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1.
Development ; 150(16)2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37497597

RESUMO

Morphological development of the lung requires complex signal crosstalk between the mesenchymal and epithelial progenitors. Elucidating the genetic cascades underlying signal crosstalk is essential to understanding lung morphogenesis. Here, we identified Nolz1 as a mesenchymal lineage-specific transcriptional regulator that plays a key role in lung morphogenesis. Nolz1 null mutation resulted in a severe hypoplasia phenotype, including a decreased proliferation of mesenchymal cells, aberrant differentiation of epithelial cells and defective growth of epithelial branches. Nolz1 deletion also downregulated Wnt2, Lef1, Fgf10, Gli3 and Bmp4 mRNAs. Mechanistically, Nolz1 regulates lung morphogenesis primarily through Wnt2 signaling. Loss-of-function and overexpression studies demonstrated that Nolz1 transcriptionally activated Wnt2 and downstream ß-catenin signaling to control mesenchymal cell proliferation and epithelial branching. Exogenous Wnt2 could rescue defective proliferation and epithelial branching in Nolz1 knockout lungs. Finally, we identified Fgf9 as an upstream regulator of Nolz1. Collectively, Fgf9-Nolz1-Wnt2 signaling represents a novel axis in the control of lung morphogenesis. These findings are relevant to lung tumorigenesis, in which a pathological function of Nolz1 is implicated.


Assuntos
Pulmão , Transdução de Sinais , Transdução de Sinais/fisiologia , Diferenciação Celular/genética , Células Epiteliais , Morfogênese/genética , Mesoderma , Regulação da Expressão Gênica no Desenvolvimento
2.
Langmuir ; 40(37): 19506-19516, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39205649

RESUMO

The efficacy and structural evolution of Mo-doped titania nanoparticles (MTNPs) as advanced photocatalysts for degrading methyl blue (MB) are investigated by X-ray absorption spectroscopy (XAS). The 3 wt % MTNP, characterized by uniform size and anatase structure, exhibits higher efficiency. The spectral analyses unveiled structural variations in the TiO6 octahedral structure and revealed an active site of the distorted square pyramidal structure symmetry (C4v). The in situ XAS spectra illustrate that MTNPs, particularly at 3 wt % doping, effectively enhanced the hole carriers in Ti 3d orbitals with a charge transfer to Mo 4d orbitals and impeded electron-hole pair merging, significantly enhancing the photodegradation under light illumination. This study deepens our understanding of the crucial role of Mo doping in optimizing TiO2 nanoparticle performance for efficient environmental remediation, showcasing the potential of MTNPs as sustainable photocatalytic materials.

3.
Brain ; 146(8): 3542-3557, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37137515

RESUMO

Human speech and language are among the most complex motor and cognitive abilities. The discovery of a mutation in the transcription factor FOXP2 in KE family members with speech disturbances has been a landmark example of the genetic control of vocal communication in humans. Cellular mechanisms underlying this control have remained unclear. By leveraging FOXP2 mutation/deletion mouse models, we found that the KE family FOXP2R553H mutation directly disables intracellular dynein-dynactin 'protein motors' in the striatum by induction of a disruptive high level of dynactin1 that impairs TrkB endosome trafficking, microtubule dynamics, dendritic outgrowth and electrophysiological activity in striatal neurons alongside vocalization deficits. Dynactin1 knockdown in mice carrying FOXP2R553H mutations rescued these cellular abnormalities and improved vocalization. We suggest that FOXP2 controls vocal circuit formation by regulating protein motor homeostasis in striatal neurons, and that its disruption could contribute to the pathophysiology of FOXP2 mutation/deletion-associated speech disorders.


