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1.
Proc Natl Acad Sci U S A ; 120(40): e2302361120, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37738291

RESUMO

The almost simultaneous emergence of major animal phyla during the early Cambrian shaped modern animal biodiversity. Reconstructing evolutionary relationships among such closely spaced branches in the animal tree of life has proven to be a major challenge, hindering understanding of early animal evolution and the fossil record. This is particularly true in the species-rich and highly varied Mollusca where dramatic inconsistency among paleontological, morphological, and molecular evidence has led to a long-standing debate about the group's phylogeny and the nature of dozens of enigmatic fossil taxa. A critical step needed to overcome this issue is to supplement available genomic data, which is plentiful for well-studied lineages, with genomes from rare but key lineages, such as Scaphopoda. Here, by presenting chromosome-level genomes from both extant scaphopod orders and leveraging complete genomes spanning Mollusca, we provide strong support for Scaphopoda as the sister taxon of Bivalvia, revitalizing the morphology-based Diasoma hypothesis originally proposed 50 years ago. Our molecular clock analysis confidently dates the split between Bivalvia and Scaphopoda at ~520 Ma, prompting a reinterpretation of controversial laterally compressed Early Cambrian fossils, including Anabarella, Watsonella, and Mellopegma, as stem diasomes. Moreover, we show that incongruence in the phylogenetic placement of Scaphopoda in previous phylogenomic studies was due to ancient incomplete lineage sorting (ILS) that occurred during the rapid radiation of Conchifera. Our findings highlight the need to consider ILS as a potential source of error in deep phylogeny reconstruction, especially in the context of the unique nature of the Cambrian Explosion.


Assuntos
Bivalves , Animais , Filogenia , Biodiversidade , Movimento Celular , Suplementos Nutricionais
2.
Macromol Rapid Commun ; 45(6): e2300613, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38157222

RESUMO

Hydrogels are ideal materials for flexible electronic devices based on their smooth ion channels and considerable mechanical flexibility. A substantial volume of aqueous solution is required to enable the smooth flow of ions, resulting in the agony of low-temperature freezing; besides, long-term exposure to bending/tensile tress triggers fatigue issues. Therefore, it is a great challenge to prepare hydrogels with both freeze-resistance and long-term durability. Herein, a polyacrylic acid-based hydrogel with both hydrophobic interaction and dynamic reversible covalent bonding cross-linking networks is preparing (DC-hydrogel) by polymerizing a bi-functional imidazole-type ionic liquid monomer with integrated disulfide and alkene bonds (DS/DB-IL) and an octadecyl methacrylate, achieving self-healing. The DS/DB-IL anchored into the polymer backbone has a high affinity with water, reducing the freezing point of water, while the DS/DB-IL with free ions provides superior ionic conductivity to the DC-hydrogel. The polyacrylic acid with abundant carboxyl gives hydrogel good self-adhesiveness to different substrates. Ionotronics with resistance-type sensors with stable output performance are fabricated and explored its application to joint motion and health information. Moreover, hydrogel-based sensing arrays with high resolution and accuracy are fabricated to identify 2D distribution of stress. The hydrogels have great promise for various ionotronics in many fields.


Assuntos
Alcenos , Hidrogéis , Dissulfetos , Condutividade Elétrica , Água
3.
Fish Shellfish Immunol ; 141: 109084, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37722439

RESUMO

Air exposure (AE) is a significant environmental stressor that can lead to desiccation, hypoxia, starvation, and disruption of cellular homeostasis in marine bivalves. Autophagy is a highly conserved catabolic pathway that facilitates the degradation of damaged macromolecules and organelles, thereby supporting cellular stress responses. To date, autophagy-mediated resistance mechanisms to AE stress remain largely elusive in bivalves. In this study, we performed a multi-tool approach to investigate the autophagy-related physiological regulation in hard clams (Mercenaria mercenaria) under different duration of AE (T = 0, 1, 5, 10, 20, 30 days). We observed that autophagy of haemocytes was significantly activated on day 5. However, autophagy activity began to significantly decline from day 10 to day 30. Autophagy was significantly inhibited after antioxidant treatment, indicating that reactive oxygen species (ROS) was an endogenous inducer of autophagy. A significant decline in the survival rate of hard clams was observed after injection of ammonium chloride or carbamazepine during AE stress, suggesting that moderate autophagy was conducive for clam survival under AE stress. We also observed DNA breaks and high levels of apoptosis in haemocytes on day 10. Activation of apoptosis lagged behind autophagy, and the relationship between autophagy and apoptosis might shift from antagonism to synergy with the duration of stress. This study provides novel insights into the stress resistance mechanisms in marine bivalves.


