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1.
EMBO Rep ; 25(5): 2202-2219, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38600346

RESUMO

Neural progenitor cells within the cerebral cortex undergo a characteristic switch between symmetric self-renewing cell divisions early in development and asymmetric neurogenic divisions later. Yet, the mechanisms controlling this transition remain unclear. Previous work has shown that early but not late neural progenitor cells (NPCs) endogenously express the autism-linked transcription factor Foxp1, and both loss and gain of Foxp1 function can alter NPC activity and fate choices. Here, we show that premature loss of Foxp1 upregulates transcriptional programs regulating angiogenesis, glycolysis, and cellular responses to hypoxia. These changes coincide with a premature destabilization of HIF-1α, an elevation in HIF-1α target genes, including Vegfa in NPCs, and precocious vascular network development. In vitro experiments demonstrate that stabilization of HIF-1α in Foxp1-deficient NPCs rescues the premature differentiation phenotype and restores NPC maintenance. Our data indicate that the endogenous decline in Foxp1 expression activates the HIF-1α transcriptional program leading to changes in the tissue environment adjacent to NPCs, which, in turn, might alter their self-renewal and neurogenic capacities.


Assuntos
Córtex Cerebral , Fatores de Transcrição Forkhead , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células-Tronco Neurais , Proteínas Repressoras , Transdução de Sinais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Animais , Camundongos , Córtex Cerebral/metabolismo , Córtex Cerebral/citologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Neovascularização Fisiológica/genética , Diferenciação Celular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Neurogênese/genética , Glicólise , Angiogênese
2.
Small ; : e2402482, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855997

RESUMO

Hydrogel as a solar evaporator shows great potential in freshwater production. However, hydrogels often lead to an imbalance between solar energy input and water supply management due to their excessively high saturated water content. Thus, achieving a stable water-energy-balance in hydrogel evaporators remains challenging. Here, by tortuosity engineering designed water transport channels, a seamless high-tortuosity/low-tortuosity/high-tortuosity structured hydrogel (SHLH structure hydrogel) evaporator is developed, which enables the hydrogel with customized water transport rate, leading to the controlled water supply at the evaporator interface. An excellent equilibrium between the photothermal conversion and water supply is established, and the maximum utilization of solar energy is realized, thereby achieving an excellent evaporation rate of 3.64 kg m-2 h-1 under one solar illumination. This tortuosity engineering controlled SHLH structured evaporator provides a novel strategy to attain water-energy-balance and expands new approaches for constructing hydrogel-based evaporators with tailored water transportation capacity.

3.
Am J Med Genet A ; : e63790, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922739

RESUMO

A 7-month-old boy presented to our clinic with developmental delay, Magnetic Resonance Imaging (MRI) features of delayed myelination and diffusion restriction, and a homozygous variant of uncertain significance (c.4T>G, p.Phe2Val) in HIKESHI, a gene associated with autosomal-recessive hypomyelinating leukodystrophy 13. We hypothesized that the variant is disease-causing and aimed to rescue the cellular phenotype with vector-mediated gene replacement. HIKESHI mediates heat-induced nuclear accumulation of heat-shock proteins, including HSP70, to protect cells from stress. We generated skin fibroblasts from the proband and proband's mother (heterozygous) to compare protein expression and subcellular localization of HSP70 under heat stress conditions, and the effect of vector-mediated overexpression of HIKESHI in the proband's cells under the same heat stress conditions. Western blot analysis revealed absent HIKESHI protein from proband fibroblasts, contrasted with ample expression in parental cells. Under heat stress conditions, while the mother's cells displayed appropriate nuclear localization of HSP70, the proband's cells displayed impaired nuclear translocalization. When patient fibroblasts were provided exogenous HIKESHI, the transfected proband's cells showed restored heat-induced nuclear translocalization of HSP70 under conditions of heat stress. These functional data establish that the patient's variant is a pathogenic loss-of-function mutation, thus confirming a diagnosis of hypomyelinating leukodystrophy 13 and that vector-mediated gene replacement may be an effective treatment approach for patients with this disorder.