Assuntos
Corpo Estriado , Fala , Humanos , Camundongos , Animais , Fala/fisiologia , Corpo Estriado/metabolismo , Neurônios/metabolismo , Neostriado/metabolismo , Distúrbios da Fala , Mutação/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Vocalização Animal/fisiologia
4.
Small ; 19(2): e2203881, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36404110

RESUMO

Carbon@titania yolk-shell nanostructures are successfully synthesized at different calcination conditions. These unique structure nanomaterials can be used as a photocatalyst to degrade the emerging water pollutant, acetaminophen (paracetamol). The photodegradation analysis studies have shown that the samples with residual carbon nanospheres have improved the photocatalytic efficiency. The local electronic and atomic structure of the nanostructures are analyzed by X-ray absorption spectroscopy (XAS) measurements. The spectra confirm that the hollow shell has an anatase phase structure, slight lattice distortion, and variation in Ti 3d orbital orientation. In situ XAS measurements reveal that the existence of amorphous carbon nanospheres inside the nano spherical shell inhibit the recombination of electron-hole pairs; more mobile holes are formed in the p-d hybridized bands near the Fermi surface and enables the acceleration of the carries that significantly enhance the photodegradation of paracetamol under UV-visible irradiation. The observed charge transfer process from TiO2  hybridized orbital to the carbon nanospheres reduces the recombination rate of electrons and holes, thus increasing the photocatalytic efficiency.


Assuntos
Carbono , Nanoestruturas , Fotólise , Carbono/química , Acetaminofen , Espectroscopia por Absorção de Raios X , Catálise , Nanoestruturas/química
5.
J Org Chem ; 88(13): 8441-8453, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37276376

RESUMO

Herein, we present a facile synthetic methodology to produce a range of N-(CH2-aryl/alkyl)-substituted N-(pyridin-2-yl)benzamides via palladium-mediated C(sp3)-H bond activation. The N-methyl-N-(pyridin-2-yl)benzamide precursor was first reacted with palladium(II) acetate in a stoichiometric manner to obtain the key dinuclear palladacycle intermediates, whose structures were elucidated by mass spectrometric, NMR spectroscopic, and X-ray crystallographic studies in detail. The subsequent C(sp3)-H bond functionalizations on the N-methyl group of the starting substrate show facile productions of the corresponding N-(CH2-aryl/alkyl)-substituted N-(pyridin-2-yl)benzamides with good functional group tolerance. A plausible mechanism was proposed based on density functional theory calculations in conjunction with kinetic isotope effect experiments. Finally, the synthetic transformation from the prepared N-(CH2-aryl)-N-(pyridin-2-yl)benzamides through debenzoylation to N-(CH2-aryl)-2-aminopyridine was successfully demonstrated.


Assuntos
Benzamidas , Paládio , Paládio/química , Catálise , Alquilação
6.
Proc Natl Acad Sci U S A ; 117(13): 7418-7429, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32170006

RESUMO

The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses Dlx1/2, allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of Nolz-1 and Dlx1/2 can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.


Assuntos
Gânglios da Base/citologia , Corpo Estriado/citologia , Estriado Ventral/citologia , Animais , Gânglios da Base/metabolismo , Diferenciação Celular , Corpo Estriado/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Interneurônios/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Núcleo Accumbens/citologia , Núcleo Accumbens/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Estriado Ventral/metabolismo
7.
BMC Palliat Care ; 22(1): 201, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38097993

