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1.
Proc Natl Acad Sci U S A ; 120(18): e2221175120, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37094128

RESUMO

Diffuse midline gliomas (DMGs) including diffuse intrinsic pontine gliomas (DIPGs) bearing lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are lethal childhood brain cancers. These tumors harbor a global reduction in the transcriptional repressive mark H3K27me3 accompanied by an increase in the transcriptional activation mark H3K27ac. We postulated that H3K27M mutations, in addition to altering H3K27 modifications, reprogram the master chromatin remodeling switch/sucrose nonfermentable (SWI/SNF) complex. The SWI/SNF complex can exist in two main forms termed BAF and PBAF that play central roles in neurodevelopment and cancer. Moreover, BAF antagonizes PRC2, the main enzyme catalyzing H3K27me3. We demonstrate that H3K27M gliomas show increased protein levels of the SWI/SNF complex ATPase subunits SMARCA4 and SMARCA2, and the PBAF component PBRM1. Additionally, knockdown of mutant H3K27M lowered SMARCA4 protein levels. The proteolysis targeting chimera (PROTAC) AU-15330 that simultaneously targets SMARCA4, SMARCA2, and PBRM1 for degradation exhibits cytotoxicity in H3.3K27M but not H3 wild-type cells. AU-15330 lowered chromatin accessibility measured by ATAC-Seq at nonpromoter regions and reduced global H3K27ac levels. Integrated analysis of gene expression, proteomics, and chromatin accessibility in AU-15330-treated cells demonstrated reduction in the levels of FOXO1, a key member of the forkhead family of transcription factors. Moreover, genetic or pharmacologic targeting of FOXO1 resulted in cell death in H3K27M cells. Overall, our results suggest that H3K27M up-regulates SMARCA4 levels and combined targeting of SWI/SNF ATPases in H3.3K27M can serve as a potent therapeutic strategy for these deadly childhood brain tumors.


Assuntos
Neoplasias Encefálicas , Glioma Pontino Intrínseco Difuso , Glioma , Humanos , Criança , Histonas/genética , Adenosina Trifosfatases/metabolismo , Lisina/genética , Cromatina , Glioma/genética , Neoplasias Encefálicas/genética , Mutação , DNA Helicases/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo
2.
Mol Biol Evol ; 41(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38768215

RESUMO

High mountains harbor a considerable proportion of biodiversity, but we know little about how diverse plants adapt to the harsh environment. Here we finished a high-quality genome assembly for Dasiphora fruticosa, an ecologically important plant distributed in the Qinghai-Tibetan Plateau and lowland of the Northern Hemisphere, and resequenced 592 natural individuals to address how this horticulture plant adapts to highland. Demographic analysis revealed D. fruticosa underwent a bottleneck after Naynayxungla Glaciation. Selective sweep analysis of two pairs of lowland and highland populations identified 63 shared genes related to cell wall organization or biogenesis, cellular component organization, and dwarfism, suggesting parallel adaptation to highland habitats. Most importantly, we found that stronger purging of estimated genetic load due to inbreeding in highland populations apparently contributed to their adaptation to the highest mountain. Our results revealed how plants could tolerate the extreme plateau, which could provide potential insights for species conservation and crop breeding.


Assuntos
Genoma de Planta , Seleção Genética , Adaptação Fisiológica/genética , Altitude
3.
Small ; 20(22): e2309900, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38312091

RESUMO

All-hydrogel supercapacitors are emerging as promising power sources for next-generation wearable electronics due to their intrinsic mechanical flexibility, eco-friendliness, and enhanced safety. However, the insufficient interfacial adhesion between the electrode and electrolyte and the frozen hydrogel matrices at subzero temperatures largely limit the practical applications of all-hydrogel supercapacitors. Here, an all-hydrogel supercapacitor is reported with robust interfacial contact and anti-freezing property, fabricated by in situ polymerizing hydrogel electrolyte onto hydrogel electrodes. The robust interfacial adhesion is developed by the synergistic effect of a tough hydrogel matrix and topological entanglements. Meanwhile, the incorporation of zinc chloride (ZnCl2) in the hydrogel electrolyte prevents the freezing of water solvents and endows the all-hydrogel supercapacitor with mechanical flexibility and fatigue resistance across a wide temperature range of 20 °C to -60 °C. Such all-hydrogel supercapacitor demonstrates satisfactory low-temperature electrochemical performance, delivering a high energy density of 11 mWh cm-2 and excellent cycling stability with a capacitance retention of 90% over 10000 cycles at -40 °C. Notably, the fabricated all-hydrogel supercapacitor can endure dynamic deformations and operate well under 2000 tension cycles even at -40 °C, without experiencing delamination and electrochemical failure. This work offers a promising strategy for flexible energy storage devices with low-temperature adaptability.