4.
Thromb J ; 21(1): 75, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37430265

RESUMO

BACKGROUND: Contemporary data regarding the clinical characteristics and prognosis of left ventricular thrombus (LVT) in older adults (aged ≥ 65 years old) are lacking. In this study, we characterized elderly patients with LVT (aged ≥ 65 years old) and investigated the long-term prognosis in this highly vulnerable patient population. METHODS: This single-center, retrospective study was conducted from January 2017 to December 2022. Patients with a reported LVT were assessed primarily by transthoracic echocardiography (TEE) and classified into two groups: elderly LVT groups and younger LVT groups. All patients were treated with anticoagulant treatment. Major adverse cardiovascular event (MACE) was defined as the composite of all-cause mortality, systemic embolism, and rehospitalization for cardiovascular events. Survival analyses were performed with the Kaplan-Meier method and Cox proportional-hazard model. RESULTS: A total of 315 eligible patients were included. Compared to the younger LVT group (n = 171), the elderly LVT group (n = 144) had a lower proportion of males and lower serum creatinine clearance, as well as a higher level of NT-proBNP, and a higher rate of history of systemic embolism. LVT resolution occurred in 59.7% and 69.0% of patients in the elderly LVT group and younger LVT group, respectively, with no significant difference (adjusted HR, 0.97; 95% CI, 0.74-1.28; P = 0.836). Yet, elderly patients with LVT, had higher prevalence rates of MACE (adjusted HR, 1.52; 95% CI, 1.10-2.11; P = 0.012), systemic embolism (adjusted HR, 2.81; 95% CI, 1.20-6.59; P = 0.017) and all-cause mortality (adjusted HR, 2.20; 95% CI, 1.29-3.74; P = 0.004) compared with younger patients with LVT. After adjusting for mortality in the Fine-Gray model, similar results were observed. Additionally, patients treated with different anticoagulation therapies (DOACs vs. warfarin) achieved a similar improvement in prognosis (P > 0.05) or LVT resolution (P > 0.05) in elderly patients with LVT. CONCLUSIONS: Our results found that elderly patients experiencing LVT have a poor prognosis compared with the younger ones. Clinical prognosis in elderly patients did not significantly differ with the type of anticoagulant used. With aging societies worldwide, further evidence of antithrombotic therapy in elderly individuals with LVT is necessary.

5.
Development ; 145(6)2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-29487109

RESUMO

The primary cilium is a microtubule-based organelle required for Hedgehog (Hh) signaling and consists of a basal body, a ciliary axoneme and a compartment between the first two structures, called the transition zone (TZ). The TZ serves as a gatekeeper to control protein composition in cilia, but less is known about its role in ciliary bud formation. Here, we show that centrosomal protein Dzip1l is required for Hh signaling between Smoothened and Sufu. Dzip1l colocalizes with basal body appendage proteins and Rpgrip1l, a TZ protein. Loss of Dzip1l results in reduced ciliogenesis and dysmorphic cilia in vivo Dzip1l interacts with, and acts upstream of, Cby, an appendage protein, in ciliogenesis. Dzip1l also has overlapping functions with Bromi (Tbc1d32) in ciliogenesis, cilia morphogenesis and neural tube patterning. Loss of Dzip1l arrests ciliogenesis at the stage of ciliary bud formation from the TZ. Consistent with this, Dzip1l mutant cells fail to remove the capping protein Cp110 (Ccp110) from the distal end of mother centrioles and to recruit Rpgrip1l to the TZ. Therefore, Dzip1l promotes ciliary bud formation and is required for the integrity of the TZ.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Transporte/metabolismo , Cílios/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Padronização Corporal/genética , Técnicas de Cultura de Células , Centríolos/metabolismo , Cílios/fisiologia , Imunofluorescência , Camundongos , Organogênese/genética , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
6.
BMC Neurol ; 21(1): 191, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975565

RESUMO

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and poor prognostics in acute ischemic stroke (AIS) patients who receive intravenous thrombolysis (IVT) remains controversial. The purpose of this systematic review and meta-analysis was to evaluate the association between the NLR and poor prognosis after IVT. Furthermore, we aimed to determine whether the NLR at admission or post-IVT plays a role in AIS patients who received IVT. METHODS: The PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if they were related to the NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data. RESULTS: Twelve studies, including 3641 patients, met the predefined inclusion criteria. Higher NLRs were associated with an increased risk of hemorrhagic transformation (HT) (OR = 1.33, 95 % CI = 1.14-1.56, P < 0.001) and a poor 3-month functional outcome (OR = 1.64, 95 % CI = 1.38-1.94, P < 0.001) in AIS patients who received IVT. Subgroup analysis suggested that the NLR at admission rather than post-IVT was associated with a higher risk of HT (OR = 1.33, 95 % CI = 1.01-1.75, P = 0.039). There was no statistically significant difference between higher NLRs and 3-month mortality (OR = 1.14, 95 % CI = 0.97-1.35, P = 0.120). CONCLUSIONS: A high NLR can predict HT and poor 3-month functional outcomes in AIS patients who receive IVT. The NLR at admission rather than the post-IVT NLR was an independent risk factor for an increased risk of HT after IVT.