RESUMO

BACKGROUND: Hemodialysis holds the highest incidence and prevalence rate in Taiwan globally. However, the implementation of advance care planning (ACP), advance directives (AD), and patient self-determination acts (PSDA) remains limited. Our objective was to examine the current status of ACP, AD and PSDA and potential opportunities for enhancement. METHODS: We developed a novel questionnaire to assess individuals' knowledge, attitudes, and intentions regarding ACP, AD, and PSDA. We also collected baseline characteristics and additional inquiries for correlation analysis to identify potential factors. Student's t-test and Analysis of Variance were employed to assess significance. RESULTS: Initially, a cohort of 241 patients was initially considered for inclusion in this study. Subsequently, 135 patients agreed to participate in the questionnaire study, resulting in 129 valid questionnaires. Among these respondents, 76 were male (59.9%), and 53 were female (41.1%). Only 13.2% had signed AD. A significant portion (85.3%) indicated that they had not discussed their dialysis prognosis with healthcare providers. Additionally, a mere 14% engaged in conversations about life-threatening decisions. Ninety percent believed that healthcare providers had not furnished information about ACP, and only 30% had discussed such choices with their families. The findings revealed that the average standardized score for ACP and AD goals was 84.97, while the attitude towards PSDA received a standardized score of 69.94. The intention score stood at 69.52 in standardized terms. Potential candidates for ACP initiation included individuals aged 50 to 64, possessing at least a college education, being unmarried, and having no history of diabetes. CONCLUSION: Patients undergoing hemodialysis exhibited a significant knowledge gap concerning ACP, AD, and the PSDA. Notably, a substantial number of dialytic patients had not received adequate information on these subjects. Nevertheless, they displayed a positive attitude, and a considerable proportion expressed a willingness to sign AD. It is imperative for nephrologists to take an active role in initiating ACP discussions with patients from the very beginning.


Assuntos
Planejamento Antecipado de Cuidados , Patient Self-Determination Act , Estados Unidos , Humanos , Masculino , Feminino , Intenção , Conhecimentos, Atitudes e Prática em Saúde , Diretivas Antecipadas , Diálise Renal
8.
Molecules ; 28(21)2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37959865

RESUMO

Lung cancer has a high incidence rate worldwide, necessitating the development of new drugs. Although Magnolia figo (Lour.) DC. is known for its medicinal properties, studies on its efficacy against lung cancer are lacking. This study investigated whether the supercritical fluid extract of M. figo (FMO) can induce apoptosis in A549, a human non-small-cell lung cancer cell line. The cell viability was assessed using an MTT assay. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis and flow cytometry analysis were conducted. The expression of factors was assessed through Western blotting analyses. Gas chromatography-mass spectrometry (GC-MS) was performed. The results revealed that FMO treatment exhibited cytotoxicity, demonstrating dose-dependent effects. The TUNEL analysis and flow cytometry analysis revealed that FMO induced apoptosis in A549 cells. The Western blotting analysis revealed that FMO upregulated the expression of p53 and Bax protein, and downregulated the expression of Bcl-2 protein. The GC-MS analysis revealed eight components identified in FMO. These findings indicate that FMO can induce A549 apoptosis through the p53/Bcl-2/Bax pathways, confirming the apoptotic effects of M. figo on lung cancer cells. These results highlight the potential, for the first time, of M. figo as a source for developing novel drugs for lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Magnolia , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Magnolia/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proliferação de Células
9.
Nano Lett ; 21(6): 2444-2452, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33651617

RESUMO

Silver, king among plasmonic materials, features low inelastic absorption in the visible-infrared (vis-IR) spectral region compared to other metals. In contrast, copper is commonly regarded as too lossy for actual applications. Here, we demonstrate vis-IR plasmons with quality factors >60 in long copper nanowires (NWs), as determined by electron energy-loss spectroscopy. We explain this result by noticing that most of the electromagnetic energy in these plasmons lies outside the metal, thus becoming less sensitive to inelastic absorption. Measurements for silver and copper NWs of different diameters allow us to elucidate the relative importance of radiative and nonradiative losses in plasmons spanning a wide spectral range down to <20 meV. Thermal population of such low-energy modes becomes significant and generates electron energy gains associated with plasmon absorption, rendering an experimental determination of the NW temperature. Copper is therefore emerging as an attractive, cheap, abundant material platform for high-quality plasmonics in elongated nanostructures.

