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1.
Opt Express ; 30(14): 25707-25717, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36237095

RESUMO

Transporting cold atoms between interconnected vacuum chambers is an important technique for increasing the versatility of cold atom setups, particularly for those that couple atoms to photonic devices. In this report, we introduce a method where we are able to image the atoms at all points during transport via moving optical dipole trap. Cooled 87Rb atoms are transported ∼50 cm into an auxiliary vacuum chamber while being monitored with a moving-frame imaging system for which in-situ characterization of the atom transport is demonstrated. Precise positioning of the atoms near photonic devices is also tested across several tapered fibers showing an axial positioning resolution of ∼450 µm.

2.
Mitochondrial DNA B Resour ; 5(1): 633-634, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33366679

RESUMO

Iksookimia yongdokensis (Actinopterygii, Cypriniformes, Cobitidae) is known as endemic freshwater fish species in Korea. The total length of I. yongdokensis mitogenome is 16,640 bp, consisting of 13 protein-coding genes (PCGs), 22 tRNAs, 2 rRNAs, and 1 control region (D-loop). The gene arrangement and content were identical with previously recorded mitogenomes of Iksookimia species. Phylogenetic analysis using PCGs and rRNA was examined by maximum likelihood method indicated that genus Iksookimia is taxonomically not stable status according to Iksookimia species and Cobitis species were grouped together.

3.
Mitochondrial DNA B Resour ; 5(1): 856-857, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33366783

RESUMO

In this study, we determined the complete mitochondrial genome sequences of cyprinid freshwater fish, Microphysogobio jeoni, belonging to the subfamily Gobioninae in the order Cypriniformes. The complete mitogenome of M. jeoni was 16,602 bp in length and consisted of 13 protein-coding genes (PCGs), 22 tRNAs, and two rRNAs. The gene order was identical with other Microphysogobio species. The overall nucleotide composition of M. jeoni was A + T: 56.1% and G + C: 43.9%, with slightly AT bias. In the phylogenetic tree, M. jeoni and other congeneric species clearly formed a monophyletic clade, and each species distinguished against each other well.

4.
Mitochondrial DNA B Resour ; 5(1): 860-861, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33366785

RESUMO

In this study, the complete mitochondrial genome sequences of Iksookimia hugowolfeldi, Korean loach species, was determined using next-generation sequencing analysis. The complete mitogenome of I. hugowolfeldi has 16,634 bp in length and consists of 13 protein-coding genes (PCGs), 22 tRNAs, two rRNAs, and one control region (D-loop). Both gene orders and characteristics were exactly accord with mitochondrial genome of other species those belong to the family Cobitidae. Phylogenetic analysis revealed that the establishment of taxonomic relationship between Iksookimia and Cobitis has still uncompleted because of the not distinguished as monophyletic status.

5.
Mitochondrial DNA B Resour ; 5(1): 866-868, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-33366788

RESUMO

The Korean catfish, Liobagrus somjinensis, was recorded in 2010 as a new species of genus Liobagrus. The complete mitochondrial DNA sequence of L. somjinensis was sequenced by next-generation sequencing (NGS) analysis. The assembled mitogenome was 16,526 bp in length and encoded 13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs. The gene arrangement, content, and total size were clearly identical with the congeneric species, L. mediadiposalis. Phylogenetic analysis based on nucleotide dataset, consisting PCGs and rRNA genes revealed the taxonomical relationship in species level among the genus Liobagrus.