Assuntos
Mercenaria , Animais , Mercenaria/genética , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo/fisiologia , Antioxidantes/metabolismo , Homeostase , Autofagia
4.
BMC Biol ; 19(1): 15, 2021 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-33487168

RESUMO

BACKGROUND: Inhibitors of apoptosis (IAPs) are critical regulators of programmed cell death that are essential for development, oncogenesis, and immune and stress responses. However, available knowledge regarding IAP is largely biased toward humans and model species, while the distribution, function, and evolutionary novelties of this gene family remain poorly understood in many taxa, including Mollusca, the second most speciose phylum of Metazoa. RESULTS: Here, we present a chromosome-level genome assembly of an economically significant bivalve, the hard clam Mercenaria mercenaria, which reveals an unexpected and dramatic expansion of the IAP gene family to 159 members, the largest IAP gene repertoire observed in any metazoan. Comparative genome analysis reveals that this massive expansion is characteristic of bivalves more generally. Reconstruction of the evolutionary history of molluscan IAP genes indicates that most originated in early metazoans and greatly expanded in Bivalvia through both lineage-specific tandem duplication and retroposition, with 37.1% of hard clam IAPs located on a single chromosome. The expanded IAPs have been subjected to frequent domain shuffling, which has in turn shaped their architectural diversity. Further, we observed that extant IAPs exhibit dynamic and orchestrated expression patterns among tissues and in response to different environmental stressors. CONCLUSIONS: Our results suggest that sophisticated regulation of apoptosis enabled by the massive expansion and diversification of IAPs has been crucial for the evolutionary success of hard clam and other molluscan lineages, allowing them to cope with local environmental stresses. This study broadens our understanding of IAP proteins and expression diversity and provides novel resources for studying molluscan biology and IAP function and evolution.


Assuntos
Apoptose/genética , Genoma , Proteínas Inibidoras de Apoptose/genética , Mercenaria/fisiologia , Animais , Proteínas Inibidoras de Apoptose/metabolismo
5.
Genomics ; 113(4): 2847-2859, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34153497

RESUMO

Intertidal bivalves are constantly exposed to air due to daily and seasonal tidal cycles. The hard clam Mercenaria mercenaria is an economically important bivalve species and often subjected to air exposure for more than 10 days during long-distance transportation. Hard clam exhibits remarkable tolerance to air exposure. In this study, we performed RNA sequencing on hemocytes of M. mercenaria exposed to air for 0, 1, 5, 10, 20 and 30 days. The overall and dynamic molecular responses of hard clams to air exposure were revealed by different transcriptomic analysis strategies. As a result, most cytochrome P450 1A and 3A, and monocarboxylate transporter family members were up-regulated during air exposure. Additionally, the dominant molecular process in response to 5-d, 10-d, 20-d and 30-d air exposure was refolding of misfolded proteins in endoplasmic reticulum, lysosome-mediated degradation of phospholipids, protein metabolism and reorganization of cytoskeleton, and activation of anti-apoptotic process, respectively. Our results facilitated comprehensive understanding of the tolerance mechanisms of intertidal bivalves to air exposure.


Assuntos
Mercenaria , Animais , Perfilação da Expressão Gênica , Hemócitos , Mercenaria/genética , RNA-Seq , Análise de Sequência de RNA
6.
Medicina (Kaunas) ; 58(3)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35334532