10.
ScientificWorldJournal ; 2015: 164594, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26236768

RESUMO

Dimethyl phthalate (DMP) was treated via wet oxygen oxidation process (WOP). The decomposition efficiency η DMP of DMP and mineralization efficiency η TOC of total organic carbons were measured to evaluate the effects of operation parameters on the performance of WOP. The results revealed that reaction temperature T is the most affecting factor, with a higher T offering higher η DMP and η TOC as expected. The η DMP increases as rotating speed increases from 300 to 500 rpm with stirring enhancement of gas liquid mass transfer. However, it exhibits reduction effect at 700 rpm due to purging of dissolved oxygen by overstirring. Regarding the effects of pressure P T, a higher P T provides more oxygen for the forward reaction with DMP, while overhigh P T increases the absorption of gaseous products such as CO2 and decomposes short-chain hydrocarbon fragments back into the solution thus hindering the forward reaction. For the tested P T of 2.41 to 3.45 MPa, the results indicated that 2.41 MPa is appropriate. A longer reaction time of course gives better performance. At 500 rpm, 483 K, 2.41 MPa, and 180 min, the η DMP and η TOC are 93 and 36%, respectively.


Assuntos
Minerais/química , Ácidos Ftálicos/química , Água/química , Concentração de Íons de Hidrogênio , Oxirredução , Oxigênio/química , Pressão , Rotação , Soluções , Temperatura , Fatores de Tempo
11.
Langmuir ; 30(34): 10430-9, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25105822

RESUMO

This study investigates the effect of Fe(3+) on the electronic structure of nanocrystalline ceria. Systematic synchrotron X-ray absorption spectroscopy coupled with scanning transmission electron microscopy/electron energy loss spectroscopy was utilized. The oxygen vacancies can be engineered and their number varied with the degree of iron doping. Comparing the local electronic structure around Ce sites with that around Fe sites reveals two stages of defect engineering. The concentration of Ce(3+) and the distribution of defects differ between lower and higher degrees of doping. Charge is transferred between Ce and Fe when the doping level is less than 5%, but this effect is not significant at a doping level of over 5%. This transfer of charge is verified by energy loss spectroscopy. These Fe-modified ceria nanoparticles exhibit core-shell-like structures at low doping levels and this finding is consistent with the results of scanning transmission electron microscopy/electron energy loss spectroscopy. More Fe is distributed at the surface for doping levels less than 5%, whereas the homogeneity of Fe in the system increases for doping levels higher than 5%. X-ray magnetic circular dichroism spectroscopy reveals that Ce, rather than Fe, is responsible for the ferromagnetism. Interestingly, Ce(3+) is not essential for producing the ferromagnetism. The oxygen vacancies and the defect structure are suggested to be the main causes of the ferromagnetism. The charge transfer and defect structure Fe(3+)-Vo-Ce(3+) and Fe(3+)-Vo-Fe(3+) are critical for the magnetism, and the change in saturated magnetization can be understood as being caused by the competition between interactions that originate from magnetic polarons and from paired ions.

12.
Phys Chem Chem Phys ; 16(7): 3274-81, 2014 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-24413060

RESUMO

Dopant-induced structural differences and defects in Sm doped CeO2 nanoparticles (NPs) exhibiting room temperature ferromagnetism were investigated by complementary spectroscopic analysis, including X-ray Absorption Spectroscopy, Extended X-Ray Absorption Fine Structure analysis, Raman spectroscopy and atomically resolved Scanning Transmission Electron Microscopy-Electron Energy Loss Spectroscopy (STEM-EELS). The CeO2 NPs were prepared by precipitation methods with Sm/Ce ratios ranging from 0 to 0.17 and with typical sizes from 2 to 4 nanometers. These results demonstrated that the nature and the distributions of defects strongly depend on the concentrations of the dopants. Two regimes in the formation of these (Ce1-x, Smx)O2-δ NPs were observed. At lower dopant levels (x < 7%), Sm(3+) atoms mainly replace the Ce atoms in the (Ce(3+)-O(2-) vacancy) complexes which are present in ceria NPs. The dopants are unambiguously observed and localized as diluted by real space STEM-EELS spectromicroscopy done with atomic sensitivity. Nevertheless, this substitution induces a strong structural rearrangement and some Sm dopants are also observed as interstitials in association with Ce vacancies. At higher doping concentrations (x > 7%), a Sm rich phase in association with a high amount of oxygen vacancies is observed at the surface of the particles. It results in the formation of core-shell type nanoparticles with crystallographic continuities where a Sm doped CeO2-δ core is surrounded by a layer of typical (Ce0.7, Sm0.3)2O3 composition.

