Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 34
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Environ Res ; 252(Pt 3): 119013, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38701890

RESUMO

Both ultrasound and sludge retention time (SRT) enable the in-situ sludge reduction during wastewater treatment, but the influence of SRT on ultrasonic lysis - cryptic growth is unclear. This paper researched the influence of different SRTs on sludge lysis - cryptic growth using a sequential bio-reactor (SBR), then explained in details the changes of microorganisms in the SBR. The best SRT for sludge reduction was 30 d, and 47.29% reduction in sludge was achieved. The different SRTs changed the organic matter removal in the wastewater, and the removal rate decreased when SRT exceeded 60 d. The size of the sludge particles varied depending on the SRT, with the smallest size at SRT of 10d being 45.6 µm and the largest size at SRT of 90d being 110.0 µm. SEM showed that the sludge surface changed rough at longer SRT. FTIR and XPS showed notable effect in sludge functional group strength at SRT of 30 d. Extracellular polymeric substance (EPS) reduced the most at SRT of 30 d. The microbial communities of sludge varied with the SRT, and the unique main genus at SRT of 5, 15, 30 and 90 d were C10-SB1A, Lactococcus, Propioniciclava, Lactococcus, respectively. Furthermore, the SRT changed relative abundance of enzymes concerned with metabolism of carbon, nitrogen, and phosphorus. Similarly, SRT changed the metabolic rate, and the metabolic rate of carbon, nitrogen and phosphorus was best at SRT of 30 d.

2.
J Environ Manage ; 352: 120044, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38184867

RESUMO

The increasing contamination of water systems by antibiotics and heavy metals has become a growing concern. The intimately coupled photocatalysis and biodegradation (ICPB) approach offers a promising strategy for the effective removal of mixed pollutants. Despite some prior research on ICPB applications, the mechanism by which ICPB eliminates mixed pollutants remains unclear. In our current study, the ICPB approach achieved approximately 1.53 times the degradation rate of ciprofloxacin (CIP) and roughly 1.82 times the reduction rate of Cr (VI) compared to photocatalysis. Remarkably, after 30 days, the ICPB achieved a 96.1% CIP removal rate, and a 97.8% reduction in Cr (VI). Our investigation utilized three-dimensional fluorescence analysis and photo-electrochemical characterization to unveil the synergistic effects of photocatalysis and biodegradation in removal of CIP and Cr (VI). Incorporation of B-Bi3O4Cl (B-BOC) photocatalyst facilitated electron-hole separation, leading to production of ·O2-, ·OH, and h+ species which interacted with CIP, while electrons reduced Cr (VI). Subsequently, the photocatalytic products were biodegraded by a protective biofilm. Furthermore, we observed that CIP, acting as an electron donor, promoted the reduction of Cr (VI). The microbial communities revealed that the number of bacteria favoring pollutant removal increased during ICPB operation, leading to a significant enhancement in performance.


Assuntos
Ciprofloxacina , Poluentes Ambientais , Antibacterianos , Biodegradação Ambiental , Cromo/química , Catálise
3.
Artigo em Inglês | MEDLINE | ID: mdl-38105322

RESUMO

The Arctic region is facing growing demands for energy to support various economic activities, while also grappling with the profound impacts of climate change. Black carbon particulate matter emissions reduction is a key objective to mitigate the susceptibility of the Arctic's ecosystems to the impact of climate change. Nuclear power has been suggested as a potential source of clean energy to decarbonize maritime transport in the Arctic. However, although the operation of nuclear-powered vessels and floating nuclear power platforms in the region ensures energy security and reduces black carbon emissions, it may pose significant risks of nuclear material release and radiological accidents and raise concerns about improper radioactive waste disposal. In regulating these nuclear-powered vessels and floating nuclear power platforms in the Arctic, the existing international legal regime faced a series of challenges. This research employs a method of policy analysis to analyze these legal challenges and explores how the international community could work together to cope with the challenges that arise in the Arctic during the operation of nuclear-powered vessels and platforms for maritime decarbonization purposes.