6.
Exp Neurobiol ; 29(3): 219-229, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32624506

RESUMO

Understanding brain function-related neural circuit connectivity is essential for investigating how cognitive functions are decoded in neural circuits. Trans-synaptic viral vectors are useful for identifying neural synaptic connectivity because of their ability to be transferred from transduced cells to synaptically connected cells. However, concurrent labeling of multisynaptic inputs to postsynaptic neurons is impossible with currently available trans-synaptic viral vectors. Here, we report a neural circuit tracing system that can simultaneously label postsynaptic neurons with two different markers, the expression of which is defined by presynaptic input connectivity. This system, called "cFork (see fork)", includes delivering serotype 1-packaged AAV vectors (AAV1s) containing Cre or flippase recombinase (FlpO) into two different presynaptic brain areas, and AAV5 with a dual gene expression cassette in postsynaptic neurons. Our in vitro and in vivo tests showed that selective expression of two different fluorescence proteins, EGFP and mScarlet, in postsynaptic neurons could be achieved by AAV1-mediated anterograde trans-synaptic transfer of Cre or FlpO constructs. When this tracing system was applied to the somatosensory barrel field cortex (S1BF) or striatum innervated by multiple presynaptic inputs, postsynaptic neurons defined by presynaptic inputs were simultaneously labeled with EGFP or mScarlet. Our new anterograde tracing tool may be useful for elucidating the complex multisynaptic connectivity of postsynaptic neurons regulating diverse brain functions.

7.
Mitochondrial DNA A DNA Mapp Seq Anal ; 31(6): 221-227, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32552121

RESUMO

Genus Zacco specimens collected in this study were classified genetically as five species, Zacco platypus, Z. temminckii, Z. koreanus and two unidentified species, using DNA barcoding analysis based on 655 bp of mitochondrial cytochrome c oxidase subunit I (COI) gene. Two of unidentified species (Z. sp.1 and Z. sp.2) were considered to be unrecorded or new species of genus Zacco according to genetic distances between Zacco species. In addition, we determined a natural hybrid based on polymorphic base at the diagnostic positions displayed on nuclear recombination activating gene 1 (RAG1) gene (965 bp), and estimated paternal and maternal species of natural hybrid comparing phylogenetic tree between COI and RAG1, and Z. sp.1♀ × Z. koreanus♂, Z. sp.2♀ × Z. koreanus♂ and Z. koreanus♀ × Z. sp.1♂ individuals were confirmed. The habitat of natural hybrids of Z. koreanus between Z. sp.1 and Z. sp.2 was identified as Geum and Yeongsan River, respectively. In our data, only F1 hybrid generation was identified; however, generations after F1 hybrid or backcross were not demonstrated.


Assuntos
Núcleo Celular/genética , Cyprinidae/classificação , DNA/genética , Mitocôndrias/genética , Animais , Cruzamento , Quimera , Cyprinidae/genética , Código de Barras de DNA Taxonômico , Feminino , Genes RAG-1/genética , Variação Genética , Masculino , Filogenia , República da Coreia
9.
Phys Rev Lett ; 122(6): 065303, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30822055

RESUMO

We report the experimental realization of a synthetic three-leg Hall tube with ultracold fermionic atoms in a one-dimensional optical lattice. The legs of the synthetic tube are composed of three hyperfine spin states of the atoms, and the cyclic interleg links are generated by two-photon Raman transitions between the spin states, resulting in a uniform gauge flux ϕ penetrating each side plaquette of the tube. Using quench dynamics, we investigate the band structure of the Hall tube system for a commensurate flux ϕ=2π/3. Momentum-resolved analysis of the quench dynamics reveals a critical point of band gap closing as one of the interleg coupling strengths is varied, which is consistent with a topological phase transition predicted for the Hall tube system.

10.
Phys Rev Lett ; 121(15): 150403, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30362786

RESUMO

We report the experimental realization of a cross-linked chiral ladder with ultracold fermionic atoms in a 1D optical lattice. In the ladder, the legs are formed by the orbital states of the optical lattice and the complex interleg links are generated by the orbital-changing Raman transitions that are driven by a moving lattice potential superimposed onto the optical lattice. The effective magnetic flux per ladder plaquette is tuned by the spatial periodicity of the moving lattice, and the chiral currents are observed from the asymmetric momentum distributions of the orbitals. The effect of the complex cross-links is demonstrated in quench dynamics by measuring the momentum dependence of the interorbital coupling strength. We discuss the topological phase transition of the chiral ladder system for the variations of the complex cross-links.