4.
Proc Biol Sci ; 290(2003): 20230659, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37491959

RESUMO

Demonstrating the process of transregional biogeography and mechanisms underlying evolutionary radiations is crucial to understanding biological evolution. Here, we use Hydrangeeae (Hydrangeaceae), a tribe with a unique disjunct distribution and complex trait variations, using a solid phylogenetic framework, to investigate how geographical and climatic factors interact with functional traits to trigger plant evolutionary radiations. We constructed the first highly supported and dated phylogenetic framework using 79 protein-coding genes obtained from 81 plastomes, representing 63 species and all major clades, and found that most extant species originated from asynchronous diversification of two lineages undergoing repeated expansion and retraction, at middle and high latitudes of the Northern Hemisphere between East Asia and North America, during the Eocene to Pleistocene (driven by geologic and climatic dynamics). In accordance with these drivers, interactions of flora between central-eastern China and Japan occurred frequently after the Late Tertiary. We found that resource limitation and range fragmentation probably accelerated the diversification of Hydrangeeae, which supports the resource-use hypothesis. Our study sheds light on the evolutionary radiation and assembly of flora within East Asia, and the East Asian-North American disjunction, through integration of phylogenomic and biogeographic data with functional trait and ecological data.


Assuntos
Hydrangeaceae , Filogenia , Evolução Biológica , Ásia Oriental , América do Norte , Filogeografia
5.
J Integr Plant Biol ; 65(12): 2619-2630, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837251

RESUMO

Reconstructing a robust species phylogeny and disentangling the evolutionary and biogeographic history of the gymnosperm genus Ephedra, which has a large genome and rich polyploids, remain a big challenge. Here we reconstructed a transcriptome-based phylogeny of 19 diploid Ephedra species, and explored evolutionary reticulations in this genus represented by 50 diploid and polyploid species, using four low-copy nuclear and nine plastid genes. The diploid species phylogeny indicates that the Mediterranean species diverged first, and the remaining species split into three clades, including the American species (Clade A), E. rhytidosperma, and all other Asian species (Clade B). The single-gene trees placed E. rhytidosperma sister to Clade A, Clade B, or Clades A + B in similar proportions, suggesting that radiation and gene flow likely occurred in the early evolution of Ephedra. In addition, reticulate evolution occurred not only among the deep nodes, but also in the recently evolved South American species, which further caused difficulty in phylogenetic reconstruction. Moreover, we found that allopolyploid speciation was pervasive in Ephedra. Our study also suggests that Ephedra very likely originated in the Tethys coast during the late Cretaceous, and the South American Ephedra species have a single origin by dispersal from Mexico or North America.


Assuntos
Ephedra , Filogenia , Ephedra/genética , Diploide , Plastídeos
6.
Fish Shellfish Immunol ; 97: 421-431, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31846777

RESUMO

During the immune defense reaction of invertebrate, a plenty of reactive oxygen species (ROS) could be induced to product. Though ROS can kill foreign invaders, the accumulation of these reactive molecules in animals will cause serious cell damage. Carotenoids could function as scavengers of oxygen radicals. In this research, cDNA and genomic DNA of one carotenoid isomerooxygenase gene (named EcNinaB-X1) were cloned from Exopalaemon carinicauda. EcNinaB-X1 gene was composed of 12 exons and 11 introns. EcNinaB-X1 knock-out (KO) prawns were produced via CRISPR/Cas9 technology and the change of their phenotypes were analyzed. Of the 400 injected one-cell stage embryos with cas9 mRNA and one sgRNA targeting the first exon of EcNinaB-X1 gene, 26 EcNinaB-X1-KO prawns were generated and the mutant rate reached 6.5% after embryo injection. The EcNinaB-X1-KO prawns had significant lower mortality than those in wild-type group when the prawns were challenged with Vibrio parahaemolyticus or Aeromonas hydrophila. In conclusion, we first demonstrate the function of the carotenoid isomerooxygenase gene in immune defense of E. carinicauda by performing directed, heritable gene mutagenesis.