RESUMO

Transcatheter aortic valve implantation (TAVI) has evolved to be the treatment of choice for patients with severe aortic stenosis and high perioperative risk. Cardiogenic shock is one of the most severe complications during the TAVI procedure, especially as the prognosis of cardiogenic shock secondary to aortic stenosis is very poor. This situation can be challenging, while extracorporeal membranous oxygenation (ECMO) can be a treatment option. Here, we reported on an 88-year-old female patient who had been diagnosed as non-ST-elevation myocardial infarction (NSTEMI) and critical aortic valve stenosis (AS) with a logistic Euroscore of 25%. Percutaneous coronary angioplasty (PCI) was performed smoothly and developed tachy-brady arrhythmia of atrial fibrillation then cardiac arrest at the beginning of the TAVI procedure. A v-a ECMO was installed at her left femoral side. Afterward, the TAVI procedure was completed accordingly; her consciousness recovered and Levosimendan therapy enhanced her left-ventricular ejection fraction (LVEF) from 22% to 40%. Five days after TAVI, ECMO was replaced by intra-aortic balloon pumping (IABP) and it was removed 3 days later. A minor complication of this therapy, e.g., muscular weakness in her left leg, was noted. The patient underwent rehabilitation for about 2 months, and was discharged from hospital with a wheel chair and clear consciousness. At the 24 month follow-up she was in good recovery and was able to walk upstairs to the second floor again. Our experience suggests that one indication of prophylactic use of ECMO is for patients with an unstable hemodynamic condition.


Assuntos
Estenose da Valva Aórtica , Oxigenação por Membrana Extracorpórea , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/cirurgia , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Volume Sistólico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Resultado do Tratamento , Função Ventricular Esquerda
7.
J Pharmacol Exp Ther ; 370(2): 182-196, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085699

RESUMO

Ectoenzyme CD38 is increased on lymphocytes in response to an antigenic challenge and it is hypothesized that targeting these activated lymphocytes could ameliorate pathologic activities in autoimmune diseases. The cynomolgus monkey is an appropriate model for assessing potential effects of targeting CD38 in humans because these species exhibit similar expression profiles. TAK-079 is a human monoclonal antibody (IgG1 λ ) that binds to CD38 and lyses bound cells by complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. TAK-079 binds to monkey CD38 with an affinity at EC50 4.5 nM, and the potential activity of TAK-079 was investigated in a monkey collagen-induced arthritis model of autoimmune disease. Prophylactic administration of TAK-079 (3 mg/kg i.v. weekly) was well tolerated and prevented arthritis development compared with vehicle-treated control animals, which exhibited progressive disease with radiographic damage and worsening clinical scores over the study course. Therapeutic treatment of arthritic monkeys with TAK-079 (3 mg/kg i.v. weekly) was also well tolerated and reduced disease progression and symptoms. Arthritis scores and joint swelling were significantly lower than the vehicle control, accompanied by decreases in blood levels of C-reactive protein, alkaline phosphatase, and natural killer, B, and T cells. Histopathology, morphometry, and radiology revealed significantly less joint damage in animals exposed prophylactically to TAK-079 treatment compared with vehicle-treated animals and significantly less damage in animals treated therapeutically with TAK-079 or dexamethasone (0.1 mg/kg oral gavage daily), illustrating potential disease-modifying activity. In conclusion, these data indicate that depletion of CD38-expressing cells could be a therapeutic mechanism for treating autoimmune diseases. SIGNIFICANCE STATEMENT: This study demonstrates that targeting CD38-expressing leukocytes with a cytolytic antibody can ameliorate autoimmune disease in cynomolgus monkeys. The study gives a unique perspective into this therapeutic strategy because the three other anti-CD38 cytolytic antibodies in clinical development (daratumumab, isatuximab, and MOR202) cannot be tested in similar models because they do not crossreact with CD38 expressed by new world primates.


Assuntos
ADP-Ribosil Ciclase 1/metabolismo , Anticorpos Monoclonais/imunologia , Artrite Experimental/imunologia , Linfócitos B/metabolismo , Regulação da Expressão Gênica/imunologia , Células Matadoras Naturais/metabolismo , Linfócitos T/metabolismo , ADP-Ribosil Ciclase 1/imunologia , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Linfócitos B/imunologia , Células CHO , Cricetulus , Progressão da Doença , Células Matadoras Naturais/imunologia , Macaca fascicularis , Linfócitos T/imunologia
8.
J Exp Bot ; 70(15): 3969-3979, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31120500

