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1.
Sci Rep ; 14(1): 15810, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982132

ABSTRACT

Multisystemic inflammatory syndrome in children (MIS-C) might manifest in a broad spectrum of clinical scenarios, ranging from mild features to multi-organ dysfunction and mortality. However, this novel entity has a heterogenicity of data regarding prognostic factors associated with severe outcomes. The present study aimed to identify independent predictors for severity by using multivariate regression models. A total of 391 patients (255 boys and 136 girls) were admitted to Vietnam National Children's Hospital from January 2022 to June 2023. The median age was 85 (range: 2-188) months, and only 12 (3.1%) patients had comorbidities. 161 (41.2%) patients required PICU admission, and the median PICU LOS was 4 (2-7) days. We observed independent factors related to PICU admission, including CRP ≥ 50 (mg/L) (OR 2.52, 95% CI 1.39-4.56, p = 0.002), albumin ≤ 30 (g/L) (OR 3.18, 95% CI 1.63-6.02, p = 0.001), absolute lymphocyte count ≤ 2 (× 109/L) (OR 2.18, 95% CI 1.29-3.71, p = 0.004), ferritin ≥ 300 (ng/mL) (OR 2.35, 95% CI 1.38-4.01), p = 0.002), and LVEF < 60 (%) (OR 2.48, 95% CI 1.28-4.78, p = 0.007). Shock developed in 140 (35.8%) patients, especially for those decreased absolute lymphocyte ≤ 2 (× 109/L) (OR 2.48, 95% CI 1.10-5.61, p = 0.029), albumin ≤ 30 (g/L) (OR 2.53, 95% CI 1.22-5.24, p = 0.013), or LVEF < 60 (%) (OR 2.24, 95% CI 1.12-4.51, p = 0.022). In conclusion, our study emphasized that absolute lymphocyte count, serum albumin, CRP, and LVEF were independent predictors for MIS-C severity. Further well-designed investigations are required to validate their efficacy in predicting MIS-C severe cases, especially compared to other parameters. As MIS-C is a new entity and severe courses may progress aggressively, identifying high-risk patients optimizes clinicians' follow-up and management to improve disease outcomes.


Subject(s)
COVID-19 , Severity of Illness Index , Systemic Inflammatory Response Syndrome , Humans , Male , Female , Child , COVID-19/epidemiology , COVID-19/diagnosis , COVID-19/complications , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/epidemiology , Vietnam/epidemiology , Child, Preschool , Adolescent , Infant , SARS-CoV-2/isolation & purification , Prognosis , Lymphocyte Count , Intensive Care Units, Pediatric , C-Reactive Protein/analysis , C-Reactive Protein/metabolism
2.
Am Surg ; 89(11): 4872-4873, 2023 Nov.
Article in English | MEDLINE | ID: mdl-33847533

ABSTRACT

Surgeons who care for patients with active SARS-CoV-2 infection represent a unique population of health care providers whose risk of infection has not been elucidated. The objective of this study was to examine SARS-CoV-2 seroprevalence among surgeons who cared for patients with active SARS-CoV-2 infection compared to other employees within our health care system and also the general public of New Orleans. 105 surgeons at our facilities provided direct surgical care to patients with active SARS-CoV-2 infection and underwent voluntary antibody testing. 2/105 (1.9% CI .2%-6.7%) tested positive for SARS-CoV-2 antibodies. 13 343 hospital employees underwent antibody testing and 1066/13 343 (8.0% CI 7.5%-8.5%) tested positive (1.9% vs. 8.0%; P = .03). We saw a significantly lower SARS-CoV-2 seroprevalence among surgeons who directly cared for infected patients versus other hospital employees. When compared to community seroprevalence (6.9% CI 6.0%-8.0%), seroprevalence among our surgeons is also significantly lower (1.9% vs. 6.9%; P = .04).