Assuntos
AVC Isquêmico/sangue , AVC Isquêmico/tratamento farmacológico , Linfócitos , Neutrófilos , Estudos de Casos e Controles , China , Estudos de Coortes , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Contagem de Linfócitos , Prognóstico , Fatores de Risco , Terapia Trombolítica/métodos
7.
BMC Cardiovasc Disord ; 20(1): 428, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993501

RESUMO

BACKGROUND: The predictors of left ventricular thrombus (LVT) formation are not well defined in the contemporary era, especially in those patients at high risk. We aimed to evaluate whether the platelet/lymphocyte ratio (PLR) is valuable in the determination of LVT formation in patients with anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. METHODS: The LVT group (n = 46) was identified from anterior STEMI patients with LV dysfunction who were treated with primary percutaneous coronary intervention (PCI) from January 2017 to December 2019 at the China-Japan Union Hospital of Jilin University. The no-LVT group (n = 92) were also selected from the same batch of patients and were age- and sex-matched to the patients with LVT. The PLR was determined at admission and was calculated as the ratio of the platelet count to the lymphocyte count using the complete blood count. The presence of LVT was determined by echocardiography. RESULTS: The PLR were significantly higher in patients with LVT than in no-LVT group (p = 0.001). In a receiver operator characteristic curve (ROC) analysis, using a cut-off value of 118.07 (AUC 0.673, 95% CI: 0.574-0.771, P = 0.001), the PLR could independently predict the occurrence of LVT. Multivariate analysis showed that an increased PLR (OR = 1.011, 95% CI: 1.004-1.018, P = 0.002), the presence of a left ventricular aneurysm (OR = 46.350, 95% CI: 5.659-379.615, P < 0.001) and increased DTBT (OR = 1.005, 95% CI: 1.001-1.009, P = 0.012) were independent predictors of LVT formation. CONCLUSIONS: In acute anterior STEMI patients with LV dysfunction, an increased PLR and DTBT and the presence of an LV aneurysm were independent predictors of LVT formation. A larger prospective study is warranted to evaluate this result. TRIAL REGISTRATION: This study was registered (May 4, 2019) on Chinese Clinical Trial Registry ( ChiCTR-DDD-17011214 ).


Assuntos
Infarto Miocárdico de Parede Anterior/terapia , Plaquetas , Linfócitos , Intervenção Coronária Percutânea , Trombose/etiologia , Disfunção Ventricular Esquerda/etiologia , Idoso , Infarto Miocárdico de Parede Anterior/sangue , Infarto Miocárdico de Parede Anterior/complicações , Infarto Miocárdico de Parede Anterior/diagnóstico por imagem , Feminino , Aneurisma Cardíaco/complicações , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Contagem de Plaquetas , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Trombose/diagnóstico por imagem , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda
8.
Dev Biol ; 430(1): 156-165, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28800946

RESUMO

Tctn1, Tctn2, and Tctn3 are membrane proteins that localize at the transition zone of primary cilia. Tctn1 and Tctn2 mutations have been reported in both humans and mice, but Tctn3 mutations have been reported only in humans. It is also not clear whether the three Tctn proteins are functionally conserved with respect to ciliogenesis and Hedgehog (Hh) signaling. In the present study, we report that loss of Tctn3 gene function in mice results in a decrease in ciliogenesis and Hh signaling. Consistent with this, Tctn3 mutant mice exhibit holoprosencephaly and randomized heart looping and lack the floor plate in the neural tube, the phenotypes similar to those of Tctn1 and Tctn2 mutants. We also show that overexpression of Tctn3, but not Tctn1 or Tctn2, can rescue ciliogenesis in Tctn3 mutant cells. Similarly, replacement of Tctn3 with Tctn1 or Tctn2 in the Tctn3 gene locus results in reduced ciliogenesis and Hh signaling, holoprosencephaly, and randomized heart looping. Surprisingly, however, the neural tube patterning and the proteolytic processing of Gli3 (a transcription regulator for Hh signaling) into a repressor, both of which are usually impaired in ciliary gene mutants, are normal. These results suggest that Tctn1, Tctn2, and Tctn3 are functionally divergent with respect to their role in ciliogenesis and Hh signaling but conserved in neural tube patterning and Gli3 processing.