RESUMO

Artemisinin is a sesquiterpene lactone produced by the Chinese traditional herb Artemisia annua and is used for the treatment of malaria. It is known that salicylic acid (SA) can enhance artemisinin content but the mechanism by which it does so is not known. In this study, we systematically investigated a basic leucine zipper family transcription factor, AaTGA6, involved in SA signaling to regulate artemisinin biosynthesis. We found specific in vivo and in vitro binding of the AaTGA6 protein to a 'TGACG' element in the AaERF1 promoter. Moreover, we demonstrated that AaNPR1 can interact with AaTGA6 and enhance its DNA-binding activity to its cognate promoter element 'TGACG' in the promoter of AaERF1, thus enhancing artemisinin biosynthesis. The artemisinin contents in AaTGA6-overexpressing and RNAi transgenic plants were increased by 90-120% and decreased by 20-60%, respectively, indicating that AaTGA6 plays a positive role in artemisinin biosynthesis. Importantly, heterodimerization with AaTGA3 significantly inhibits the DNA-binding activity of AaTGA6 and plays a negative role in target gene activation. In conclusion, we demonstrate that binding of AaTGA6 to the promoter of the artemisinin-regulatory gene AaERF1 is enhanced by AaNPR1 and inhibited by AaTGA3. Based on these findings, AaTGA6 has potential value in the genetic engineering of artemisinin production.


Assuntos
Artemisia annua/metabolismo , Artemisininas/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Artemisia annua/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas/genética
9.
New Phytol ; 218(2): 567-578, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29377155

RESUMO

Glandular trichomes and cuticles are both specialized structures that cover the epidermis of aerial plant organs. The former are commonly regarded as 'biofactories' for producing valuable natural products. The latter are generally considered as natural barriers for defending plants against abiotic and biotic stresses. However, the regulatory network for their formation and relationship remains largely elusive. Here we identify a homeodomain-leucine zipper (HD-ZIP) IV transcription factor, AaHD8, directly promoting the expression of AaHD1 for glandular trichome initiation in Artemisia annua. We found that AaHD8 positively regulated leaf cuticle development in A. annua via controlling the expression of cuticle-related enzyme genes. Furthermore, AaHD8 interacted with a MIXTA-like protein AaMIXTA1, a positive regulator of trichome initiation and cuticle development, forming a regulatory complex and leading to enhanced transcriptional activity in regulating the expression of AaHD1 and cuticle development genes. Our results reveal a molecular mechanism by which a novel HD-ZIP IV/MIXTA complex plays a significant role in regulating epidermal development, including glandular trichome initiation and cuticle formation.


Assuntos
Artemisia annua/crescimento & desenvolvimento , Complexos Multiproteicos/metabolismo , Epiderme Vegetal/crescimento & desenvolvimento , Proteínas de Plantas/metabolismo , Tricomas/crescimento & desenvolvimento , Artemisia annua/genética , Artemisia annua/ultraestrutura , Sequência de Bases , Vias Biossintéticas , Regulação da Expressão Gênica de Plantas , Modelos Biológicos , Epiderme Vegetal/genética , Epiderme Vegetal/ultraestrutura , Proteínas de Plantas/genética , Ligação Proteica , Transcrição Gênica , Tricomas/genética , Tricomas/ultraestrutura
10.
New Phytol ; 217(1): 261-276, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28940606

RESUMO

The glandular secretory trichomes (GSTs) on Artemisia annua leaves have the capacity to secrete and store artemisinin, a compound which is the most effective treatment for uncomplicated malaria. An effective strategy to improve artemisinin content is therefore to increase the density of GSTs in A. annua. However, the formation mechanism of GSTs remains poorly understood. To explore the mechanisms of GST initiation in A. annua, we screened myeloblastosis (MYB) transcription factor genes from a GST transcriptome database and identified a MIXTA transcription factor, AaMIXTA1, which is expressed predominantly in the basal cells of GST in A. annua. Overexpression and repression of AaMIXTA1 resulted in an increase and decrease, respectively, in the number of GSTs as well as the artemisinin content in transgenic plants. Transcriptome analysis and cuticular lipid profiling showed that AaMIXTA1 is likely to be responsible for activating cuticle biosynthesis. In addition, dual-luciferase reporter assays further demonstrated that AaMIXTA1 could directly activate the expression of genes related to cuticle biosynthesis. Taken together, AaMIXTA1 regulated cuticle biosynthesis and prompted GST initiation without any abnormal impact on the morphological structure of the GSTs and so provides a new way to improve artemisinin content in this important medicinal plant.