Assuntos
Proteínas de Artrópodes/genética , Sistemas CRISPR-Cas , Técnicas de Inativação de Genes/métodos , Oxigenases/genética , Palaemonidae/enzimologia , Palaemonidae/genética , Aeromonas hydrophila/patogenicidade , Animais , Carotenoides/química , Deleção de Genes , Imunidade Inata , Mutagênese , Palaemonidae/microbiologia , Vibrio parahaemolyticus/patogenicidade
7.
Phys Chem Chem Phys ; 21(21): 11226-11233, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31099369

RESUMO

Magnesium borohydride (Mg(BH4)2) has been considered as a potential material for hydrogen storage. In this paper, density functional theory studies have been carried out on native point defects and electrically active impurities (Ni and Ti) in Mg(BH4)2. A detailed analysis of the geometrical structures, energetics and migration of the defects reveals that hydrogen related defects are charged and their formation energies are Fermi-level dependent. We propose a specific mechanism for the decomposition of Mg(BH4)2: the self-diffusion of Mgi2+ is the rate-limiting process for decomposing Mg(BH4)2. Moreover, Ni and Ti impurities can tailor the hydrogen desorption kinetics of Mg(BH4)2 by shifting the Fermi level, but the effects of impurities on shifting the Fermi levels are related to how the impurity is incorporated into Mg(BH4)2.

8.
Mol Phylogenet Evol ; 107: 345-355, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27908741

RESUMO

Phylogenomics has shown great potential in resolving evolutionary relationships at different taxonomical levels. However, it remains controversial whether all orthologous genes under different selective pressures can be concatenated for phylogenomic reconstruction. Here we used sect. Cyathophora of Pedicularis, one of the most species-rich genera of angiosperms in the alpine and arctic regions of the Northern Hemisphere, as a model to investigate the efficiency of RNA-seq in resolving relationships of closely related congeneric species. Flower transcriptomes were sequenced for all species of sect. Cyathophora and two outgroup species. Forty-one highly conserved single-/low-copy nuclear genes and 1553 orthologous groups (OGs) were identified and concatenated into five datasets based on gene copy numbers and Ka/Ks values to reconstruct the phylogeny of section Cyathophora. We also tested how many genes minimally can resolve the interspecific relationships, and reconstructed the evolutionary history of some floral characters in sect. Cyathophora. The results showed that the five different datasets consistently resolved the interspecific relationships of sect. Cyathophora, and the interspecific relationships can be robustly reconstructed with maximal support when ⩾20 single-/low-copy nuclear genes or 25 OGs are used. Our study suggests that all OGs under different selective pressures can be concatenated for phylogenomic reconstruction, and provides a successful and efficient use of RNA-seq in reconstructing interspecific relationships of a non-model plant group with recent radiations.


Assuntos
Pedicularis/classificação , Pedicularis/genética , Filogenia , Análise de Sequência de RNA/métodos , Regiões Árticas , Sequência de Bases , Núcleo Celular/genética , Bases de Dados Genéticas , Flores/genética , Dosagem de Genes , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genômica , Funções Verossimilhança , RNA de Plantas/genética , Especificidade da Espécie , Fatores de Tempo , Transcriptoma/genética
9.
Acta Neuropathol ; 134(5): 705-714, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28733933

RESUMO

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.


Assuntos
Ependimoma/metabolismo , Neoplasias Infratentoriais/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Criança , Pré-Escolar , Intervalo Livre de Doença , Ependimoma/mortalidade , Ependimoma/patologia , Feminino , Humanos , Lactente , Neoplasias Infratentoriais/mortalidade , Neoplasias Infratentoriais/patologia , Masculino , Prognóstico , Sistema de Registros , Taxa de Sobrevida
10.
Mar Drugs ; 14(8)2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27517939