13.
Neuroscience ; 542: 33-46, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38354901

RESUMO

The forkhead box protein P2 (Foxp2), initially identified for its role in speech and language development, plays an important role in neural development. Previous studies investigated the function of the Foxp2 gene by deleting or mutating Foxp2 from developmental stages. Little is known about its physiological function in adult brains. Although Foxp2 has been well studied in the dorsal striatum, its function in the nucleus accumbens (NAc) of the ventral striatum remains elusive. Here, we examine the physiological function of Foxp2 in NAc of mouse brains. We conditionally knocked out Foxp2 by microinjections of AAV-EGFP-Cre viruses into the medial shell of NAc of Foxp2 floxed (cKO) mice. Immunostaining showed increased c-Fos positive cells in cKO NAc at basal levels, suggesting an abnormality in Foxp2-deficient NAc cells. Unbiased behavioral profiling of Foxp2 cKO mice showed abnormalities in limbic-associated function. Foxp2 cKO mice exhibited abnormal social novelty without preference for interaction with strangers and familiar mice. In appetitive reward learning, Foxp2 cKO mice failed to learn the time expectancy of food delivery. In fear learning, Foxp2 cKO mice exhibited abnormal increases in freezing levels in response to tone paired with foot shock during fear conditioning. The extinction of the fear response was also altered in Foxp2 cKO mice. In contrast, conditional knockout of Foxp2 in NAc did not affect locomotion, motor coordination, thermal pain sensation, anxiety- and depression-like behaviors. Collectively, our study suggests that Foxp2 has a multifaceted physiological role in NAc in the regulation of limbic function in the adult brain.


Assuntos
Aprendizagem , Núcleo Accumbens , Camundongos , Animais , Núcleo Accumbens/metabolismo , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Proteínas Repressoras/metabolismo
14.
J Ovarian Res ; 17(1): 66, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504307

RESUMO

BACKGROUND: Quiescin sulfhydryl oxidase 2 (QSOX2) is a flavin adenine dinucleotide-dependent sulfhydryl oxidase that is known to be involved in protein folding, cell growth regulation, and redox state modification through oxidative activities. Earlier studies demonstrated the tissue and cellular localization of QSOX2 in the male reproductive tract, as well as the highly-regulated mechanism of QSOX2 protein synthesis and expression through the coordinated action of testosterone and epididymal-enriched amino acid, glutamate. However, the presence and the functions of QSOX2 in female reproduction are unknown. In this study, we applied the Cre-loxP gene manipulation system to generate the heterozygous and homozygous Qsox2 knockout mice and examined its effects on ovarian function. RESULTS: We demonstrated that QSOX2 was detected in the follicle-supporting cells (granulosa and cumulus cells) of ovarian follicles of all stages but was absent in the corpus luteum, suggesting its supportive role in folliculogenesis. In comparison with reproductive organogenesis in wild-type mice, there was no difference in testicular and epididymal structure in male Qsox2 knockout; however, Qsox2 knockout disrupted the regular ovulation process in female mice as a drastic decrease in the formation of the corpus luteum was detected, and no pregnancy was achieved when mating males with homozygous Qsox2 knockout females. RNAseq analyses further revealed that Qsox2 knockout altered critical signaling pathways and genes that are responsible for maintaining ovarian functions. CONCLUSION: Our data demonstrated for the first time that Qsox2 is critical for ovarian function in mice.