4.
J Environ Manage ; 347: 119249, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37812897

RESUMO

The integrated photocatalysis and fluidized bed biofilm reactor (FBBR) is an attractive wastewater treatment technique for managing wastewater containing antibiotics. However, the fast recombination of photoinduced charge and low microbial activity limit the degradation and mineralization efficiency for antibiotics. To address this, we attempt to introduce magnetic field (MF) to the integrated system with B-doped Bi3O4Cl as the photocatalysts to effectively improve removal and mineralization of ciprofloxacin (CIP). As a consequence, the degradation rate reaches 96% after 40 d in integrated system with MF. The biofilm inside the integrated system with MF carrier can mineralize the photocatalytic products, thereby increasing the total organic carbon (TOC) degradation rate by more than 32%. The electrochemical experiment indicates the Lorentz force generated by MF can accelerate charge separation, increasing the electron concentration. Simultaneously, the increased amounts of electrons lead to the generation of more ·OH and ·O2-. MF addition also results in increased biomass, increased biological respiratory activity, microbial community evolution and accelerated microbial metabolism, enabling more members to biodegrade photocatalytic intermediates. Therefore, applied MF is an efficient method to enhance CIP degradation and mineralization by the integrated system.


Assuntos
Reatores Biológicos , Águas Residuárias , Antibacterianos , Ciprofloxacina , Biofilmes
5.
J Environ Manage ; 347: 119111, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37774664

RESUMO

Ultrasonication allows sludge reduction to be performed in situ during wastewater treatment, and the reflux point of the lysed sludge affects this performance. This study investigated the effects of reflux point (anaerobic stage, carbon/nitrogen (C/N) lowest stage, and aerobic stage) on sludge lysis-cryptic growth in an anaerobic/aerobic reactor and variations in the sludge and microbial community. The best reflux point occurred at the lowest C/N ratio stage, and a 50.96% reduction in excess sludge was achieved. The reflux of the lysed sludge to the aerobic stage reduced nitrogen and phosphorus removal. The reflux of the lysed sludge decreased the average sludge size, reaching 29.2 µm when reflux to the aerobic stage. Scanning electron microscopy showed that the sludge surface was unaffected by the reflux point. The Fourier-transform infrared spectrometry and X-ray photoelectron spectroscopy results showed that the most prominent variation in the intensity of the sludge functional groups occurred when the reflux was at the lowest C/N stage. The amount of extracellular polymeric substances decreased the most during reflux to the anaerobic stage. The sludge microbial communities varied with the reflux point, and the dominant phyla during reflux to the anaerobic, lowest C/N, and aerobic stages were Bacteroidetes, Firmicutes, and Bacteroidetes, respectively. Furthermore, the reflux point did not alter the metabolic pathway of sludge microorganisms but increased the number of enzymes in metabolic pathways.


Assuntos
Microbiota , Águas Residuárias , Esgotos/química , Anaerobiose , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos , Nitrogênio , Carbono
6.
RSC Adv ; 13(24): 16145-16153, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37260719

RESUMO

Long afterglow luminescent (LAL) materials can release their stored light after turning off the light irradiating on them. Because of this unique characteristic, the coupling of LAL materials and conventional semiconductors is an environmental-friendly method for supporting photocatalytic activity for environmental remediation. Currently, the exploration of "afterglow-catalysis" materials for the fabrication of around-the-clock photocatalytic systems is still in its infancy. Accordingly, herein, we summarize the application of LAL materials in photocatalytic environmental remediation and energy crisis alleviation to stimulate further motivation for the development of novel LAL materials. By discussing the works in the last five years on novel LAL materials, we anticipate the development of new materials, i.e., "afterglow-catalysis" composites, to realize waste-to-energy, even achieving industrialization.

