(47) cells was studied.~3H-uridine nucleot de echnique was used to confirm the above observations. The results suggest that these cells may provide the basis for an in uitro assay specially to study brain tumor promoters and neurotoxins.

关键词： GjIc glioma glial cell metabolic cooperation.