Assuntos
Células da Granulosa , Oxirredutases , Tamoxifeno , Feminino , Camundongos , Masculino , Animais , Células da Granulosa/metabolismo , Tamoxifeno/farmacologia , Tamoxifeno/metabolismo , Ovário , Ovulação , Camundongos Knockout
15.
Phys Chem Chem Phys ; 15(35): 14701-7, 2013 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-23900724

RESUMO

This study reports on the electronic structure of Fe-doped CeO2 nanoparticles (NPs), determined by coupled X-ray absorption spectroscopy and X-ray emission spectroscopy. A comparison of the local electronic structure around the Ce site with that around the Fe site indicates that the Fe substitutes for the Ce. The oxygen K-edge spectra that originated from the hybridization between cerium 4f and oxygen 2p states are sensitive to the oxidation state and depend strongly on the concentration of Fe doping. The Ce M(4,5)-edges and the Fe L(2,3)-edges reveal the variations of the charge states of Ce and Fe upon doping, respectively. The band gap is further obtained from the combined absorption-emission spectrum and decreased upon Fe doping, implying Fe doping introduces vacancies. The oxygen vacancies are induced by Fe doping and the spectrum reveals the charge transfer between Fe and Ce. Fe(3+) doping has two major effects on the formation of ferromagnetism in CeO2 nanoparticles. The first, at an Fe content of below 5%, is that the formation of Fe(3+)-Vo-Ce(3+) introduces oxygen deficiencies favoring ferromagnetism. The other, at an Fe content of over 5%, is the formation of Fe(3+)-Vo-Fe(3+), which favors antiferromagnetism, reducing the Ms. The defect structures Fe(3+)-Vo-Ce(3+) and Fe(3+)-Vo-Fe(3+) are crucial to the magnetism in these NPs and the change in Ms can be described as the effect of competitive interactions of magnetic polarons and paired ions.

16.
eNeuro ; 10(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37253589

RESUMO

Synaptic modification in postnatal development is essential for the maturation of neural networks. Developmental maturation of excitatory synapses occurs at the loci of dendritic spines that are dynamically regulated by growth and pruning. Striatal spiny projection neurons (SPNs) receive excitatory input from the cerebral cortex and thalamus. SPNs of the striatonigral direct pathway (dSPNs) and SPNs of the striatopallidal indirect pathway (iSPNs) have different developmental roots and functions. The spatial and temporal dynamics of dendritic spine maturation of these two types of SPNs remain elusive. Here, we delineate the developmental trajectories of dendritic spines of dSPNs and iSPNs in the caudoputamen and nucleus accumbens (NAc). We labeled dendritic spines of SPNs by microinjecting Cre-dependent AAV-eYFP viruses into newborn Drd1-Cre or Adora2a-Cre mice, and analyzed spinogenesis at three levels, including different SPN cell types, subregions and postnatal times. In the dorsolateral striatum, spine pruning of dSPNs and iSPNs occurred at postnatal day (P)30-P50. In the dorsomedial striatum, the spine density of both dSPNs and iSPNs reached its peak between P30 and P50, and spine pruning occurred after P30 and P50, respectively, for dSPNs and iSPNs. In the NAc shell, spines of dSPNs and iSPNs were pruned after P21-P30, but no significant pruning was observed in iSPNs of lateral NAc shell. In the NAc core, the spine density of dSPNs and iSPNs reached its peak at P21 and P30, respectively, and subsequently declined. Collectively, the developmental maturation of dendritic spines in dSPNs and iSPNs follows distinct spatiotemporal trajectories in the dorsal and ventral striatum.