RESUMO

Anti-lipopolysaccharide factors (ALFs) with a LPS-binding domain (LBD) are considered to have broad spectrum antimicrobial activities and certain antiviral properties in crustaceans. FcALF2 was one isoform of ALFs isolated from the Chinese shrimp Fenneropenaeus chinensis. Our previous study showed that a modified LBD domain (named LBDv) of FcALF2 exhibited a highly enhanced antimicrobial activity. In the present study, a modified FcALF2 gene (mFcALF2), in which the LBD was substituted by LBDv, was designed and synthesized. This gene was successfully expressed in yeast Pichia pastoris GS115 eukaryotic expression system, and the characteristics of the recombinant protein mFcALF2 were analyzed. mFcALF2 exhibited apparent antibacterial activities against Gram-negative bacteria, including Escherichia coli, Vibrio alginolyticus, Vibrio harveyi, and Vibrio parahaemolyticus, and Gram-positive bacteria, including Bacillus licheniformis and Staphylococcus epidermidis. In addition, mFcALF2 could reduce the propagation of white spot syndrome virus (WSSV) in vivo by pre-incubation with virus. The present study paves the way for developing antimicrobial drugs in aquaculture.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Antivirais/farmacologia , Proteínas de Artrópodes/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Vírus da Síndrome da Mancha Branca 1/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/biossíntese , Peptídeos Catiônicos Antimicrobianos/genética , Aquicultura , Proteínas de Artrópodes/biossíntese , Proteínas de Artrópodes/genética , Lipopolissacarídeos/metabolismo , Testes de Sensibilidade Microbiana , Penaeidae/genética , Pichia , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Isoformas de Proteínas/farmacologia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia
11.
J Integr Plant Biol ; 58(2): 178-87, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26172034

RESUMO

Floral nectar is thought to be one of the most important rewards that attract pollinators in Pedicularis; however, few studies have examined variation of nectary structure and/or nectar secretion in the genus, particularly among closely related species. Here we investigated nectary morphology, nectar quality, and nectar production dynamics in flowers of Pedicularis section Cyathophora. We found a conical floral nectary at the base of the ovary in species of the rex-thamnophila clade. Stomata were found on the surface of the nectary, and copious starch grains were detected in the nectary tissues. In contrast, a semi-annular nectary was found in flowers of the species of the superba clade. Only a few starch grains were observed in tissues of the semi-annular nectary, and the nectar sugar concentration in these flowers was much lower than that in the flowers of the rex-thamnophila clade. Our results indicate that the floral nectary has experienced considerable morphological, structural, and functional differentiation among closely related species of Pedicularis. This could have affected nectar production, leading to a shift of the pollination mode. Our results also imply that variation of the nectary morphology and nectar production may have played an important role in the speciation of sect. Cyathophora.


Assuntos
Flores/fisiologia , Pedicularis/fisiologia , Néctar de Plantas/biossíntese , Animais , Abelhas/fisiologia , Carboidratos/análise , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Flores/ultraestrutura , Pedicularis/anatomia & histologia , Pedicularis/crescimento & desenvolvimento , Pedicularis/ultraestrutura , Polinização , Isolamento Reprodutivo , Especificidade da Espécie
12.
J Neurosci ; 34(21): 7124-36, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24849348

RESUMO

Hyperphosphorylation and accumulation of tau aggregates are prominent features in tauopathies, including Alzheimer's disease, but the impact of loss of tau function on synaptic and cognitive deficits remains poorly understood. We report that old (19-20 months; OKO) but not middle-aged (8-9 months; MKO) tau knock-out mice develop Morris Water Maze (MWM) deficits and loss of hippocampal acetylated α-tubulin and excitatory synaptic proteins. Mild motor deficits and reduction in tyrosine hydroxylase (TH) in the substantia nigra were present by middle age, but did not affect MWM performance, whereas OKO mice showed MWM deficits paralleling hippocampal deficits. Deletion of tau, a microtubule-associated protein (MAP), resulted in increased levels of MAP1A, MAP1B, and MAP2 in MKO, followed by loss of MAP2 and MAP1B in OKO. Hippocampal synaptic deficits in OKO mice were partially corrected with dietary supplementation with docosahexaenoic acid (DHA) and both MWM and synaptic deficits were fully corrected by combining DHA with α-lipoic acid (ALA), which also prevented TH loss. DHA or DHA/ALA restored phosphorylated and total GSK3ß and attenuated hyperactivation of the tau C-Jun N-terminal kinases (JNKs) while increasing MAP1B, dephosphorylated (active) MAP2, and acetylated α-tubulin, suggesting improved microtubule stability and maintenance of active compensatory MAPs. Our results implicate the loss of MAP function in age-associated hippocampal deficits and identify a safe dietary intervention, rescuing both MAP function and TH in OKO mice. Therefore, in addition to microtubule-stabilizing therapeutic drugs, preserving or restoring compensatory MAP function may be a useful new prevention strategy.