Subject(s)
COVID-19 , Surgeons , Humans , COVID-19/epidemiology , SARS-CoV-2 , New Orleans , Pandemics , Seroepidemiologic Studies , Health Personnel , Antibodies, Viral
3.
World J Nucl Med ; 21(4): 325-328, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36398298

ABSTRACT

Talc pleurodesis, a frequently performed procedure for refractory pneumothorax or pleural effusion, induces chronic granulomatous inflammation. It can present years later with pleural thickening and markedly increased uptake on positron emission tomography/computed tomography (PET/CT), mimicking the presentation of malignancies. We present the case of a 63-year-old female with positive 18 F-fluorodeoxyglucose PET/CT 20 years after talc pleurodesis. Malignancy such as mesothelioma could not initially be ruled out. CT-guided biopsy confirmed an extensive foreign-body giant-cell reaction consistent with talc-related inflammatory change. This case highlights the need for the consideration of talcoma in the differential diagnosis of patients who undergo talc pleurodesis, and is unique in the significant timespan of 20 years between pleurodesis and positive imaging findings.

4.
Front Pediatr ; 10: 946547, 2022.
Article in English | MEDLINE | ID: mdl-35903158

ABSTRACT

Background: Indirect cardiomyocyte damage-related hyperinflammatory response is one of the key mechanisms in COVID-19-induced fulminant myocarditis. In addition to the clinical benefit of using cytokines absorption hemofiltration, the effectiveness of instituting veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support for cardiac compromise has been reported. However, current literature enunciates a paucity of available data on the effectiveness of these novel modalities. Case Presentation: We reported a 9-year-old boy with recurrent COVID-19 infection-causing fulminant myocarditis, who was treated successfully by using novel modalities of oXiris ® hemofilter continuous venovenous hemofiltration (CVVH) and VA-ECMO. The patient made a full recovery without any sequelae. Conclusion: We conclude that the novel highly-absorptive hemofilter CVVH and VA-ECMO may be effective treatment modalities in managing SARS-CoV-2-induced fulminant myocarditis. Our report highlights the need for further well-designed investigations to confirm this extrapolation.

5.
Nucleic Acids Res ; 50(W1): W108-W114, 2022 07 05.
Article in English | MEDLINE | ID: mdl-35524558

ABSTRACT

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations.


Subject(s)
Computer Simulation , Software , Humans , Bioengineering , Models, Biological , Registries , Research Personnel
6.
Mol Syst Biol ; 17(2): e9982, 2021 02.
Article in English | MEDLINE | ID: mdl-33620773

ABSTRACT

Reproducibility of scientific results is a key element of science and credibility. The lack of reproducibility across many scientific fields has emerged as an important concern. In this piece, we assess mathematical model reproducibility and propose a scorecard for improving reproducibility in this field.


Subject(s)
Systems Biology/methods , Data Curation , Humans , Models, Theoretical , Reproducibility of Results
7.
Bioinformatics ; 36(17): 4649-4654, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32573648

ABSTRACT

MOTIVATION: One of the major bottlenecks in building systems biology models is identification and estimation of model parameters for model calibration. Searching for model parameters from published literature and models is an essential, yet laborious task. RESULTS: We have developed a new service, BioModels Parameters, to facilitate search and retrieval of parameter values from the Systems Biology Markup Language models stored in BioModels. Modellers can now directly search for a model entity (e.g. a protein or drug) to retrieve the rate equations describing it; the associated parameter values (e.g. degradation rate, production rate, Kcat, Michaelis-Menten constant, etc.) and the initial concentrations. Currently, BioModels Parameters contains entries from over 84,000 reactions and 60 different taxa with cross-references. The retrieved rate equations and parameters can be used for scanning parameter ranges, model fitting and model extension. Thus, BioModels Parameters will be a valuable service for systems biology modellers. AVAILABILITY AND IMPLEMENTATION: The data are accessible via web interface and API. BioModels Parameters is free to use and is publicly available at https://www.ebi.ac.uk/biomodels/parameterSearch. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Models, Biological , Systems Biology , Software
8.
ACS Omega ; 5(13): 7096-7105, 2020 Apr 07.
Article in English | MEDLINE | ID: mdl-32280850