Assuntos
Artemisia annua/metabolismo , Artemisininas/metabolismo , Fatores de Transcrição/metabolismo , Tricomas/metabolismo , Sequência de Aminoácidos , Artemisia annua/genética , Artemisia annua/ultraestrutura , Regulação da Expressão Gênica de Plantas , Especificidade de Órgãos , Filogenia , Epiderme Vegetal/genética , Epiderme Vegetal/metabolismo , Epiderme Vegetal/ultraestrutura , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Alinhamento de Sequência , Fatores de Transcrição/genética , Tricomas/genética , Tricomas/ultraestrutura
11.
Xenobiotica ; 48(11): 1173-1183, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29098941

RESUMO

1. Red blood cell (RBC) partitioning is important in determining pharmacokinetic and pharmacodynamic properties of a compound; however, active transport across RBC membranes is not well understood, particularly without transporter-related cell membrane proteomics data. 2. In this study, we quantified breast cancer resistance protein (BCRP/Bcrp) and MDR1/P-glycoprotein (P-gp) protein expression in RBCs from humans, monkeys, dogs, rats and mice using nanoLC/MS/MS, and evaluated their effect on RBC partitioning and plasma exposure of their substrates. BCRP-specific substrate Cpd-1 and MDR1-specific substrate Cpd-2 were characterized using Caco-2 Transwell® system and then administered to Bcrp or P-gp knockout mice. 3. The quantification revealed BCRP/Bcrp but not MDR1/P-gp to be highly expressed on RBC membranes. The knockout mouse study indicated BCRP/Bcrp pumps the substrate out of RBCs, lowering its partitioning and thus preventing binding to intracellular targets. This result was supported by a Cpd-1 and Bcrp inhibitor ML753286 drug-drug interaction (DDI) study in mice. Because of enhanced partitioning of Cpd-1 into RBCs after BCRP/Bcrp inhibition, Cpd-1 plasma concentration changed much less extent with genetic or chemical knockout of Bcrp albeit marked blood concentration increase, suggesting less DDI effect. 4. This finding is fundamentally meaningful to RBC partitioning, pharmacokinetics and DDI studies of BCRP-specific substrates.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Membrana Eritrocítica/metabolismo , Proteínas de Neoplasias/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Células CACO-2 , Cromatografia Líquida , Interações Medicamentosas , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Humanos , Macaca fascicularis , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas de Neoplasias/antagonistas & inibidores , Ratos , Espectrometria de Massas em Tandem , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATP
12.
New Phytol ; 214(1): 304-316, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28001315

RESUMO

Artemisinin is a type of sesquiterpene lactone well known as an antimalarial drug, and is specifically produced in glandular trichomes of Artemisia annua. However, the regulatory network for the artemisinin biosynthetic pathway remains poorly understood. Exploration of trichome-specific transcription factors would facilitate the elucidation of regulatory mechanism of artemisinin biosynthesis. The WRKY transcription factor GLANDULAR TRICHOME-SPECIFIC WRKY 1 (AaGSW1) was cloned and analysed in A. annua. AaGSW1 exhibited similar expression patterns to the trichome-specific genes of the artemisinin biosynthetic pathway and AP2/ERF transcription factor AaORA. A ß-glucuronidase (GUS) staining assay further demonstrated that AaGSW1 is a glandular trichome-specific transcription factor. AaGSW1 positively regulates CYP71AV1 and AaORA expression by directly binding to the W-box motifs in their promoters. Overexpression of AaGSW1 in A. annua significantly improves artemisinin and dihydroartemisinic acid contents; moreover, AaGSW1 can be directly regulated by AaMYC2 and AabZIP1, which are positive regulators of jasmonate (JA)- and abscisic acid (ABA)-mediated artemisinin biosynthetic pathways, respectively. These results demonstrate that AaGSW1 is a glandular trichome-specific WRKY transcription factor and a positive regulator in the artemisinin biosynthetic pathway. Moreover, we propose that two trifurcate feed-forward pathways involving AaGSW1, CYP71AV1 and AaMYC2/AabZIP1 function in the JA/ABA response in A. annua.