Assuntos
Envelhecimento/patologia , Hipocampo/patologia , Aprendizagem em Labirinto/fisiologia , Sinapses/metabolismo , Proteínas tau/deficiência , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Animais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Hipocampo/efeitos dos fármacos , Deficiências da Aprendizagem/dietoterapia , Deficiências da Aprendizagem/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transtornos dos Movimentos/dietoterapia , Transtornos dos Movimentos/etiologia , Desempenho Psicomotor/fisiologia , Tempo de Reação/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Sinapses/efeitos dos fármacos , Sinapses/genética , Ácido Tióctico/administração & dosagem
13.
Neurobiol Dis ; 82: 552-560, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26369878

RESUMO

Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on ß-amyloid (Aß) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Aß oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Aß indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Aß plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Aß oligomer levels in the hippocampus. Further quantification of specific conformational populations of Aß oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Aß oligomers and decreased prefibrillar (i.e. putatively more toxic) Aß oligomers. These results provide in vivo evidence suggesting that DHA can modulate Aß aggregation by stabilizing soluble fibrillar Aß oligomers and thus reduce the formation of both Aß plaques and prefibrillar Aß oligomers. However, since fibrillar Aß oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Aß oligomer levels for more effective prevention of AD in clinical settings.


Assuntos
Doença de Alzheimer/dietoterapia , Peptídeos beta-Amiloides/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Hipocampo/metabolismo , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/dietoterapia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hipocampo/patologia , Humanos , Masculino , Aprendizagem em Labirinto , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Placa Amiloide/psicologia , Presenilina-1/genética , Presenilina-1/metabolismo , Multimerização Proteica , Ratos Sprague-Dawley , Ratos Transgênicos , Resultado do Tratamento
14.
Fish Shellfish Immunol ; 47(2): 824-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26492995

RESUMO

Vascular endothelial growth factors (VEGFs) are important signaling proteins in VEGF signaling pathway which play key roles in inducing endothelial cell proliferation, migration, angiogenesis, vascular permeability, inhibition of apoptosis and virus infection. In the present study, we isolated and characterized two VEGF genes, LvVEGF1 and LvVEGF2 from Litopenaeus vannamei. The deduced amino acid sequences of both LvVEGF1 and LvVEGF2 contained a signal peptide, a typical PDGF/VEGF domain and a cysteine knot motif (CXCXC). Tissue distribution analysis showed that LvVEGF1 was predominantly expressed in lymphoid organ (Oka) while LvVEGF2 was mainly detected in gill and hemocytes. The transcriptional levels of LvVEGF1 in Oka and LvVEGF2 in gill or hemocytes were apparently up-regulated during WSSV infection. Double-stranded RNA interference was used for further functional studies. The data showed that silencing of LvVEGF1 and LvVEGF2 caused a decrease of the copy numbers of the virus in WSSV infected shrimp and a reduction of the cumulative mortality rate of shrimp during WSSV infection. The present study indicated that LvVEGF1 and LvVEGF2 might facilitate WSSV infection, which provided new evidence to understand the function of VEGF signaling pathway during WSSV infection in shrimp.