Assuntos
Espinhas Dendríticas , Núcleo Accumbens , Camundongos , Animais , Camundongos Transgênicos , Corpo Estriado/metabolismo , Neurônios/fisiologia
17.
Glia ; 60(3): 487-501, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22144112

RESUMO

The substantial activation of microglia in Japanese encephalitis virus (JEV)-induced Japanese encephalitis found in numerous studies demonstrates that the disease pathogenesis involves bystander damage caused by microglia-released mediators. Previously, we reported that microglia synthesized and secreted bioactive mediators with neurotoxic potential into the cultured supernatants in response to JEV infection. In this study, we found that the supernatants of JEV-infected microglia caused MK801-inhibitable neuronal damage in cultured neurons, indicating a potential excitotoxic mechanism. Infection with JEV was found to elicit the extracellular glutamate accumulation from microglia but not from neuron and astrocyte cultures. The glutaminase inhibitor 6-diazo-5-oxo-L-norleucine, cystine/glutamate antiporter inhibitor α-aminoadipic acid, and the gap junction inhibitor carbenoxolone reduced JEV infection-induced microglial glutamate release and neurotoxicity. We further demonstrated that tumor necrosis factor-alpha (TNF-α) was a key cytokine which stimulated extensive microglial glutamate release by up-regulating glutaminase expression via signals involving protein kinase C, cAMP responsive element-binding protein, and CAAT-enhancer-binding protein-beta. Although the elevated expression of excitatory amino acid transporter 1 and 2 was observed in JEV-infected cells, the glutamate uptake activity was significantly inhibited by TNF-α. The JEV infection-induced alterations, such as the extracellular glutamate release and glutamate-mediated excitoneurotoxicity, also occurred in neuron/glia cultures. Our findings support a potential link between neuroinflammation and the development of excitotoxic neuronal injury in Japanese encephalitis. The link between neuroinflammation and excitotoxic death may involve a mechanism in which TNF-α released by microglia plays a facilitory role in glutamate excitoneurotoxicity via up-regulation of glutamate synthesis and down-regulation of glutamate uptake.


Assuntos
Ácido Glutâmico/metabolismo , Neuroglia/metabolismo , Neuroglia/virologia , Transdução de Sinais/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Comunicação Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Células Cultivadas , Córtex Cerebral/citologia , Meios de Cultivo Condicionados/farmacologia , Citocinas/metabolismo , Maleato de Dizocilpina/farmacologia , Ensaio de Desvio de Mobilidade Eletroforética , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Inibidores Enzimáticos/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação Viral da Expressão Gênica , Neuroglia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética
18.
Phys Chem Chem Phys ; 13(11): 5099-104, 2011 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-21298153

RESUMO

Through monitoring the evolution of the X-ray diffraction peaks, the phase transformation of PVP-protected Ag and Au nanoparticle deposits (NPDs) on electronic substrates of Cu and Ni upon heating in air was investigated via in situ synchrotron radiation X-ray diffraction. With an increasing temperature, the broad diffraction peak of nano-sized Ag and Au particles with the original average diameters of 4.2 nm and 9.6 nm, respectively, became sharp because of particle coarsening and coalescence. Complex phase transitions among Au, Cu, AuCu(3) and CuO(x) were observed, mainly due to the negative enthalpy of mixing between Au and Cu. The interactions between NPDs and the substrates affected the shift of diffraction peaks to lower angles, caused by thermal expansion and also the temperature for the oxide formation. Compared to Au, Ag NPDs did not form intermetallic compounds with Cu and the formation of copper oxides can also be retarded mainly due to the phase separation feature of the Ag-Cu system.