11.
Dement Neurocogn Disord ; 17(2): 57-65, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30906393

RESUMO

BACKGROUND AND PURPOSE: Cognitive and gait disturbance are common symptoms in Parkinson's disease (PD). Although the relationship between cognitive impairment and gait dysfunction in PD has been suggested, specific gait patterns according to cognition are not fully demonstrated yet. Therefore, the aim of this study was to investigate gait patterns in PD patients with or without cognitive impairment. METHODS: We studied 86 patients at an average of 4.8 years after diagnosis of PD. Cognitive impairment was defined as scoring 1.5 standard deviation below age- and education-specific means on the Korean version of the Mini-Mental State Examination (K-MMSE). Three-dimensional gait analysis was conducted for all patients and quantified gait parameters of temporal-spatial data were used. Relationships among cognition, demographic characteristics, clinical features, and gait pattern were evaluated. RESULTS: Cognitive impairment was observed in 41 (47.7%) patients. Compared to patients without cognitive impairment, patients with cognitive impairment displayed reduced gait speed, step length, and stride length. Among K-MMSE subcategories, "registration," "attention/calculation," and "visuospatial function" were significantly associated with speed, step length, and stride length. However, age, disease duration, Hoehn-Yahr (HY) stage, or Unified Parkinson's Disease Rating Scale (UPDRS) motor score was not significantly related to any gait analysis parameter. CONCLUSIONS: Our present study shows that cognitive impairment is associated with slow and short-stepped gait regardless of HY stage or UPDRS motor score, suggesting that cognitive impairment may serve as a surrogate marker of gait disturbance or fall in PD patients.

12.
Dement Neurocogn Disord ; 16(2): 54-55, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30906371

RESUMO

Traumatic brain injury (TBI) is common, and is often the leading cause of disability and death. Complications after TBI include increased risk for chronic central nervous system disease, such as Alzheimer's disease (AD). However, the pathophysiology relating acute injury to neurodegeneration is unclear. Here we present a case of a patient whose cognition declined after TBI, and whose 18F fluorodeoxyglucose positron emission tomography scan showed an AD pattern.

13.
Dement Neurocogn Disord ; 16(3): 78-82, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30906375

RESUMO

BACKGROUND AND PURPOSE: Neuropsychiatric symptoms (NPS) such as anxiety, depression, and delusions affect up to 90% of all patients with Alzheimer's disease (AD). NPS is associated with significant caregiver burden and patient distress. Given the severe burden of NPS in AD, it is critical to know potential modifiable risk factors of NPS in AD. This study explores the association between hypertension and NPS in patients with drug-naïve AD. METHODS: We reviewed medical records of 149 patients with AD with (n=80) and without (n=69) hypertension. NPS were assessed using the Korean version of Neuropsychiatric Inventory (K-NPI). Affective, psychotic, and behavior symptom clusters were assessed separately. RESULTS: The total score of K-NPI was not significantly different between patients with AD with and without hypertension. Among K-NPI domains, scores of depression/dysphoria (p=0.045), anxiety (p=0.022), and apathy/indifference (p=0.037) were significantly higher in patients with AD with hypertension. Systolic blood pressure (BP) was associated with higher total K-NPI and affective symptom cluster scores. Diastolic BP was associated with affective symptom cluster scores. CONCLUSIONS: Results suggest that hypertension increases risk of specific NPS in patients with AD. Among NPS, hypertension was associated with affective symptom cluster.