Assuntos
Proteínas de Artrópodes/genética , Regulação da Expressão Gênica , Penaeidae/genética , Fatores de Crescimento do Endotélio Vascular/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos , Penaeidae/crescimento & desenvolvimento , Penaeidae/metabolismo , Penaeidae/virologia , Filogenia , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/metabolismo , Alinhamento de Sequência , Fatores de Crescimento do Endotélio Vascular/química , Fatores de Crescimento do Endotélio Vascular/metabolismo
15.
J Biol Chem ; 288(6): 4056-65, 2013 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-23264626

RESUMO

The mechanisms underlying Tau-related synaptic and cognitive deficits and the interrelationships between Tau species, their clearance pathways, and synaptic impairments remain poorly understood. To gain insight into these mechanisms, we examined these interrelationships in aged non-mutant genomic human Tau mice, with established Tau pathology and neuron loss. We also examined how these interrelationships changed with an intervention by feeding mice either a control diet or one containing the brain permeable beta-amyloid and Tau aggregate binding molecule curcumin. Transgene-dependent elevations in soluble and insoluble phospho-Tau monomer and soluble Tau dimers accompanied deficits in behavior, hippocampal excitatory synaptic markers, and molecular chaperones (heat shock proteins (HSPs)) involved in Tau degradation and microtubule stability. In human Tau mice but not control mice, HSP70, HSP70/HSP72, and HSP90 were reduced in membrane-enriched fractions but not in cytosolic fractions. The synaptic proteins PSD95 and NR2B were reduced in dendritic fields and redistributed into perikarya, corresponding to changes observed by immunoblot. Curcumin selectively suppressed levels of soluble Tau dimers, but not of insoluble and monomeric phospho-Tau, while correcting behavioral, synaptic, and HSP deficits. Treatment increased PSD95 co-immunoprecipitating with NR2B and, independent of transgene, increased HSPs implicated in Tau clearance. It elevated HSP90 and HSC70 without increasing HSP mRNAs; that is, without induction of the heat shock response. Instead curcumin differentially impacted HSP90 client kinases, reducing Fyn without reducing Akt. In summary, curcumin reduced soluble Tau and elevated HSPs involved in Tau clearance, showing that even after tangles have formed, Tau-dependent behavioral and synaptic deficits can be corrected.


Assuntos
Anti-Inflamatórios não Esteroides/farmacocinética , Comportamento Animal/efeitos dos fármacos , Curcumina/farmacologia , Proteínas de Choque Térmico/metabolismo , Multimerização Proteica/efeitos dos fármacos , Sinapses/metabolismo , Tauopatias/metabolismo , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Animais , Proteína 4 Homóloga a Disks-Large , Feminino , Proteínas de Choque Térmico/genética , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Multimerização Proteica/genética , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-fyn/genética , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Solubilidade/efeitos dos fármacos , Sinapses/genética , Sinapses/patologia , Tauopatias/tratamento farmacológico , Tauopatias/genética , Tauopatias/patologia , Proteínas tau/genética
16.
Brain ; 135(Pt 12): 3735-48, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23183235

RESUMO

Alzheimer's disease is a devastating cureless neurodegenerative disorder affecting >35 million people worldwide. The disease is caused by toxic oligomers and aggregates of amyloid ß protein and the microtubule-associated protein tau. Recently, the Lys-specific molecular tweezer CLR01 has been shown to inhibit aggregation and toxicity of multiple amyloidogenic proteins, including amyloid ß protein and tau, by disrupting key interactions involved in the assembly process. Following up on these encouraging findings, here, we asked whether CLR01 could protect primary neurons from Alzheimer's disease-associated synaptotoxicity and reduce Alzheimer's disease-like pathology in vivo. Using cell culture and brain slices, we found that CLR01 effectively inhibited synaptotoxicity induced by the 42-residue isoform of amyloid ß protein, including ∼80% inhibition of changes in dendritic spines density and long-term potentiation and complete inhibition of changes in basal synaptic activity. Using a radiolabelled version of the compound, we found that CLR01 crossed the mouse blood-brain barrier at ∼2% of blood levels. Treatment of 15-month-old triple-transgenic mice for 1 month with CLR01 resulted in a decrease in brain amyloid ß protein aggregates, hyperphosphorylated tau and microglia load as observed by immunohistochemistry. Importantly, no signs of toxicity were observed in the treated mice, and CLR01 treatment did not affect the amyloidogenic processing of amyloid ß protein precursor. Examining induction or inhibition of the cytochrome P450 metabolism system by CLR01 revealed minimal interaction. Together, these data suggest that CLR01 is safe for use at concentrations well above those showing efficacy in mice. The efficacy and toxicity results support a process-specific mechanism of action of molecular tweezers and suggest that these are promising compounds for developing disease-modifying therapy for Alzheimer's disease and related disorders.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/química , Encéfalo/patologia , Lisina/química , Neurônios/fisiologia , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/farmacologia , Precursor de Proteína beta-Amiloide/genética , Animais , Antiparasitários/química , Antiparasitários/uso terapêutico , Barreira Hematotesticular/efeitos dos fármacos , Barreira Hematotesticular/fisiologia , Células Cultivadas , Sistema Enzimático do Citocromo P-450/metabolismo , Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/patologia , Modelos Animais de Doenças , Estimulação Elétrica , Comportamento Exploratório/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/genética , Lisina/farmacologia , Camundongos , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Isoformas de Proteínas/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/genética , Proteínas tau/genética
17.
Comput Biol Med ; 153: 106518, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36641934