7.
Inorg Chem ; 62(27): 10743-10761, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37352838

RESUMO

The tripodal compounds [(TMG3trphen)MII-solv](PF6)2 (M = Mn, Fe, Co; solv = MeCN, DMF) and bipodal analogues [(TMG2biphen)MII(NCMe)x](PF6)2 (x = 3 for Mn, Fe; x = 2 for Co) and [(TMG2biphen)MIICl2] have been synthesized with ligands that feature a triaryl- or diarylmethyl-amine framework and superbasic tetramethylguanidinyl residues (TMG). The dicationic M(II) sites mediate catalytic nitrene-transfer reactions between the imidoiodinane PhI═NTs (Ts = tosyl) and a panel of styrenes in MeCN to afford aziridines and low yields of imidazolines (upon MeCN insertion) with an order of productivity that favors the bipodal over the tripodal reagents and a metal preference of Fe > Co ≥ Mn. In CH2Cl2, the more acidic Fe(II) sites favor formation of 2,4-diaryl-N-tosylpyrrolidines by means of an in situ (3 + 2) cycloaddition of the initially generated 2-aryl-N-tosylaziridine with residual styrene. In the presence of ketone, 1,3-oxazolidines can be formed in practicable yields, involving a single-pot cycloaddition reaction of alkene, nitrene, and ketone (2 + 1 + 2). Mechanistic studies indicate that the most productive bipodal Fe(II) site mediates stepwise addition of nitrene to olefins to generate aziridines with good retention of stereochemistry and further enables aziridine ring opening to unmask a 1,3-zwitterion that can undergo cycloaddition with dipolarophiles (MeCN, alkene, ketone) to afford five-membered N-heterocycles.

8.
Cell Rep ; 42(7): 112691, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37354460

RESUMO

Copy-number variations (CNVs) of the human 16p11.2 genetic locus are associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, it remains largely unclear how this locus is involved in the disease pathogenesis. Doc2α is localized within this locus. Here, using in vivo and ex vivo electrophysiological and morphological approaches, we show that Doc2α-deficient mice have neuronal morphological abnormalities and defects in neural activity. Moreover, the Doc2α-deficient mice exhibit social and repetitive behavioral deficits. Furthermore, we demonstrate that Doc2α functions in behavioral and neural phenotypes through interaction with Secretagogin (SCGN). Finally, we demonstrate that SCGN functions in social/repetitive behaviors, glutamate release, and neuronal morphology of the mice through its Doc2α-interacting activity. Therefore, Doc2α likely contributes to neurodevelopmental disorders through its interaction with SCGN.


Assuntos
Transtorno do Espectro Autista , Esquizofrenia , Animais , Humanos , Camundongos , Transtorno do Espectro Autista/genética , Deleção Cromossômica , Cromossomos Humanos Par 16/genética , Variações do Número de Cópias de DNA/genética , Esquizofrenia/genética , Secretagoginas/genética , Comportamento Social
9.
Artigo em Inglês | MEDLINE | ID: mdl-36833688

RESUMO

In recent years, the use of nuclear energy as propulsion for merchant ships has been proposed as a means of promoting the transition toward maritime decarbonization and environmentally sustainable shipping. However, there are concerns that nuclear-powered merchant ships could pose risks to the marine environment in the event of accidents, such as collisions, machinery failure or damage, fire, or explosions. The current international regulatory framework for nuclear-powered merchant ships is insufficient to address these risks. This research aims to address this gap by conducting a policy analysis of the existing regulations and a critical examination of their effectiveness in addressing the environmental risks of nuclear-powered merchant ships. Through this analysis, the study identifies the shortcomings and insufficiencies in the current framework and explores potential solutions to improve it, with the goal of enhancing the international community's ability to mitigate the potential impacts of radioactive marine pollution from nuclear-propelled ships in an era of maritime decarbonization.


Assuntos
Incêndios , Energia Nuclear , Acidentes de Trabalho , Navios , Motivação
10.
J Hazard Mater ; 446: 130693, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36592558

RESUMO

Photocatalytic oxygen activation is an excellent strategy for algae control in water. However, the fast recombination of photogenerated charge and slow rate of oxygen transfer limit the reactive oxygen species generation efficiency for algae inactivation. Herein, to solve above issues, magnetic field was introduced to the BiO2-x/Bi3NbO7 system to effectively covert oxygen into reactive radicals. The electrochemical experiment and DFT calculation results indicated the charge separation could be accelerated by the Lorentz force generated by the magnetic field, resulting in increase of electron concentration. Meanwhile, the value of volumetric gas-liquid mass transfer coefficient was increased by 59.79 % with magnetic field, thus more oxygen could be reduced to superoxide radical. Photocatalytic algae inactivation rate by BiO2-x/Bi3NbO7 with magnetic field could be increased by 2.07 times than that without magnet filed. This work further extends the strategy of using magnetic field to simultaneously facilitate the charge separation and oxygen transfer rate.