Assuntos
Padronização Corporal , Cílios/metabolismo , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Tubo Neural/embriologia , Tubo Neural/metabolismo , Organogênese , Proteínas Adaptadoras de Transdução de Sinal , Animais , Proteínas Reguladoras de Apoptose , Padronização Corporal/genética , Sequência Conservada , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário , Fibroblastos/metabolismo , Deleção de Genes , Inativação Gênica , Holoprosencefalia/metabolismo , Holoprosencefalia/patologia , Homozigoto , Camundongos , Organogênese/genética , Transdução de Sinais/genética , Proteína Gli3 com Dedos de Zinco
9.
Dev Biol ; 429(1): 147-157, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28673820

RESUMO

Hedgehog (Hh) signaling is thought to occur in primary cilia, but the molecular basis of Gli2 and Gli3 activation by Hh signaling in cilia is unknown. Similarly, how ciliary gene mutations result in reduced Gli3 processing that generates a repressor is also not clear. Here we show that Hh signaling inhibits Gli2 and Gli3 phosphorylation by protein kinase A (PKA) in cilia. The cilia related gene Talpid3 (Ta3) mutation results in the reduced processing and phosphorylation of Gli2 and Gli3. Interestingly, Ta3 interacts and colocalizes with PKA regulatory subunit PKARIIß at centrioles in the cell. The centriolar localization and PKA binding regions are located in the N- and C-terminal regions of Ta3, respectively. PKARIIß fails to localize at centrioles in some Ta3 mutant cells. Therefore, our study provides the direct evidence that Gli2 and Gli3 are dephosphorylated and activated in cilia and that impaired Gli2 and Gli3 processing in Ta3 mutant is at least in part due to a decrease in Gli2 and Gli3 phosphorylation.


Assuntos
Proteínas de Ciclo Celular/genética , Cílios/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Organogênese , Transdução de Sinais , Proteínas de Ancoragem à Quinase A/metabolismo , Animais , Anticorpos/metabolismo , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação/genética , Fosfopeptídeos/metabolismo , Fosforilação , Ligação Proteica , Processamento de Proteína Pós-Traducional , Proteína Gli2 com Dedos de Zinco , Proteína Gli3 com Dedos de Zinco
10.
Small ; 14(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29131499

RESUMO

Phase transformation between carbon allotropes usually requires high pressures and high temperatures. Thus, the development of low-temperature phase transition approaches between carbon allotropes is highly desired. Herein, novel amorphous carbon nanocapsules are successfully synthesized by pulsed plasma glow discharge. These nanocapsules are comprised of highly strained carbon clusters encapsulated in a fullerene-like carbon matrix, with the formers serving as nucleation sites. These nucleation sites favored the formation of a diamond unit cell driven by the self-nanoscopic local excessive pressure, thereby significantly decreasing the temperature required for its transformation into a diamond nanocrystal. Under moderate electron beam irradiation (10-20 A cm-2 ) without external heating, self-organization of the energetic carbon clusters into diamond nanocrystals is achieved, whereas the surrounding fullerene-like carbon matrix remains nearly unchanged. Molecular dynamics simulations demonstrate that the defective rings as the active sites dominate the phase transition of amorphous carbon to diamond nanocrystal. The findings may open a promising route to realize phase transformation between carbon allotropes at a lower temperature.

11.
Nanotechnology ; 29(11): 115602, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29313835

RESUMO

We present a direct observation of the transformation of dense amorphous carbon clusters into diamond nanocrystalline under electron beam irradiation by in situ transmission electron microscopy, where the surrounding carbon matrix did not significantly change. Our findings provide clear and convincing evidence for the diamond nanocrystalline evolving from energetic amorphous carbon sites. Furthermore, graphitization of amorphous carbons usually demands a high temperature combined with high pressure. Hence, graphitization of amorphous carbons at relatively low temperatures is highly desired. Here we offer a useful method for catalyst-free graphitization of amorphous carbons by employing moderate electron beam irradiation, without external heating being applied.