14.
Ann Occup Environ Med ; 28: 66, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27891240

RESUMO

BACKGROUND: Agent Orange (AO) is the code name for one of the herbicides and defoliants used in the Vietnam War. Studies conducted thus far show a significant correlation between AO and the occurrence of cardiovascular diseases. But there is little data on the association between AO and stroke, and limited studies have targeted patient groups exposed to AO. METHOD: Bohun medical center Institutional Review Board (IRB) approved the study. (ID: 341) We studied patients with acute ischemic stroke within 7 days of onset in VHS medical center and 4 other general hospitals. Among them, 91 consecutive patients with previous exposure to AO were evaluated. For controlled group, 288 patients with no history of AO exposure were chosen. RESULT: There were 49 (44.0 %) DM patient with a higher frequency in the exposure group (93 (32.3 %) in control P = 0.045). There were 6 (6.6 %) hyperlipidemia in exposure group and 69 (24.0 %) in control. (P < 0.002). Small vessel occlusion was the most common subtype (36, 39.6 %) in exposure group but in control group, the large artery atherosclesosis was (120, 41.7 %) (P = 0.014). The NIHSS of the exposure group on admission showed lower scores (median values, 2 and 4, respectively; P = 0.003). The median mRS was 1 for the exposure group and 2 for the control group, at discharge and after 3 months. After 3 months of discharge, 55 (60.4 %) in the exposure group and 171 (59.4 %) in the control group showed below mRS 1 (P = 0.001). CONCLUSION: This study targeted patients who are Vietnam veteran. There is some difference in vascular risk factors and clinical manifestations suggest AO exposure has contributed to a certain extent to the stroke.

15.
Parkinsonism Relat Disord ; 32: 54-59, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27567723

RESUMO

BACKGROUND: Hemifacial spasm (HFS) is frequently caused by vascular compression of the facial nerve. Vertebrobasilar dolichoectasia (VBDE) may cause vascular crowding in the limited space of the posterior fossa, increasing the chance of vascular compression of the facial nerve. We investigated the prevalence of VBDE in HFS. METHODS: We analyzed the presence of VBDE on 3.0 T magnetic resonance images in patients with HFS and control subjects; age, sex and hypertension were matched. Two blinded readers independently assessed the images. We evaluated the vascular risk factors, including diabetes mellitus, hyperlipidemia, ischemic heart disease, stroke, and presence of lacunes. RESULTS: A total of 310 patients with HFS and 310 control subjects were included. The prevalence of VBDE was higher in patients with HFS (48/310, 15.5%) than in controls (10/310, 3.2%), with an odds ratio (OR) of 5.82 (P < 0.001). Among patients with HFS, the presence of facial nerve compressing vessels was more frequent in dolichoectasia-positive patients (87.5%) than in dolichoectasia-negative patients (58.4%) (OR: 4.99, P < 0.001). Dolichoectasia-positive patients had a higher mean age (58.8 versus 54.8 years, P = 0.03), as well as greater frequency of hypertension (OR: 2.44, P = 0.01) and history of ischemic heart disease (OR: 5.05, P = 0.03) than their dolichoectasia-negative counterparts. CONCLUSIONS: We found that VBDE is associated with HFS in a portion of patients. Since vascular risk factors were more prevalent in dolichoectasia-positive patients, an investigation of VBDE and its risk factors may serve to prevent vascular complications.


Assuntos
Espasmo Hemifacial/epidemiologia , Insuficiência Vertebrobasilar/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Espasmo Hemifacial/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estatísticas não Paramétricas , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem
16.
Daru ; 24: 8, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26980217

RESUMO

BACKGROUND: There are still a large variety of microorganisms among aquatic animals which have not been explored for their pharmacological potential. Hence, present study was aimed to isolate and characterize a potent lactic acid bacterium from fresh water fish sample Zacco koreanus, and to confirm its pharmacological potential. METHODS: Isolation of lactic acid bacteria (LAB) from fresh water fish samples was done using serial dilution method. Biochemical identification and molecular characterization of selected LAB isolate 1I1, based on its potent antimicrobial efficacy, was accomplished using API kit and 16S rRNA gene sequencing analysis. Further, 1I1 was assessed for α-glucosidase and tyrosinase inhibitory potential as well as antiviral efficacy against highly pathogenic human influenza virus H1N1 using MDCK cell line in terms of its pharmacological potential. RESULTS: Here, we first time report isolation as well as biochemical and molecular characterization of a lactic acid bacterium Lactobacillus sakei 1I1 isolated from the intestine of a fresh water fish Z. koreanus. As a result, L. sakei 1I1 exhibited potent antimicrobial effect in vitro, and diameter of zones of inhibition of 1I1 against the tested pathogens was found in the range of 13.32 ± 0.51 to 23.16 ± 0.32 mm. Also L. sakei 1I1 at 100 mg/ml exhibited significant (p < 0.05) α-glucosidase and tyrosinase inhibitory activities by 60.69 and 72.59%, in terms of its anti-diabetic and anti-melanogenic potential, respectively. Moreover, L. sakei 1I1 displayed profound anti-cytopathic effect on MDCK cell line when treated with its ethanol extract (100 mg/ml), confirming its potent anti-viral efficacy against H1N1 influenza virus. CONCLUSIONS: These findings reinforce the suggestions that L. sakei 1I1 isolated from the intestine of fresh water fish Z. koreanus might be a candidate of choice for using in pharmacological preparations as an effective drug.