Assuntos
Luz , Oxigênio , Fenômenos Físicos
11.
J Hazard Mater ; 445: 130364, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-36463742

RESUMO

Intimately coupled photocatalysis and biodegradation (ICPB) is an emerging technology that has potential applications in the degradation of bio-recalcitrant pollutants. However, the interaction principles between photocatalysts and biofilms in ICPB have not been well developed. This article covers a cooperative degradation scheme coupling photocatalysis and biodegradation for efficient degradation and mineralization of ciprofloxacin (CIP) using ICPB with B-doped Bi3O4Cl as the photocatalyst. In consequence, a removal rate of ∼95 % is reached after 40 d. The biofilms inside the ICPB carriers can mineralize the photocatalytic products, thus improving the removal rate of total organic carbon (TOC) by more than 20 %. Interior biofilms are not destroyed by CIP or photocatalysis, and they adapt to ICPB of CIP by enriching in Pseudoxanthomonas, Ferruginibacter, Clostridium, Stenotrophomonas and Comamonas and reconstructing their microbial communities using energy produced by the light-excited photoelectrons. Furthermore, this research gives new opinion into the degradation principles of the ICPB system.


Assuntos
Ciprofloxacina , Águas Residuárias , Biodegradação Ambiental , Biofilmes , Antibacterianos , Catálise
12.
Front Psychol ; 14: 1168020, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259567

RESUMO

The aim of this study is to investigate the dynamic relationship between Chinese students' emotions and stress during a strict lockdown period in a university setting and the context of a global pandemic. Dynamic structural equation modeling was used to investigate the moderating role of resilience and loneliness in this relationship. The participants consisted of 112 students. Based on loneliness and resilience measures and the intensive tracking of emotional stress over a 21-day period, the results of data analysis indicated that the students' overall levels of positive emotions were low and relatively independent of negative emotions. Negative emotions were significantly autoregressive and their baseline was closely related to the individual's overall feelings of stress and loneliness levels, fluctuating with feelings of stress. The results confirm the hypothesis that resilience helps to stabilize emotions. Individuals with low resilience may be more emotionally sensitive in confined environments, while receiving social support may help to alleviate low moods.

13.
Ocean Coast Manag ; 228: 106321, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35990780

RESUMO

COVID-19 cases on international cruise ships have attracted extensive attention from the international community as well as the world's tourism and shipping industry. This virus highlighted the plight that must be faced by cruise ships in complicated times and situations such as pandemics. The comparative method is adopted to analyze the management measures taken by the "Diamond Princess", "Costa Serena", "Westerdam" and "Grand Princess" cruises in response to the COVID-19 pandemic and then to summarize the common dilemmas faced by these cruise ships, including defects of their internal environment, unclear health-care obligations during an epidemic, weak collaboration between the parties involved and their limited performance, and widespread infodemic and unfavorable public opinion. Given these dilemmas, measures are suggested to deal with the "cruise dilemma", including establishing and defining isolation standards on boards, enhancing the capacity of international organizations, the international community's joint response to the pandemic, promoting cooperation between countries, building an effective mechanism for the broad participation of the whole society, and standardizing the release of information and reasonably guiding public social opinion.

14.
Nanotechnology ; 33(40)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35617934

RESUMO

Metal halide perovskite solar cells (PSCs) have developed rapidly in recent years, due to their high performance and low-cost solution-based fabrication process. These excellent properties are mainly attributed to the high defect tolerance of polycrystalline perovskite films. Meanwhile, these defects can also facilitate ion migration and carrier recombination, which cause the device performance and the long-term stability of PSCs to deteriorate heavily. Therefore, it is critical to passivate the defects, especially at the surfaces of perovskite grains where the defects are most concentrated due to the dangling bonds. Here we propose a surface-capping engineering (SCE) method to construct 'dangling-bond-free' surfaces for perovskite grains. Diamine iodide (methylenediammonium diiodide, MDAI2) was used to construct an electroneutral PbX6-MDA-PbX6(X = Cl, Br or I) layer at the perovskite surfaces. Compared to the monovalent FA+which can only coordinate one [PbX6]4-slab, the bivalent MDA2+can coordinate two [PbX6]4-slabs on both sides, thus realizing a dangling-bond-free surface. Solar cells based on SCE-perovskite films exhibited a higher power conversion efficiency (PCE) of 21.6%, compared with 19.9% of the control group; and maintained over 96% of its initial PCE after 13 h during the maximum power point tracking test under continuous AM1.5G illumination, whereas the control group only lasted 1.5 h. Constructing a dangling-bond-free capping layer on the grain boundary opens new avenues for the fabrication of ultralow-defect polycrystalline semiconductors, paving the way to further improve the PCE and lifetime of PSCs.