12.
Phys Chem Chem Phys ; 20(35): 22445-22454, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29923558

RESUMO

The friction behaviors of highly sp3-hybridized carbon films, including ultra-nanocrystalline diamond and diamond-like carbon materials, strongly depend on the atmosphere. However, the roles of the corresponding molecules in the interfacial bonding characteristics remain a subject of debate. By means of density functional theory calculations, this study aims to fill a knowledge gap about the correlation between the evolving contact quality induced by the adsorption of molecules, and the friction behavior of highly sp3-bonded carbons. The results prove that gas-solid adsorption is responsible for the diversity in friction coefficients of ultra-nanocrystalline diamond and diamond-like carbons in different atmospheres. This study emphasizes the role of terminal states in friction coefficients, and demonstrates that electron lubrication is another available strategy for hydrogenated diamond-like carbons to achieve ultra-low friction. This conclusion is validated by the ultra-low friction coefficient (∼0.009) of hydrogenated diamond-like carbons in a dry nitrogen atmosphere. These findings provide atomic scale descriptions of the surface passivation mechanisms for ultra-nanocrystalline diamond and diamond-like carbons, which contribute to our understanding of their macro-scale friction behaviors.

13.
Dev Biol ; 379(2): 221-8, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23644062

RESUMO

Anterioposterior vertebrate limb patterning is controlled by opposing action between Sonic Hedgehog (Shh) and the Gli3 transcriptional repressor. Unexpectedly, Gli3(Δ699) mutant mice, which are thought to express only a Gli3 repressor and not the full-length activator, exhibit limb phenotypes inconsistent with those of Shh mutant mice. Therefore, it remains debatable whether Shh patterns the anterioposterior limb primarily by inhibiting generation of the Gli3 repressor. However, one caveat is that Gli3(Δ699) may not be as potent as the natural form of Gli3 repressor because of the nature of the mutant allele. In the present study, we created a conditional Gli3 mutant allele that exclusively expresses Gli3 repressor in the presence of Cre recombinase. Using this mutant, we show that the phenotypes of mouse limbs expressing only the Gli3 repressor exhibit no or single digit, resembling those of Shh mutant limbs. Consistent with the limb phenotypes, the expression of genes dependent on Shh signaling is also inhibited in both mutants. This inhibition by the Gli3 repressor is independent of Shh. Thus, our study clarifies the current controversy and provides important genetic evidence to support the hypothesis that Shh patterns the anterioposterior limb primarily through the inhibition of Gli3 repressor formation.


Assuntos
Padronização Corporal/fisiologia , Extremidades/embriologia , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Animais , Sequência de Bases , Primers do DNA/genética , Proteínas Hedgehog/genética , Immunoblotting , Hibridização In Situ , Integrases , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Dados de Sequência Molecular , Mutagênese , Proteínas do Tecido Nervoso/genética , Proteína Gli3 com Dedos de Zinco
14.
J Biol Chem ; 288(41): 29518-29, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23955340

RESUMO

The primary cilium is required for Hedgehog signaling. So far, all known ciliogenic proteins regulate Hedgehog signaling through their role in ciliogenesis. Here we show that the mouse DZIP1 regulates Hedgehog signaling through two mechanisms. First, DZIP1 interacts with GLI3, a transcriptional regulator for Hedgehog signaling, and prevents GLI3 from entering the nucleus. Second, DZIP1 is required for ciliogenesis. We show that DZIP1 colocalizes and interacts with CEP164, a protein localizing at appendages of the mother centrioles, and IFT88, a component of the intraflagellar transport (IFT) machinery. Functionally, both CEP164 and Ninein appendage proteins fail to localize to ciliary appendages in Dzip1 mutant cells; IFT components are not recruited to the basal body of cilia. Importantly, the accumulation of GLI3 in the nucleus is independent of loss of primary cilia in Dzip1 mutant cells. Therefore, DZIP1 is the first known ciliogenic protein that regulates Hedgehog signaling through a dual mechanism and that biochemically links IFT machinery with Hedgehog pathway components.