Assuntos
Inibidores Enzimáticos/farmacologia , Peixes/microbiologia , Lactobacillus/isolamento & purificação , Lactobacillus/fisiologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Animais , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Cães , Água Doce , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Lactobacillus/genética , Células Madin Darby de Rim Canino/efeitos dos fármacos , Células Madin Darby de Rim Canino/virologia , RNA Ribossômico/análise , Análise de Sequência de RNA/métodos
17.
Front Microbiol ; 7: 2037, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28066360

RESUMO

This study was undertaken to characterize a lactic acid bacterium 4I1, isolated from the freshwater fish, Zacco koreanus. Morphological, biochemical, and molecular characterization of 4I1 revealed it to be Pediococcus pentosaceus 4I1. The cell free supernatant (CFS) of P. pentosaceus 4I1 exhibited significant (p < 0.05) antibacterial effects (inhibition zone diameters: 16.5-20.4 mm) against tested foodborne pathogenic bacteria with MIC and MBC values of 250-500 and 500-1,000 µg/mL, respectively. Further, antibacterial action of CFS of P. pentosaceus 4I1 against two selected bacteria Staphylococcus aureus KCTC-1621 and Escherichia coli O157:H7 was determined in subsequent assays. The CFS of P. pentosaceus 4I1 revealed its antibacterial action against S. aureus KCTC-1621 and E. coli O157:H7 on membrane integrity as confirmed by a reduction in cell viability, increased potassium ion release (900 and 800 mmol/L), reduced absorption at 260-nm (3.99 and 3.77 OD), and increased relative electrical conductivity (9.9 and 9.7%), respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of the CFS of P. pentosaceus 4I1 resulted in the identification of seven major compounds, which included amino acids, fatty acids and organic acids. Scanning electron microscopic-based morphological analysis further confirmed the antibacterial effect of CFS of P. pentosaceus 4I1 against S. aureus KCTC-1621 and E. coli O157:H7. In addition, the CFS of P. Pentosaceus 4I1 displayed potent inhibitory effects on biofilms formation by S. aureus KCTC-1621 and E. coli O157:H7. The study indicates the CFS of P. pentosaceus 4I1 offers an alternative means of controlling foodborne pathogens.

18.
Mol Brain ; 8: 85, 2015 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-26651479

RESUMO

BACKGROUND: Transmembrane protein 106B (TMEM106B) has been identified as a risk factor for frontotemporal lobar degeneration, which is the second most common form of progressive dementia in people under 65 years of age. Mutations in charged multivesicular body protein 2B (CHMP2B), which is involved in endosomal protein trafficking, have been found in chromosome 3-linked frontotemporal dementia. Despite the number of studies on both CHMP2B and TMEM106B in the endolysosomal pathway, little is known about the relationship between CHMP2B and TMEM106B in the endosomal/autophagy pathway. RESULTS: This study found that endogenous TMEM106B was partially sequestered in CHMP2B-positive structures, suggesting its possible involvement in endosomal sorting complexes required for transport (ESCRT)-associated pathways. The role of single nucleotide polymorphisms of TMEM106B (T185, S185, or S134N) in the ESCRT-associated pathways were characterized. The T185 and S185 variants were more localized to Rab5-/Rab7-positive endosomes compared with S134N, while all of the variants were more localized to Rab7-positive endosomes compared to Rab5-positive endosomes. T185 was more associated with CHMP2B compared to S185. Autophagic flux was slightly reduced in the T185-expressing cells compared to the control or S185-expressing cells. Moreover, T185 slightly enhanced the accumulation of EGFR, impairments in autophagic flux, and neurotoxicity that were caused by CHMP2B(Intron5) compared to S185-expressing cells. CONCLUSIONS: These findings suggest that the T185 variant functions as a risk factor in neurodegeneration with endolysosomal defects. This study provides a better understanding of pathogenic functions of TMEM106B, which is a risk factor for the progression of neurodegenerative diseases that are associated with endosomal defects in the aged brain.