15.
Front Mol Biosci ; 8: 701826, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34557519

RESUMO

The evolutionarily conserved Hedgehog (Hh) signaling pathway is crucial for programmed cell differentiation and proliferation. Dispatched (Disp) is a 12-transmembrane protein that plays a critical role in the Hedgehog (Hh) signaling pathway by releasing the dually lipidated ligand HhN from the membrane, a prerequisite step to the downstream signaling cascade. In this study, we focus on the Disp from water bear, a primitive animal known as the most indestructible on Earth. Using a zebrafish model, we show that the water bear homolog possesses the function of Disp. We have solved its structure to a 6.5-Å resolution using single-particle cryogenic electron microscopy. Consistent with the evolutional conservation of the pathway, the water bear Disp structure is overall similar to the previously reported structures of the fruit fly and human homologs. Although not revealing much detail at this resolution, the water bear Disp shows a different conformation compared to published structures, suggesting that they represent different functional snapshots.

16.
J Med Chem ; 64(17): 12723-12737, 2021 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-34428039

RESUMO

Eukaryotes have evolved two major pathways to repair potentially lethal DNA double-strand breaks. Homologous recombination represents a precise, DNA-template-based mechanism available during the S and G2 cell cycle phase, whereas non-homologous end joining, which requires DNA-dependent protein kinase (DNA-PK), allows for fast, cell cycle-independent but less accurate DNA repair. Here, we report the discovery of BAY-8400, a novel selective inhibitor of DNA-PK. Starting from a triazoloquinoxaline, which had been identified as a hit from a screen for ataxia telangiectasia and Rad3-related protein (ATR) inhibitors with inhibitory activity against ATR, ATM, and DNA-PK, lead optimization efforts focusing on potency and selectivity led to the discovery of BAY-8400. In in vitro studies, BAY-8400 showed synergistic activity of DNA-PK inhibition with DNA damage-inducing targeted alpha therapy. Combination of PSMA-targeted thorium-227 conjugate BAY 2315497 treatment of human prostate tumor-bearing mice with BAY-8400 oral treatment increased antitumor efficacy, as compared to PSMA-targeted thorium-227 conjugate monotherapy.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Proteína Quinase Ativada por DNA/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células , Proteína Quinase Ativada por DNA/genética , Sinergismo Farmacológico , Quimioterapia Combinada , Hepatócitos/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Fosfatidilinositol 3-Quinases/genética , Ratos , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Front Cell Dev Biol ; 9: 708038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268315

RESUMO

Src is an important oncogene that plays key roles in multiple signal transduction pathways. Csk-homologous kinase (CHK) is a kinase whose molecular roles are largely uncharacterized. We previously reported expression of CHK in normal human colon cells, and decreased levels of CHK protein in colon cancer cells leads to the activation of Src (Zhu et al., 2008). However, how CHK protein expression is downregulated in colon cancer cells has been unknown. We report herein that CHK mRNA was decreased in colon cancer cells as compared to normal colon cells, and similarly in human tissues of normal colon and colon cancer. Increased levels of DNA methylation at promotor CpG islands of CHK gene were observed in colon cancer cells and human colon cancer tissues as compared to their normal healthy counterparts. Increased levels of DNA methyltransferases (DNMTs) were also observed in colon cancer cells and tissues. DNA methylation and decreased expression of CHK mRNA were inhibited by DNMT inhibitor 5-Aza-CdR. Cell proliferation, colony growth, wound healing, and Matrigel invasion were all decreased in the presence of 5-Aza-CdR. These results suggest that increased levels of DNA methylation, possibly induced by enhanced levels of DNMT, leads to decreased expression of CHK mRNA and CHK protein, promoting increased oncogenic properties in colon cancer cells.

