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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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Metabolite profile comparisons between ascending and descending colon tissue in healthy adults

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World journal of Gastroenterology 2020年第3期26卷 335-352页

作者： Bridget A Baxter Kristopher D Parker michael j.nosler Sangeeta Rao Rebecca Craig Catherine Seiler Elizabeth P Ryan Department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsFort CollinsCO 80523United States University of Colorado Health Gastroenterology Clinic Fort CollinsCO 80524United States Department of Clinical Sciences Colorado State UniversityFort CollinsCO 80523United States Harmony Surgery Center Fort CollinsCO 80528United States Director of Clinical Operations Harmony Surgery CenterFort CollinsCO 80523United States

BACKGROUND Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely *** study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight,overweight,and obese *** To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer *** Global,non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite *** colon tissue and stool metabolome of healthy adults(n=24)was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal *** Ascending and descending colon contained 504 host,food,and microbiotaderived metabolites from normal weight,overweight and obese adults grouped according to body mass *** acids,lipids,and nucleotides were among the chemical types that further differentiated from the stool metabolite *** weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations,whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults(P<0.05).Obese adults had trimethylamine N-oxide,endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending *** and secondary bile acids,vitamins,and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese *** There were metabolite profile differences between right-ascending and leftdescending colon tissue in healthy *** lipids and other metabolites in

关键词： Colon Ascending Descending Metabolomics Obesity Stool

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Modelling internal air systems ingas turbine engines

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航空动力学报 2007年第4期22卷 505-520页

作者： j michael Owen Department of Mechanical Engineering University of Bath

Rotating-disc systems can be used to model,experimentally and computationally,the flow and heat transfer that occur inside the internal cooling-air systems of gas turbine *** rotating-disc systems have been used successfully to simplify and understand some of the complex flows that occur in internal-air systems,and designers have used this insight to improve the cooling effectiveness,thereby increasing the engine efficiency and reducing the *** this review paper,three important cases are considered:hot-gas ingress;the pre-swirl system;and buoyancy-induced ***,or ingestion,occurs when hot gas from the mainstream gas path is ingested into the wheel-space between the turbine disc and its adjacent *** seals are fitted at the periphery of the system,and sealing flow is used to reduce or prevent ***,too much sealing air reduces the engine efficiency,and too little can cause serious overheating,resulting in damage to the turbine rim and blade *** the flow is three-dimensional and unsteady,there are encouraging signs that simple ‘orifice models’ could be used to estimate the amount of ingress into the *** a pre-swirl system,the cooling air for the gas-turbine blades is swirled by stationary nozzles,and the air is delivered to the blades via receiver holes in the rotating turbine *** the air reduces its temperature relative to the rotating blades,and the designer needs to calculate the air temperature and pressure drop in the *** designer also needs to calculate the effect of this swirling flow on the heat transfer from the turbine disc to the air,as this has a significant effect on the temperature distribution and stresses in the *** experimental and computational studies have given a better understanding of the flow and heat transfer in these ***-induced flow occurs in the cavity between two co-rotating compressor discs when the temperature of the discs is higher than

关键词：燃气涡轮机车空气动力学数学模型旋转式圆盘系统

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Water transport to the core–mantle boundary

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National Science Review 2021年第4期8卷 13-16页

作者： michael j.Walter Earth and Planets Laboratory Carnegie Institution for Science

Water can have remarkable effects when exposed to rocks at high pressures and temperatures. It can form new minerals with unique properties and often profoundly affects the physical, transport and rheological properti...

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Pico-washing:simultaneous liquid addition and removal for continuous-flow washing of microdroplets

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Microsystems & Nanoengineering 2022年第2期8卷 249-261页

作者： michael j.Siedlik David Issadore Department of Bioengineering University of PennsylvaniaPhiladelphiaPA 19104United States

Droplet microfluidics is based on a toolbox of several established unit operations,including droplet generation,incubation,mixing,pico-injection,and *** the last two decades,the development of droplet microfluidic systems,which incorporate these multiple unit operations into a workflow,has demonstrated unique capabilities in fields ranging from single-cell transcriptomic analyses to materials *** unit operation that is sorely underdeveloped in droplet microfluidics is washing,exchange of the fluid in a droplet with a different ***,we demonstrate what we name the"pico-washer,"a unit operation capable of simultaneously adding fluid to and removing fluid from droplets in flow while requiring only a small footprint on a microfluidic *** describe the fabrication strategy,device architecture,and process parameters required for stable operation of this technology,which is capable of operating with kHz droplet ***,we provide an image processing workflow to characterize the washing process with microsecond and micrometer ***,we demonstrate the potential for integrated droplet workflows by arranging two of these unit operations in series with a droplet generator,describe a design rule for stable operation of the pico-washer when integrated into a system,and validate this design rule *** anticipate that this technology will contribute to continued development of the droplet microfluidics toolbox and the realization of novel droplet-based,multistep biological and chemical assays.

关键词： operations simultaneous removing

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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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A primitive confuciusornithid bird from China and its implications for early avian flight

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Science China Earth Sciences 2008年第5期51卷 625-639页

作者： michael j. BENTON Department of Earth Sciences University of Bristol Bristol BS8 1RJ UK

Confuciusornithids, lived from 120–125 million years ago, form a basal bird group and include the oldest birds with horny beaks. Here we describe Eoconfuciusornis zhengi, gen. et sp. nov. from the Early Cretaceous Dabeigou Formatio (131 Ma) in Fengning, Hebei Province, northern China. It represents a new and, more primitive than other known, member of this group and extends the lifespan of this family to 11 Ma, the longest of any known Early Cretaceous avian lineages. Furthermore, Eoconfuciusornis and its relatives present many osteological transformations, such as the size increase of the deltopectoral crest of the humerus and the keel of the sternum, apparently an adaptation toward improved flight in the evolution of the Confuciusornithidae.

关键词： Birds Early Cretaceous confuciusornithids flight

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Reevaluating the conceptual framework for applied research on host-plant resistance

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Insect Science 2013年第3期20卷 263-272页

作者： michael j. Stout Department of Entomology Louisiana State University Agricultural Center 404 Life Sciences Building Baton Rouge LA 70803 USA

Applied research on host-plant resistance to arthropod pests has been guided over the past 60 years by a framework originally developed by Reginald Painter in his 1951 book, Insect Resistance in Crop Plants. Painter divided the ＂phenomena＂ of resistance into three ＂mechanisms,＂ nonpreference （later renamed antixenosis）, antibiosis, and tolerance. The weaknesses of this framework are discussed. In particular, this trichotomous framework does not encompass all known mechanisms of resistance, and the antixenosis and antibiosis categories are ambiguous and inseparable in practice. These features have perhaps led to a simplistic approach to understanding arthropod resistance in crop plants. A dichotomous scheme is proposed as a replacement, with a major division between resistance （plant traits that limit injury to the plant） and tolerance （plant traits that reduce amount of yield loss per unit injury）, and the resistance category subdivided into constitutive/inducible and direct/indirect subcategories. The most important benefits of adopting this dichotomous scheme are to more closely align the basic and applied literatures on plant resistance and to encourage a more mechanistic approach to studying plant resistance in crop plants. A more mechanistic approach will be needed to develop novel approaches for integrating plant resistance into pest management programs.

关键词： antibiosis antixenosis host-plant resistance integrated pest management,plant-insect interactions tolerance

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