Assuntos
Artemisia annua/metabolismo , Artemisininas/metabolismo , Vias Biossintéticas , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Artemisia annua/genética , Vias Biossintéticas/genética , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Glucuronidase/metabolismo , Modelos Biológicos , Especificidade de Órgãos , Oxilipinas/metabolismo , Filogenia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Ligação Proteica/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica , Tricomas/metabolismo
13.
New Phytol ; 213(3): 1145-1155, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27659595

RESUMO

Glandular trichomes are generally considered biofactories that produce valuable chemicals. Increasing glandular trichome density is a very suitable way to improve the productivity of these valuable metabolites, but little is known about the regulation of glandular trichome formation. Phytohormone jasmonate (JA) promotes glandular trichome initiation in various plants, but its mechanism is also unknown. By searching transcription factors regulated by JA in Artemisia annua, we identified a novel homeodomain-leucine zipper transcription factor, HOMEODOMAIN PROTEIN 1 (AaHD1), which positively controls both glandular and nonglandular trichome initiations. Overexpression of AaHD1 in A. annua significantly increased glandular trichome density without harming plant growth. Consequently, the artemisinin content was improved. AaHD1 interacts with A. annua jasmonate ZIM-domain 8 (AaJAZ8), which is a repressor of JA, thereby resulting in decreased transcriptional activity. AaHD1 knockdown lines show decreased sensitivity to JA on glandular trichome initiation, which indicates that AaHD1 plays an important role in JA-mediated glandular trichome initiation. We identified a new transcription factor that promotes A. annua glandular trichome initiation and revealed a novel molecular mechanism by which a homeodomain protein transduces JA signal to promote glandular trichome initiation. Our results also suggested a connection between glandular and nonglandular trichome formations.


Assuntos
Artemisia annua/embriologia , Artemisia annua/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Proteínas de Plantas/metabolismo , Tricomas/embriologia , Tricomas/metabolismo , Artemisia annua/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Modelos Biológicos , Organogênese/efeitos dos fármacos , Filogenia , Folhas de Planta/ultraestrutura , Proteínas de Plantas/química , Plantas Geneticamente Modificadas , Domínios Proteicos , Transcrição Gênica/efeitos dos fármacos , Tricomas/efeitos dos fármacos , Tricomas/ultraestrutura
14.
Bioconjug Chem ; 28(11): 2715-2728, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28937754

RESUMO

Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains. A new ELP nanoparticle (ISR) was synthesized that includes the canonical integrin-targeting ligand (Arg-Gly-Asp, RGD). FSI and ISR mixed in a 1:1 molar ratio coassemble into bifunctional nanoparticles containing both the FKBP domain for Rapa loading and the RGD ligand for integrin binding. Coassembled nanoparticles were evaluated for bifunctionality by performing in vitro cell-binding and drug-retention assays and in vivo MDA-MB-468 breast tumor regression and tumor-accumulation studies. The bifunctional nanoparticle demonstrated superior cell target binding and similar drug retention to FSI; however, it enhanced the formulation potency, such that tumor growth was suppressed at a 3-fold lower dose compared to an untargeted FSI-Rapa control. This data suggests that ELP-mediated scaffolds are useful tools for generating multifunctional nanomedicines with potential activity in cancer.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Portadores de Fármacos/química , Elastina/química , Integrinas/metabolismo , Sirolimo/administração & dosagem , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Mama/efeitos dos fármacos , Mama/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Peptídeos/química , Sirolimo/farmacocinética , Sirolimo/farmacologia , Sirolimo/uso terapêutico
15.
Plant Cell Physiol ; 57(3): 588-602, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26858285