ABSTRACT

Rare-earth (RE) phosphates often appear as an accessory phase in igneous or metamorphic rocks; however, these rocks are composed of myriad chemical elements and nuclides that interfere with the qualitative or quantitative analyses of the RE phosphates over a range of concentrations in the absence of a pretreatment. In addition, the limit of each analytical methodology constrains the approach as well as the usefulness of the results in geoscience applications. Here, we report the specific mineral characterization of RE-containing ores from Yen Phu mine, Vietnam, using a range of state-of-the-art spectroscopic techniques in conjunction with microscopy: Mössbauer spectroscopy, infrared microspectroscopy, time-resolved laser-induced fluorescence spectroscopy (TRLFS), and scanning electron microscopy with energy-dispersive X-ray spectroscopy. Because the distribution of each element in the deposit differs, such combinatorial works are necessary and could lead to more plausible answers to questions surrounding the point of origin of RE elements. The results of our Mössbauer spectroscopic analysis indicate that the three ores sampled at different locations all contain magnetite-like, hematite-like, and iron(III) salts other than hematite. In addition, we confirmed the presence of phosphate around the grain boundary in the magnetite-like mineral phase by infrared microspectroscopic analysis. The present analytical findings of trace amounts of europium(III) using TRLFS suggest that the europium ions generate identical luminescence spectra despite being embedded in three different matrices of iron minerals. This demonstration highlights the benefits of combinatorial spectroscopic analyses to gain insights into the effects of the environment of REs on their solid-state chemistry and shows the potential utility of TRLFS as a resource mining tool. Further applications of this approach in the analytical screening of rocks and minerals are feasible.

9.
Nucleic Acids Res ; 48(D1): D407-D415, 2020 01 08.
Article in English | MEDLINE | ID: mdl-31701150

ABSTRACT

Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform allows submission of models encoded in diverse modelling formats, including SBML, CellML, PharmML, COMBINE archive, MATLAB, Mathematica, R, Python or C++. The models submitted to BioModels are curated to verify the computational representation of the biological process and the reproducibility of the simulation results in the reference publication. The curation also involves encoding models in standard formats and annotation with controlled vocabularies following MIRIAM (minimal information required in the annotation of biochemical models) guidelines. BioModels now accepts large-scale submission of auto-generated computational models. With gradual growth in content over 15 years, BioModels currently hosts about 2000 models from the published literature. With about 800 curated models, BioModels has become the world's largest repository of curated models and emerged as the third most used data resource after PubMed and Google Scholar among the scientists who use modelling in their research. Thus, BioModels benefits modellers by providing access to reliable and semantically enriched curated models in standard formats that are easy to share, reproduce and reuse.


Subject(s)
Models, Biological , Biological Science Disciplines , Conflict of Interest , Programming Languages , Software , User-Computer Interface
10.
Foot (Edinb) ; 34: 45-47, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29278836

ABSTRACT

In addition to the fibularis longus and brevis muscles, a number of anomalous muscles or tendons can arise from the lateral compartment of the leg. The authors describe a bilateral and robust fibularis digiti quinti (FDQ) tendon present in the foot of a 99-year-old female cadaver, present the incidence of this tendon in a cohort of 26 cadavers dissected by podiatric-medical students for a lower-extremity anatomy course, and discuss the anthropological and clinical significance of the findings. In these specimen, the FDQ tendon arose from the fibularis brevis tendon proximal to the lateral malleolus, but did not separate completely from the fibularis brevis tendon until passing through the inferior fibular retinaculum. On the lateral dorsum of the foot, the FDQ passed through a third fibular retinaculum formed by the fibularis tertius tendon, and inserted onto the extensor sling of the fifth digit. This case specimen is designated as an example of the fully present category. Of the 52 limbs dissected, 17 limbs (33%) showed a fully present FDQ, while 20 limbs (38%) exhibited an FDQ in a rudimentary form. Thus, 71% of the limbs showed some presence of the FDQ. Because human bipedality requires less dexterity than that of nonhuman primates in the routine use of their hindlimbs, the authors interpret the high variability of the FDQ, including its absence in many feet, as a relaxation of natural selection maintaining this trait since the divergence of humans from African apes.