18.
PLoS Biol ; 19(7): e3001323, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228711

RESUMO

Synaptotagmin-7 (Syt7) plays direct or redundant Ca2+ sensor roles in multiple forms of vesicle exocytosis in synapses. Here, we show that Syt7 is a redundant Ca2+ sensor with Syt1/Doc2 to drive spontaneous glutamate release, which functions uniquely to activate the postsynaptic GluN2B-containing NMDARs that significantly contribute to mental illness. In mouse hippocampal neurons lacking Syt1/Doc2, Syt7 inactivation largely diminishes spontaneous release. Using 2 approaches, including measuring Ca2+ dose response and substituting extracellular Ca2+ with Sr2+, we detect that Syt7 directly triggers spontaneous release via its Ca2+ binding motif to activate GluN2B-NMDARs. Furthermore, modifying the localization of Syt7 in the active zone still allows Syt7 to drive spontaneous release, but the GluN2B-NMDAR activity is abolished. Finally, Syt7 SNPs identified in bipolar disorder patients destroy the function of Syt7 in spontaneous release in patient iPSC-derived and mouse hippocampal neurons. Therefore, Syt7 could contribute to neuropsychiatric disorders through driving spontaneous glutamate release.


Assuntos
Transtorno Bipolar/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinaptotagminas/fisiologia , Animais , Transtorno Bipolar/genética , Cálcio/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Modelos Animais de Doenças , Predisposição Genética para Doença , Ácido Glutâmico/metabolismo , Células HEK293 , Hipocampo/citologia , Hipocampo/metabolismo , Humanos , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Sinaptotagminas/genética
19.
Structure ; 29(11): 1286-1294.e6, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34174188

RESUMO

The 12-transmembrane protein Patched (Ptc1) acts as a suppressor for Hedgehog (Hh) signaling by depleting sterols in the cytoplasmic membrane leaflet that are required for the activation of downstream regulators. The positive modulator Hh inhibits Ptc1's transporter function by binding to Ptc1 and its co-receptors, which are locally concentrated in invaginated microdomains known as caveolae. Here, we reconstitute the mouse Ptc1 into lipid nanodiscs and determine its structure using single-particle cryoelectron microscopy. The structure is overall similar to those in amphipol and detergents but displays various conformational differences in the transmembrane region. Although most particles show monomers, we observe Ptc1 dimers with distinct interaction patterns and different membrane curvatures, some of which are reminiscent of caveolae. We find that an extramembranous "hand-shake" region rich in hydrophobic and aromatic residues mediates inter-Ptc1 interactions under different membrane curvatures. Our data provide a plausible framework for Ptc1 clustering in the highly curved caveolae.


Assuntos
Cavéolas/metabolismo , Membrana Celular/metabolismo , Proteínas Hedgehog/metabolismo , Lipídeos , Receptor Patched-1/metabolismo , Animais , Microscopia Crioeletrônica , Camundongos , Transdução de Sinais/fisiologia
20.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33782126

RESUMO

microRNA-218 (miR-218) has been linked to several cognition related neurodegenerative and neuropsychiatric disorders. However, whether miR-218 plays a direct role in cognitive functions remains unknown. Here, using the miR-218 knockout (KO) mouse model and the sponge/overexpression approaches, we showed that miR-218-2 but not miR-218-1 could bidirectionally regulate the contextual and spatial memory in the mice. Furthermore, miR-218-2 deficiency induced deficits in the morphology and presynaptic neurotransmitter release in the hippocampus to impair the long term potentiation. Combining the RNA sequencing analysis and luciferase reporter assay, we identified complement component 3 (C3) as a main target gene of miR-218 in the hippocampus to regulate the presynaptic functions. Finally, we showed that restoring the C3 activity in the miR-218-2 KO mice could rescue the synaptic and learning deficits. Therefore, miR-218-2 played an important role in the cognitive functions of mice through C3, which can be a mechanism for the defective cognition of miR-218 related neuronal disorders.


Assuntos
Complemento C3/genética , Hipocampo/metabolismo , Potenciação de Longa Duração , MicroRNAs/metabolismo , Vesículas Sinápticas/metabolismo , Regiões 3' não Traduzidas , Animais , Células Cultivadas , Complemento C3/metabolismo , Exocitose , Hipocampo/citologia , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Neurônios/metabolismo , Neurônios/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...