RESUMO

There are many biosynthetic pathways competing for the metabolic flux with the artemisinin biosynthetic pathway in Artemisia annua L. To study the relationship between genes encoding enzymes at branching points and the artemisinin biosynthetic pathway, ß-caryophyllene, ß-farnesene and squalene were sprayed on young seedlings of A. annua. Transient expression assays indicated that the transcription levels of ß-caryophyllene synthase (CPS), ß-farnesene synthase (BFS) and squalene synthase (SQS) were inhibited by ß-caryophyllene, ß-farnesene and squalene, respectively, while expression of some artemisinin biosynthetic pathway genes increased. Thus, inhibition of these genes encoding enzymes at branching points may be helpful to improve the artemisinin content. For further study, the expression levels of four branch pathway genes CPS, BFS, germacrene A synthase (GAS) and SQS were down-regulated by the antisense method in A. annua. In anti-CPS transgenic plants, mRNA levels of BFS and ADS were increased, and the contents of ß-farnesene, artemisinin and dihydroartemisinic acid (DHAA) were increased by 212, 77 and 132%, respectively. The expression levels of CPS, SQS, GAS, amorpha-4,11-diene synthase (ADS), amorphadiene 12-hydroxylase (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1) were increased in anti-BFS transgenic plants and, at the same time, the contents of artemisinin and DHAA were increased by 77% and 54%, respectively, and the content of squalene was increased by 235%. In anti-GAS transgenic plants, mRNA levels of CPS, BFS, ADS and ALDH1 were increased. The contents of artemisinin and DHAA were enhanced by 103% and 130%, respectively. In anti-SQS transgenic plants, the transcription levels of BFS, GAS, CPS, ADS, CYP71AV1 and ALDH1 were all increased. Contents of artemisinin and DHAA were enhanced by 71% and 223%, respectively, while ß-farnesene was raised to 123%. The mRNA level of artemisinic aldehyde Δ11(13) reductase (DBR2) had changed little in almost all transgenic plants.


Assuntos
Artemisia annua/metabolismo , Artemisininas/metabolismo , Vias Biossintéticas , Lactonas/metabolismo , Artemisia annua/efeitos dos fármacos , Artemisia annua/enzimologia , Artemisia annua/genética , Artemisininas/química , Vias Biossintéticas/efeitos dos fármacos , Vias Biossintéticas/genética , Farnesil-Difosfato Farnesiltransferase/antagonistas & inibidores , Farnesil-Difosfato Farnesiltransferase/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Lactonas/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Sesquiterpenos Policíclicos , Pirofosfatases/antagonistas & inibidores , Pirofosfatases/metabolismo , Sesquiterpenos/farmacologia , Esqualeno/farmacologia , Terpenos/farmacologia
16.
Biotechnol Appl Biochem ; 63(6): 834-840, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26340706

RESUMO

Artemisinin, a sesquiterpene lactone isolated from Artemisia annua L. (sweet wormwood), is extensively used in the treatment of malaria. In order to better understand the metabolism of terpenes in A. annua and the influence of terpene synthases on artemisinin yield, the expression pattern of a monoterpene alcohol dehydrogenase (ADH2) has been studied using transgenic plants expressing promoter-ß-glucuronidase (GUS) fusion. ADH2 played a major role in monoterpenoid biosynthesis including carveol, borneol, and artemisia ketone through in vitro biochemical analysis. In this study, the ADH2 promoter was cloned by the genome walking method. A number of putative cis-acting elements were predicted in promoter region, suggesting that the ADH2 is driven by a complex regulation mechanism. ADH2 gene was highly expressed in old leaves, whereas the artemisinin biosynthetic genes were mainly expressed in bud and young leaves. The expression of ADH2 gene increased quickly during leaf development, revealed by qRT-PCR. GUS expression analysis in different tissues of transgenic A. annua demonstrates that ADH2 expression is exclusively located to T-shaped trichome, not glandular secretory trichome.


Assuntos
Alquil e Aril Transferases/genética , Artemisia annua/genética , Regulação da Expressão Gênica de Plantas , Glucuronidase/genética , Regiões Promotoras Genéticas/genética , Proteínas Recombinantes de Fusão/genética , Tricomas/genética , Artemisia annua/citologia , Sequência de Bases , Clonagem Molecular , Genômica , Especificidade de Órgãos , Folhas de Planta/genética , Plantas Geneticamente Modificadas
17.
Polymers (Basel) ; 16(4)2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38399919