Subject(s)
Ankle Joint/anatomy & histology , Foot/anatomy & histology , Tendons/anatomy & histology , Aged , Aged, 80 and over , Cadaver , Dissection , Female , Fibula/anatomy & histology , Humans , Male , Middle Aged
11.
Nucleic Acids Res ; 46(D1): D1248-D1253, 2018 01 04.
Article in English | MEDLINE | ID: mdl-29106614

ABSTRACT

BioModels serves as a central repository of mathematical models representing biological processes. It offers a platform to make mathematical models easily shareable across the systems modelling community, thereby supporting model reuse. To facilitate hosting a broader range of model formats derived from diverse modelling approaches and tools, a new infrastructure for BioModels has been developed that is available at http://www.ebi.ac.uk/biomodels. This new system allows submitting and sharing of a wide range of models with improved support for formats other than SBML. It also offers a version-control backed environment in which authors and curators can work collaboratively to curate models. This article summarises the features available in the current system and discusses the potential benefit they offer to the users over the previous system. In summary, the new portal broadens the scope of models accepted in BioModels and supports collaborative model curation which is crucial for model reproducibility and sharing.


Subject(s)
Data Curation , Models, Biological , Software , Data Collection , Data Curation/methods , Internet , User-Computer Interface
12.
Environ Sci Pollut Res Int ; 23(11): 10382-10392, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27146547

ABSTRACT

Transport and fate of perfluoro- and polyfluoroalkyl substances (PFASs) in an urban water body that receives mainly urban runoff was investigated. Water, suspended solids, and sediment samples were collected during the monsoon (wet) and inter-monsoon (dry) season at different sites and depths. Samples were analyzed for C7 to C12 perfluoroalkyl carboxylate homologues (PFCAs) (PFHpA, PFOA, PFNA, PFDA, PFUnA, PFDoA), perfluorohexane, perfluorooctane, and 6:2-fluorotelomer sulfonate (PFHxS, PFOS, and 6:2FtS, respectively), perfluorooctane sulfonamide (FOSA), N-ethyl FOSA (sulfluramid), N-ethyl sulfonamidoethanol (N-EtFOSE), and N-methyl and N-ethyl sulfonamidoacetic acid (N-EtFOSAA and N-MeFOSAA, respectively). Concentrations in wet samples were only slightly higher. The sum total PFAS (ΣPFAS) concentrations dissolved in the aqueous phase and sorbed to suspended solids (SS) ranged from 107 to 253 ng/L and 11 to 158 ng/L, respectively. PFOA, PFOS, PFNA, PFHxS, and PFDA contributed most (approximately 90 %) to the dissolved ΣPFASs. N-EtFOSA dominated the particulate PFAS burden in wet samples. K D values of PFOA and PFOS calculated from paired SS and water concentrations varied widely (1.4 to 13.7 and 1.9 to 98.9 for PFOA and PFOS, respectively). Field derived K D was significantly higher than laboratory K D suggesting hydrophobic PFASs sorbed to SS resist desorption. The ΣPFAS concentrations in the top sedimentary layer ranged from 8 to 42 µg/kg and indicated preferential accumulation of the strongly sorbing long-chain PFASs. The occurrence of the metabolites N-MeFOSAA, N-EtFOSAA and FOSA in the water column and sediments may have resulted from biological or photochemical transformations of perfluorooctane sulfonamide precursors while the absence of FOSA, N-EtFOSA and 6:2FtS in sediments was consistent with biotransformation.


Subject(s)
Fluorocarbons/chemistry , Sulfonamides/chemistry , Water Pollutants, Chemical/analysis , Alkanesulfonic Acids/analysis , Biotransformation , Environmental Monitoring , Fluorocarbons/analysis , Geologic Sediments/chemistry , Hydrocarbons, Fluorinated/analysis , Singapore , Sulfonamides/analysis , Sulfonamides/metabolism , Water Supply
13.
J Vet Pharmacol Ther ; 34(2): 142-52, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21395605