19.
Front Neuroanat ; 15: 669631, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054439

RESUMO

Schizophrenia is a devastating neuropsychiatric disease with a globally 1% life-long prevalence. Clinical studies have linked Zswim6 mutations to developmental and neurological diseases, including schizophrenia. Zswim6's function remains largely unknown. Given the involvement of Zswim6 in schizophrenia and schizophrenia as a neurodevelopmental disease, it is important to understand the spatiotemporal expression pattern of Zswim6 in the developing brain. Here, we performed a comprehensive analysis of the spatiotemporal expression pattern of Zswim6 in the mouse forebrain by in situ hybridization with radioactive and non-radioactive-labeled riboprobes. Zswim6 mRNA was detected as early as E11.5 in the ventral forebrain. At E11.5-E13.5, Zswim6 was highly expressed in the lateral ganglionic eminence (LGE). The LGE consisted of two progenitor populations. Dlx+;Er81+ cells in dorsal LGE comprised progenitors of olfactory bulb interneurons, whereas Dlx+;Isl1+ progenitors in ventral LGE gave rise to striatal projection neurons. Zswim6 was not colocalized with Er81 in the dorsal LGE. In the ventral LGE, Zswim6 was colocalized with striatal progenitor marker Nolz-1. Zswim6 was highly expressed in the subventricular zone (SVZ) of LGE in which progenitors undergo the transition from proliferation to differentiation. Double labeling showed that Zswim6 was not colocalized with proliferation marker Ki67 but was colocalized with differentiation marker Tuj1 in the SVZ, suggesting Zswim6 expression in early differentiating neurons. Zswim6 was also expressed in the adjacent structures of medial and caudal ganglionic eminences (MGE, CGE) that contained progenitors of cortical interneurons. At E15.5 and E17.5, Zswim6 was expressed in several key brain regions that were involved in the pathogenesis of schizophrenia, including the striatum, cerebral cortex, hippocampus, and medial habenular nucleus. Zswim6 was persistently expressed in the postnatal brain. Cell type analysis indicated that Zswim6 mRNA was colocalized with D1R-expressing striatonigral and D2R-expressing striatopallidal neurons of the adult striatum with a higher colocalization in striatopallidal neurons. These findings are of particular interest as striatal dopamine D2 receptors are known to be involved in the pathophysiology of schizophrenia. In summary, the comprehensive analysis provides an anatomical framework for the study of Zswim6 function and Zswim6-associated neurological disorders.

20.
J Gen Virol ; 91(Pt 4): 1028-37, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20007359

RESUMO

Japanese encephalitis is characterized by profound neuronal destruction/dysfunction and concomitant microgliosis/astrogliosis. Although substantial activation of glia is observed in Japanese encephalitis virus (JEV)-induced Japanese encephalitis, the inflammatory responses and consequences of astrocytes and microglial activation after JEV infection are not fully understood. In this study, infection of cultured neurons/glia with JEV caused neuronal death and glial activation, as evidenced by morphological transformation, increased cell proliferation and elevated tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and RANTES (regulated upon activation, normal T-cell expressed and secreted) production. Replication-competent JEV caused all glial responses and neurotoxicity. However, replication-incompetent JEV lost these abilities, except for the ability to change microglial morphology. The bystander damage caused by activated glia also contributed to JEV-associated neurotoxicity. Microglia underwent morphological changes, increased cell proliferation and elevated TNF-alpha, IL-1beta, IL-6 and RANTES expression in response to JEV infection. In contrast, IL-6 and RANTES expression, but no apparent morphological changes, proliferation or TNF-alpha/IL-1beta expression, was demonstrated in JEV-infected astrocytes. Supernatants of JEV-infected microglia, but not JEV-infected astrocytes, induced glial activation and triggered neuronal death. Antibody neutralization studies revealed that TNF-alpha and IL-1beta, but not RANTES or IL-6, released by activated microglia appeared to play roles in JEV-associated neurotoxicity. In conclusion, following JEV infection, neuronal death was accompanied by concomitant microgliosis and astrogliosis, and neurotoxic mediators released by JEV-activated microglia, rather than by JEV-activated astrocytes, had the ability to amplify the microglial response and cause neuronal death.


Assuntos
Astrócitos/fisiologia , Vírus da Encefalite Japonesa (Espécie)/patogenicidade , Microglia/fisiologia , Neurônios/patologia , Animais , Morte Celular , Células Cultivadas , Citocinas/biossíntese , DNA/biossíntese , Gliose , Mediadores da Inflamação/fisiologia , Ratos , Ratos Sprague-Dawley
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