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1.
PLoS Biol ; 21(7): e3002210, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37486945

RESUMO

1p32.3 microdeletion/duplication is implicated in many neurodevelopmental disorders-like phenotypes such as developmental delay, intellectual disability, autism, macro/microcephaly, and dysmorphic features. The 1p32.3 chromosomal region harbors several genes critical for development; however, their validation and characterization remain inadequate. One such gene is the single-stranded DNA-binding protein 3 (SSBP3) and its Drosophila melanogaster ortholog is called sequence-specific single-stranded DNA-binding protein (Ssdp). Here, we investigated consequences of Ssdp manipulations on neurodevelopment, gene expression, physiological function, and autism-associated behaviors using Drosophila models. We found that SSBP3 and Ssdp are expressed in excitatory neurons in the brain. Ssdp overexpression caused morphological alterations in Drosophila wing, mechanosensory bristles, and head. Ssdp manipulations also affected the neuropil brain volume and glial cell number in larvae and adult flies. Moreover, Ssdp overexpression led to differential changes in synaptic density in specific brain regions. We observed decreased levels of armadillo in the heads of Ssdp overexpressing flies, as well as a decrease in armadillo and wingless expression in the larval wing discs, implicating the involvement of the canonical Wnt signaling pathway in Ssdp functionality. RNA sequencing revealed perturbation of oxidative stress-related pathways in heads of Ssdp overexpressing flies. Furthermore, Ssdp overexpressing brains showed enhanced reactive oxygen species (ROS), altered neuronal mitochondrial morphology, and up-regulated fission and fusion genes. Flies with elevated levels of Ssdp exhibited heightened anxiety-like behavior, altered decisiveness, defective sensory perception and habituation, abnormal social interaction, and feeding defects, which were phenocopied in the pan-neuronal Ssdp knockdown flies, suggesting that Ssdp is dosage sensitive. Partial rescue of behavioral defects was observed upon normalization of Ssdp levels. Notably, Ssdp knockdown exclusively in adult flies did not produce behavioral and functional defects. Finally, we show that optogenetic manipulation of Ssdp-expressing neurons altered autism-associated behaviors. Collectively, our findings provide evidence that Ssdp, a dosage-sensitive gene in the 1p32.3 chromosomal region, is associated with various anatomical, physiological, and behavioral defects, which may be relevant to neurodevelopmental disorders like autism. Our study proposes SSBP3 as a critical gene in the 1p32.3 microdeletion/duplication genomic region and sheds light on the functional role of Ssdp in neurodevelopmental processes in Drosophila.


Assuntos
Transtorno Autístico , Proteínas de Drosophila , Fatores de Transcrição , Animais , Humanos , Tatus/metabolismo , Transtorno Autístico/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
2.
Sci Rep ; 13(1): 21418, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38049503

RESUMO

Zinc oxide (ZnO) nanorods and ZnO nanostructures composited with silver (Ag) and multi-walled carbon nanotubes (MWCNTs) have been synthesized by a simple impregnation-calcination method and have been shown to be suitable for use as antimicrobial agents. The preparation method used for composite materials is very simple, time-effective, and can be used for large-scale production. Several analytical techniques, including X-ray diffraction (XRD), scanning electron spectroscopy (SEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM) and Fourier transmission infrared spectroscopy (FTIR), have been used to characterize the prepared ZnO-Ag-MWCNT composite materials. The effects on structural, morphological, and antimicrobial properties of (ZnO)100-x (Ag)x nanocomposites at various weight ratios (x = 0, 5, 10, 30, and 50 wt%) have been investigated. The antimicrobial properties of ZnO composited with Ag nanoparticles and MWCNTs towards both gram-positive and gram-negative bacteria species were studied. The effect of raw MWCNTs and MWCNTs composited with ZnO and Ag on the cell morphology and chemical composition of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was studied by SEM and EDS, respectively. It was found that composite materials made of ZnO-Ag-MWCNTs exhibit greater antibacterial activities toward the microorganisms E. coli and S. aureus than ZnO-Ag, which could be beneficial for efficient antimicrobial agents in water and air treatment applications.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Nanocompostos , Nanotubos de Carbono , Óxido de Zinco , Antibacterianos/farmacologia , Antibacterianos/química , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Nanopartículas Metálicas/química , Staphylococcus aureus , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Prata/farmacologia , Prata/química , Anti-Infecciosos/farmacologia , Nanocompostos/química , Testes de Sensibilidade Microbiana
3.
Beilstein J Nanotechnol ; 11: 1608-1614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134005

RESUMO

The oxidation of Au/Ag alloy thin films using radio-frequency oxygen plasma was studied in this work. It was demonstrated that there is a phase separation occurring between silver and gold. In addition, it was shown that the preferential oxidation of silver resulted in a solid-state diffusion of silver toward the surface where it oxidized and formed nanoporous microspheres. The gold phase remaining in the film exhibited nanoporosity due to the injected vacancies at the metal/silver oxide interface. Based on the scanning transmission electron microscopy analysis coupled with energy dispersive X-ray mapping a mechanism was proposed based on solid-state diffusion and the Kirkendall effect to explain the different steps occurring during the oxidation process.

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