Assuntos
Cílios/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Linhagem Celular , Células Cultivadas , Centríolos/metabolismo , Centrossomo/metabolismo , Cílios/genética , Cílios/metabolismo , Citoplasma/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Proteínas de Ligação a DNA/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/embriologia , Embrião de Mamíferos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HEK293 , Proteínas Hedgehog/genética , Humanos , Immunoblotting , Fatores de Transcrição Kruppel-Like/genética , Camundongos , Microscopia de Fluorescência , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Interferência de RNA , Transdução de Sinais/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Proteína Gli3 com Dedos de Zinco
15.
Adv Mater ; 36(18): e2309507, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38273713

RESUMO

Maintaining a match between input solar energy and required energy by water supply management is key to achieving efficient interfacial solar-driven evaporation (ISDE). In practice, the solar radiation flux is constantly changing throughout the day, so keeping a dynamic water-energy-balance of ISDE is a big challenge. Herein, a photothermal water diode (WD) evaporator concept is proposed by an integrated hydrophilic/hydrophobic Janus absorber to overcome the issue. Due to the unique unidirectional water transport properties induced by asymmetric wettability, a self-adaptive balance between photothermal energy input and water uptake is established, thus realizing the energy matching and utilization maximization. The experimental and simulation results exhibit that with the increase of sunlight intensity, the water supply speed is significantly accelerated due to the dynamic management and self-regulation on water replenishment. Therefore, an excellent evaporation rate of up to 2.14 kg m-2 h-1 with a high efficiency of 93.7% under 1 sun illumination is achieved. This water diode engineering with Janus wettability provides a novel strategy and extends the path for designing solar evaporation systems with diverse water supply properties, which shows great potential in different environmental conditions.

16.
Development ; 137(12): 2001-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20463034

RESUMO

Gli2 and Gli3 are primary transcriptional regulators that mediate hedgehog (Hh) signaling. Mechanisms that stabilize and destabilize Gli2 and Gli3 are essential for the proteins to promptly respond to Hh signaling or to be inactivated following the activation. In this study, we show that loss of suppressor of fused (Sufu; an inhibitory effector for Gli proteins) results in destabilization of Gli2 and Gli3 full-length activators but not of their C-terminally processed repressors, whereas overexpression of Sufu stabilizes them. By contrast, RNAi knockdown of Spop (a substrate-binding adaptor for the cullin3-based ubiquitin E3 ligase) in Sufu mutant mouse embryonic fibroblasts (MEFs) can restore the levels of Gli2 and Gli3 full-length proteins, but not those of their repressors, whereas introducing Sufu into the MEFs stabilizes Gli2 and Gli3 full-length proteins and rescues Gli3 processing. Consistent with these findings, forced Spop expression promotes Gli2 and Gli3 degradation and Gli3 processing. The functions of Sufu and Spop oppose each other through their competitive binding to the N- and C-terminal regions of Gli3 or the C-terminal region of Gli2. More importantly, the Gli3 repressor expressed by a Gli3 mutant allele (Gli3(Delta699)) can mostly rescue the ventralized neural tube phenotypes of Sufu mutant embryos, indicating that the Gli3 repressor can function independently of Sufu. Our study provides a new insight into the regulation of Gli2 and Gli3 stability and processing by Sufu and Spop, and reveals the unexpected Sufu-independent Gli3 repressor function.


Assuntos
Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Oncogênicas/metabolismo , Transdução de Sinais/fisiologia , Transativadores/metabolismo , Animais , Camundongos , Camundongos Mutantes , Tubo Neural/fisiologia , Proteína GLI1 em Dedos de Zinco , Proteína Gli3 com Dedos de Zinco
17.
Mater Horiz ; 10(10): 4148-4162, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37395527