RESUMO

The emergence of novel e-textile materials that combine the inherent qualities of the textile substrate (lightweight, soft, breathable, durable, etc.) with the functionality of micro/nano-electronic materials (conductive, dielectric, sensing, etc.) has resulted in a trend toward miniaturization, integration, and intelligence in new electronic devices. However, the formation of a conductive network by micro/nano-conductive materials on textiles necessitates high-temperature sintering, which inevitably causes substrate aging and component damage. Herein, a bis-hydroxy-imidazolium chloride salt as a hard segment to synthesize a waterborne polyurethane (WPU) adhesive is designed and prepared. When used in nano-silver-based printing coatings, it offers strong adherence for coatings, reaching 16 N cm-1; on the other hand, the introduction of chloride ions enables low-temperature (60 °C) chemical sintering to address the challenge of secondary treatment and high-temperature sintering (>150 °C). Printed into flexible circuits, the resistivity can be controlled by the content of imidazolium salts anchored in the molecular chain of the WPU from a maximum resistivity of 3.1 × 107 down to 5.8 × 10-5 Ω m, and it can conduct a Bluetooth-type finger pulse detector with such low resistivity. As a flexible circuit, it also offers high stability against washing and adhesion, which the resistivity only reduces less than 20% after washing 10 times and adhesion. Owing to the adjustability of the resistivity, we fabricated an all-textile flexible pressure sensor that accurately differentiates different external pressures (min. 10 g, ~29 Pa), recognizes forms, and detects joint motions (finger bending and wrist flexion).

18.
Math Biosci Eng ; 20(8): 14899-14919, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-37679164

RESUMO

The ongoing emergence of COVID-19 and the maturation of cold chain technology, have aided in the rapid development of the fresh produce e-commerce industry. Taking into account the characteristics of consumers' demand for fresh products, this paper constructs a location allocation model of a front warehouse for fresh e-commerce with the objective of minimizing the total cost. An improved immune optimization algorithm is proposed in this paper, and the effectiveness of the proposed algorithm is demonstrated by a real case study. The results show that the improved immune optimization algorithm outperforms the traditional genetic algorithm in terms of solution accuracy; the proposed location model can effectively help fresh produce e-commerce enterprises open new front-end warehouses when demand is increasing, as well as provide optimal economic decision-making for front warehouse layout.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Comércio , Indústrias , Algoritmos
19.
Sci Data ; 10(1): 539, 2023 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587134

RESUMO

The carnivorous gastropod Rapana venosa (Valenciennes, 1846) is one of the most notorious ecological invaders worldwide. Here, we present the first high-quality chromosome-scale reference R. venosa genome obtained via PacBio sequencing, Illumina paired-end sequencing, and high-throughput chromosome conformation capture scaffolding. The assembled genome has a size of 2.30 Gb, with a scaffold N50 length of 64.63 Mb, and is anchored to 35 chromosomes. It contains 29,649 protein-coding genes, 77.22% of which were functionally annotated. Given its high heterozygosity (1.41%) and large proportion of repeat sequences (57.72%), it is one of the most complex genome assemblies. This chromosome-level genome assembly of R. venosa is an important resource for understanding molluscan evolutionary adaption and provides a genetic basis for its biological invasion control.


Assuntos
Evolução Biológica , Genoma , Caramujos , Animais , Caramujos/genética
20.
Integr Zool ; 18(3): 506-517, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36063563

RESUMO

Metamorphosis is the short developmental stage characterized by dramatic ontogenetic changes that occurs in most animals. However, this important process remains largely unclear in marine invertebrates. In this study, we performed the sequential RNA sequencing of a representative mollusk, the rapa whelk (Rapana venosa), that is undergoing metamorphosis and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to investigate the overall and dynamic transcriptome responses. The results revealed that the expression of cytochrome P450 2A and 3A were upregulated during metamorphosis, while the expression of H/ACA ribonucleoproteins increased 4 h after metamorphosis induction (M4 stage), indicating that R. venosa mainly responded to the pelagobenthic changes. At the M24 stage, the enrichment of V-type proton ATPase and insulin indicated the complete development of secretory organs and initiation of hormone secretion. Furthermore, at the M48 stage, the enrichment of zinc metalloproteinase and conotoxin indicated a well-developed predation system that requires exogenous nutrition. Finally, during the PL stage, the genes associated with growth control were highly enriched, implying that R. venosa had completed metamorphosis and has entered the period of rapid growth. Therefore, our study provides useful transcriptomic resources for R. venosa and contributes new insights that may assist in elucidating the mechanisms underlying metamorphosis in marine invertebrates.


Assuntos
Gastrópodes , Animais , Gastrópodes/genética , Transcriptoma , Perfilação da Expressão Gênica , Organismos Aquáticos
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