Assuntos
Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Endossomos/fisiologia , Demência Frontotemporal/metabolismo , Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Neurônios/metabolismo , Polimorfismo de Nucleotídeo Único , Transporte Proteico/fisiologia , Animais , Autofagia , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/fisiologia , Endossomos/química , Éxons/genética , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Células HEK293 , Humanos , Imunoprecipitação , Íntrons/genética , Lisossomos/metabolismo , Proteínas de Membrana/genética , Camundongos , Degeneração Neural , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/patologia , Mapas de Interação de Proteínas , Proteólise , Proteínas Recombinantes de Fusão/metabolismo , Proteínas rab de Ligação ao GTP/análise , Proteínas rab5 de Ligação ao GTP/análise , proteínas de unión al GTP Rab7
19.
Exp Cell Res ; 319(13): 1998-2005, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23742895

RESUMO

Tar-DNA binding protein of 43kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Neuritos/fisiologia , Neurônios/fisiologia , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Forma Celular/genética , Sobrevivência Celular/genética , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Embrião de Mamíferos , Degeneração Lobar Frontotemporal/genética , Degeneração Lobar Frontotemporal/patologia , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos ICR , Mutação de Sentido Incorreto/fisiologia , Degeneração Neural/genética , Degeneração Neural/metabolismo , Neuritos/metabolismo , Neuritos/patologia , Neurônios/metabolismo , Neurônios/patologia , Transporte Proteico/genética
20.
Biochem Biophys Res Commun ; 421(3): 544-9, 2012 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-22521643

RESUMO

Endosomal sorting complexes required for transport (ESCRTs) regulate a key sorting step of protein trafficking between endosomal compartments in lysosomal degradation. Interestingly, mutations in charged multivesicular body protein 2B (CHMP2B), which is a core subunit of ESCRT-III, have been identified in some neurodegenerative diseases. However, the cellular pathogenesis resulting from CHMP2B missense mutations is unclear. Furthermore, little is known about their functional analysis in post-mitotic neurons. In order to examine their cellular pathogenesis, we analyzed their effects in the endo-lysosomal pathway in post-mitotic neurons. Interestingly, of the missense mutant proteins, CHMP2B(T104N) mostly accumulated in the Rab5- and Rab7-positive endosomes and caused delayed degradation of EGFR as compared to CHMP2B(WT). Furthermore, CHMP2B(T104N) showed less association with Vps4 ATPase and was avidly associated with Snf7-2, a core component of ESCRT-III, suggesting that it may cause defects in the process of dissociation from ESCRT. Of the missense variants, CHMP2B(T104N) caused prominent accumulation of autophagosomes. However, neuronal cell survival was not dramatically affected by expression of CHMP2B(T104N). These findings suggested that, from among the various missense mutants, CHMP2B(T104N) was associated with relatively mild cellular pathogenesis in post-mitotic neurons. This study provided a better understanding of the cellular pathogenesis of neurodegenerative diseases associated with various missense mutations of CHMP2B as well as endocytic defects.


Assuntos
Autofagia , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Lisossomos/metabolismo , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , ATPases Associadas a Diversas Atividades Celulares , Adenosina Trifosfatases/metabolismo , Sobrevivência Celular , Células Cultivadas , Receptores ErbB/metabolismo , Humanos , Mitose , Mutação de Sentido Incorreto , Proteólise
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