RESUMO

Two-dimensional (2D) molybdenum disulfide exhibits a variety of intriguing behaviors depending on its orientation layers. Therefore, developing a template-free atomic layer orientation controllable growth approach is of great importance. Here, we demonstrate scalable, template-free, well-ordered vertically-oriented MoS2 nanowire arrays (VO-MoS2 NWAs) embedded in an Ag-MoS2 matrix, directly grown on various substrates (Si, Al, and stainless steel) via one-step sputtering. In the meta-structured film, vertically-standing few-layered MoS2 NWAs of almost micron length (∼720 nm) throughout the entire film bulk. While near the surface, MoS2 lamellae are oriented in parallel, which are beneficial for caging the bonds dangling from the basal planes. Owing to the unique T-type topological characteristics, chemically inert Ag@MoS2 nano-scrolls (NSCs) and nano-crystalline Ag (nc-Ag) nanoparticles (NPs) are in situ formed under the sliding shear force. Thus, incommensurate contact between (002) basal planes and nc-Ag NPs is observed. As a result, robust superlubricity (friction coefficient µ = 0.0039) under humid ambient conditions is reached. This study offers an unprecedented strategy for controlling the basal plane orientation of 2D transition metal dichalcogenides (TMDCs) via substrate independence, using a one-step solution-free easily scalable process without the need for a template, which promotes the potential applications of 2D TMDCs in solid superlubricity.

18.
Adv Mater ; 35(47): e2212100, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37395703

RESUMO

Solar-powered vapor evaporation (SVG), based on the liquid-gas phase conversion concept using solar energy, has been given close attention as a promising technology to address the global water shortage. At molecular level, water molecules escaping from liquid water should overcome the attraction of the molecules on the liquid surface layer to evaporate. For this reason, it is better to reduce the energy required for evaporation by breaking a smaller number of hydrogen bonds or forming weak hydrogen bonds to ensure efficient and convenient vapor production. Many novel evaporator materials and effective water activation strategies have been proposed to stimulate rapid steam production and surpass the theoretical thermal limit. However, an in-depth understanding of the phase/enthalpy change process of water evaporation is unclear. In this review, a summary of theoretical analyses of vaporization enthalpy, general calculations, and characterization methods is provided. Various water activation mechanisms are also outlined to reduce evaporation enthalpy in evaporators. Moreover, unsolved issues associated with water activation are critically discussed to provide a direction for future research. Meanwhile, significant pioneering developments made in SVG are highlighted, hoping to provide a relatively entire chain for more scholars who are just stepping into this field.

19.
Glob Chall ; 7(9): 2300046, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37745828

RESUMO

Taking abundant and sustainable solar energy as the only energy source, solar-powered interface evaporation has been regarded as a promising method to alleviate the pressure of freshwater shortage. However, the uptake of clean water from brine is constantly accompanied by evaporation of water and condensation of vapor, which inevitably generates salt solid, preventing further continuous and stable evaporation. The most direct method is to fabricate a photothermal material with salt self-resistance by using the reflux of salt ions. Here, a superhydrophilic interconnected biomass carbon absorber (SBCA) is prepared by freeze-drying and carbonization, realizing strong liquid pumping, and self-blocking salt. In combination with superior broadband light absorption (94.91%), high porosity (95.9%), superhydrophilicity, and excellent thermal localization, an evaporation device with excellent evaporation rate (2.45 kg m-2 h-1 under 1 kW m-2) is successfully proposed. In the meantime, the porous skeleton and rapid water transport can enhance the diffusion of salt ions and slow down the rate of salt deposition. As a result, no salt deposition is found on the SBCA surface after continuous irradiation at 1 kW m-2 for 15 h. The design can provide a convenient and low-cost efficient strategy for solar steam generators to address clean water acquisition.

20.
Dev Dyn ; 240(4): 766-74, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21337666

RESUMO

The proteolytic processing of Gli2 and Gli3 full-length transcription factors into repressors is a key step of the regulation in Hedgehog (Hh) signaling. The differential Gli2 and Gli3 processing is controlled by the processing determinant domain or PDD, but its significance is not clear. We generated a Gli2 mutant allele, Gli2(3PDD) , in which the Gli3PDD substitutes for the Gli2PDD. As expected, Gli2(3PDD) is processed more efficiently and at a different position as compared to Gli2, indicating that PDD also determines the extent and site of Gli2 and Gli3 processing in vivo. The increase in levels of the Gli2 repressor in Gli2(3PDD) mutant reduces the Hh pathway activity. Gli2(3PDD) processing is still regulated by Hh signaling. These results indicate that the proper balance between the Gli2 full-length activator and repressor is essential for Hh signaling.


Assuntos
Proteínas Hedgehog/fisiologia , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Processamento de Proteína Pós-Traducional/genética , Animais , Células Cultivadas , Regulação para Baixo/genética , Embrião de Mamíferos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/química , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fatores de Transcrição/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima , Proteína Gli2 com Dedos de Zinco
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