ABSTRACT

Determination and kinetics of enrofloxacin and ciprofloxacin in Tra catfish (Pangasianodon hypophthalmus) and giant freshwater prawn (Macrobrachium rosenbergii) using a liquid chromatography/mass spectrometry method. J. vet. Pharmacol. Therap. 34, 142-152. The fluoroquinolones enrofloxacin (EF) and ciprofloxacin (CF) residues were investigated in the edible tissues of two important Asian aquacultured species such as Tra catfish (Pangasianodon hypophthalmus) and giant freshwater prawn (Macrobrachium rosenbergii) using a sensitive liquid chromatography-electrospray ionization-tandem mass spectrometry method. Fish and prawn were treated with medicated feed with multiple doses of EF, in field conditions. A validation study of the analytical method was realized in terms of linearity, specificity, precision (repeatability and within-laboratory reproducibility), recovery and decision limit (CCα). The time needed before the antibiotic disappears from animal tissues or reach the maximum residue limit (MRL, 100µg/kg) was assessed. The concentration values of EF detected in Tra catfish tissue were between the MRL and 2×MRL concentrations, according to the fish density, 7days following the end of the enrofloxacin treatment (20mg/kg body weight per day, for seven consecutive days). The concentration value of ER in prawn tissue was lower than the MRL and the limit of quantification (LOQ, 14µg/kg) 5 and 7days after the stop of the EF treatment (50mg/kg body weight per day, for five consecutive days), respectively. The mean detected levels of CF was much lower in comparison with that of EF, indicating that only a small part of EF is metabolized into CF (<5%) in both Tra catfish and prawn.


Subject(s)
Anti-Infective Agents/pharmacokinetics , Catfishes/metabolism , Ciprofloxacin/pharmacokinetics , Drug Residues/analysis , Fluoroquinolones/pharmacokinetics , Palaemonidae/metabolism , Administration, Oral , Animal Feed , Animals , Chromatography, Liquid/veterinary , Ciprofloxacin/analysis , Enrofloxacin , Fluoroquinolones/analysis , Fresh Water , Mass Spectrometry/veterinary
14.
J Fish Dis ; 33(9): 717-22, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20572902

ABSTRACT

The two main diseases in the pangasius catfish industry are bacillary necrosis of Pangasianodon (BNP) and motile aeromonas septicaemia (MAS), where the aetiological agents have been identified as Edwardsiella ictaluri and Aeromonas hydrophila, respectively. In this study, apparently healthy Pangasianodon hypophthalmus were exposed to E. ictaluri, A. hydrophila or both bacterial species by intraperitoneal injection or immersion. There were 20 fish per treatment group, and the bacterial isolates used for the study were recovered from natural infections of BNP or MAS in farmed Vietnamese P. hypophthalmus. The results of the experimental infections mimicked the natural disease outbreaks reported from these pathogens in P. hypophthalmus. Furthermore, it was clearly demonstrated that E. ictaluri was only recovered from the fish exposed to the bacterium and not recovered from the animals receiving A. hydrophila.


Subject(s)
Enterobacteriaceae Infections/veterinary , Fish Diseases/pathology , Gram-Negative Bacterial Infections/veterinary , Aeromonas hydrophila , Animals , Catfishes , Edwardsiella ictaluri , Enterobacteriaceae Infections/mortality , Enterobacteriaceae Infections/pathology , Fish Diseases/mortality , Gram-Negative Bacterial Infections/mortality , Gram-Negative Bacterial Infections/pathology , Kidney/pathology , Survival Analysis
16.
J Org Chem ; 68(14): 5731-4, 2003 Jul 11.
Article in English | MEDLINE | ID: mdl-12839471

ABSTRACT

A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.


Subject(s)
Anticonvulsants/chemical synthesis , gamma-Aminobutyric Acid/analogs & derivatives , gamma-Aminobutyric Acid/chemical synthesis , Bacterial Proteins , Hydrogenation , Pregabalin , Stereoisomerism , Transcription Factors
17.
Neuroscience ; 102(1): 193-200, 2001.
Article in English | MEDLINE | ID: mdl-11226683