RESUMO

Alzheimer's disease (AD) is a common cognitive disorder. Recently, many computer-aided diagnostic techniques have been used for AD prediction utilizing deep learning technology, among which graph neural networks have received increasing attention owing to their ability to model sample relationships on large population graphs. Most of the existing graph-based methods predict diseases according to a single model, which makes it difficult to select an appropriate node embedding algorithm for a certain classification task. Moreover, integrating data from different patterns into a unified model to improve the quality of disease diagnosis remains a challenge. Hence, in this study, we aimed to develop a multi-model fusion framework for AD prediction. A spectral graph attention model was used to aggregate intra- and inter-cluster node embeddings of normal and diseased populations, whereafter, a bilinear aggregation model was applied as an auxiliary model to enhance the abnormality degree in different categories of populations, and finally, an adaptive fusion module was designed to dynamically fuse the results of both models and enhance AD prediction. Compared to other comparison methods, the model proposed in this study provides the best results.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico , Algoritmos , Redes Neurais de Computação
18.
Materials (Basel) ; 16(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37241361

RESUMO

The continuous decline of traditional fossil energy has cast the shadow of an energy crisis on human society. Hydrogen generated from renewable energy sources is considered as a promising energy carrier, which can effectively promote the energy transformation of traditional high-carbon fossil energy to low-carbon clean energy. Hydrogen storage technology plays a key role in realizing the application of hydrogen energy and liquid organic hydrogen carrier technology, with many advantages such as storing hydrogen efficiently and reversibly. High-performance and low-cost catalysts are the key to the large-scale application of liquid organic hydrogen carrier technology. In the past few decades, the catalyst field of organic liquid hydrogen carriers has continued to develop and has achieved some breakthroughs. In this review, we summarized recent significant progress in this field and discussed the optimization strategies of catalyst performance, including the properties of support and active metals, metal-support interaction and the combination and proportion of multi-metals. Moreover, the catalytic mechanism and future development direction were also discussed.

19.
Nanomicro Lett ; 16(1): 22, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982913

RESUMO

Solid-state zinc-ion capacitors are emerging as promising candidates for large-scale energy storage owing to improved safety, mechanical and thermal stability and easy-to-direct stacking. Hydrogel electrolytes are appealing solid-state electrolytes because of eco-friendliness, high conductivity and intrinsic flexibility. However, the electrolyte/electrode interfacial contact and anti-freezing properties of current hydrogel electrolytes are still challenging for practical applications of zinc-ion capacitors. Here, we report a class of hydrogel electrolytes that couple high interfacial adhesion and anti-freezing performance. The synergy of tough hydrogel matrix and chemical anchorage enables a well-adhered interface between hydrogel electrolyte and electrode. Meanwhile, the cooperative solvation of ZnCl2 and LiCl hybrid salts renders the hydrogel electrolyte high ionic conductivity and mechanical elasticity simultaneously at low temperatures. More significantly, the Zn||carbon nanotubes hybrid capacitor based on this hydrogel electrolyte exhibits low-temperature capacitive performance, delivering high-energy density of 39 Wh kg-1 at -60 °C with capacity retention of 98.7% over 10,000 cycles. With the benefits of the well-adhered electrolyte/electrode interface and the anti-freezing hydrogel electrolyte, the Zn/Li hybrid capacitor is able to accommodate dynamic deformations and function well under 1000 tension cycles even at -60 °C. This work provides a powerful strategy for enabling stable operation of low-temperature zinc-ion capacitors.

20.
Hortic Res ; 10(1): uhac241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643737

RESUMO

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

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