ABSTRACT

Neuronal axons are cellular extensions that can reach more than a meter in length. To maintain such a structure, macromolecules synthesized in cell bodies must be transported to the distal axons. Proteins associated with membranous organelles are generally transported in several fast transported groups, while cytoplasmic proteins, mostly composed of cytoskeletal proteins, are transported in slowly transported groups. Neurofilaments are a main component in the slowly transported group. Composed of three polypeptide subunits (NF-H, NF-M and NF-L), they are the most abundant cytoskeletal element in large myelinated axons. In various neurological or neurotoxic disorders, selective accumulation of neurofilaments was observed in different compartments of a neuron (cell bodies, proximal or distal axons). The underlying mechanism for this regional selectivity has been unclear. Using the classical pulse labeling method, we examined the changes in neurofilament transport velocity in transgenic mice that overexpress different neurofilament subunits. We present evidence that at least three velocities of neurofilament transport exist along peripheral motor axons. Each of these velocities was altered differently depending on which neurofilament subunit was overexpressed. We suggest that neurofilament transport in motor axons consists of multiple successive stages and that each of these stages is carried out by different transport mechanisms. These differences provide a basis for the regional deficiencies in axonal transport associated with several neurological disorders.


Subject(s)
Axonal Transport/physiology , Axons/physiology , Motor Neurons/physiology , Neurofilament Proteins/metabolism , Peripheral Nerves/physiology , Spinal Cord/physiology , Animals , Axons/ultrastructure , Methionine/pharmacology , Mice , Mice, Transgenic , Motor Neurons/cytology , Neurodegenerative Diseases/metabolism , Neurodegenerative Diseases/physiopathology , Peripheral Nerves/cytology , Spinal Cord/cytology , Sulfur Radioisotopes/pharmacology , Time Factors , Tubulin/metabolism
18.
Brain Res ; 866(1-2): 326-32, 2000 Jun 02.
Article in English | MEDLINE | ID: mdl-10825509

ABSTRACT

Neurofilaments are composed of three polypeptide subunits (NF-H, NF-M and NF-L). They are the most abundant cytoskeletal element in large myelinated axons and play a central role in development of axonal caliber. To perform this role, neurofilaments are transported from their site of synthesis, the cell bodies, to the distal axons. Previous studies showed that overexpression of NF-M in transgenic mice led to accumulation of neurofilaments in neurons and a reduction in the number of neurofilaments in axons, suggesting that axonal transport of neurofilaments was slowed. To determine whether this was the case, we measured axonal transport velocities in the wild type and transgenic mice overexpressing NF-M by the classical pulse-labeling method using 35S-methionine. We found that neurofilament transport in peripheral motor axons can be described with a model consistent with two linear velocities. Contrary to expectations, both velocities were accelerated by overexpression of NF-M. These results suggest that subunit composition in neurofilaments play a regulatory role in neurofilament transport. In addition, these results show that there are regional differences in neurofilament transport along long axons and these differences may be the basis for selective regional accumulation of neurofilaments in various neurological disorders.


Subject(s)
Axonal Transport/physiology , Neurofilament Proteins/metabolism , Animals , Female , Male , Mice , Mice, Transgenic , Motor Neurons/metabolism , Motor Neurons/ultrastructure , Neurofilament Proteins/genetics
19.
J Cell Biol ; 140(5): 1167-76, 1998 Mar 09.
Article in English | MEDLINE | ID: mdl-9490729

ABSTRACT

Dendrites play important roles in neuronal function. However, the cellular mechanism for the growth and maintenance of dendritic arborization is unclear. Neurofilaments (NFs), a major component of the neuronal cytoskeleton, are composed of three polypeptide subunits, NF-H, NF-M, and NF-L, and are abundant in large dendritic trees. By overexpressing each of the three NF subunits in transgenic mice, we altered subunit composition and found that increasing NF-H and/or NF-M inhibited dendritic arborization, whereas increasing NF-L alleviated this inhibition. Examination of cytoskeletal organization revealed that increasing NF-H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtubule (MT) network. Increasing NF-H or NF-H together with NF-M further reduced NFs from dendrites. However, these changes were reversed by elevating the level of NF-L with either NF-H or NF-M. Thus, NF-L antagonizes NF-H and NF-M in organizing the NF network and maintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons.


Subject(s)
Dendrites/physiology , Motor Neurons/physiology , Neurofilament Proteins/metabolism , Animals , Cell Size , Cytoskeleton/physiology , Mice , Mice, Transgenic , Neurofilament Proteins/biosynthesis , Neurofilament Proteins/genetics , Spinal Cord
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