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1.
Cell ; 148(4): 780-91, 2012 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-22341448

RESUMO

The Tasmanian devil (Sarcophilus harrisii), the largest marsupial carnivore, is endangered due to a transmissible facial cancer spread by direct transfer of living cancer cells through biting. Here we describe the sequencing, assembly, and annotation of the Tasmanian devil genome and whole-genome sequences for two geographically distant subclones of the cancer. Genomic analysis suggests that the cancer first arose from a female Tasmanian devil and that the clone has subsequently genetically diverged during its spread across Tasmania. The devil cancer genome contains more than 17,000 somatic base substitution mutations and bears the imprint of a distinct mutational process. Genotyping of somatic mutations in 104 geographically and temporally distributed Tasmanian devil tumors reveals the pattern of evolution and spread of this parasitic clonal lineage, with evidence of a selective sweep in one geographical area and persistence of parallel lineages in other populations.


Assuntos
Neoplasias Faciais/veterinária , Instabilidade Genômica , Marsupiais/genética , Mutação , Animais , Evolução Clonal , Espécies em Perigo de Extinção , Neoplasias Faciais/epidemiologia , Neoplasias Faciais/genética , Neoplasias Faciais/patologia , Feminino , Estudo de Associação Genômica Ampla , Masculino , Dados de Sequência Molecular , Tasmânia/epidemiologia
2.
Small ; 20(10): e2305678, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37875729

RESUMO

Small-scale and flexible acoustic probes are more desirable for exquisite objects like human bodies and complex-shaped components than conventional rigid ones. Herein, a thin-film flexible acoustic sensor (FA-TES) that can detect ultra-broadband acoustic signals in multiple applications is proposed. The device consists of two thin copper-coated polyvinyl chloride films, which are stimulated by acoustic waves and contact each other to generate the triboelectric signal. Interlocking nanocolumn arrays fabricated on the friction surfaces are regarded as a highly adaptive spacer enabling this device to respond to ultra-broadband acoustic signals (100 Hz-4 MHz) and enhance sensor sensitivity for film weak vibration. Benefiting from the characteristics of high shape adaptability and ultrawide response range, the FA-TES can precisely sense human physiological sounds and voice (≤10 kHz) for laryngeal health monitoring and interaction in real-time. Moreover, the FA-TES flexibly arranged on a 3D-printed vertebra model can effectively and accurately diagnose the inner defect by ultrasonic testing (≥1 MHz). It envisions that this work can provide new ideas for flexible acoustic sensor designs and optimize real-time acoustic detections of human bodies and complex components.


Assuntos
Acústica , Ultrassom , Humanos , Ultrassonografia , Som , Fricção
3.
Nat Chem Biol ; 18(10): 1065-1075, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35788181

RESUMO

Aldehyde dehydrogenases (ALDHs) are promising cancer drug targets, as certain isoforms are required for the survival of stem-like tumor cells. We have discovered selective inhibitors of ALDH1B1, a mitochondrial enzyme that promotes colorectal and pancreatic cancer. We describe bicyclic imidazoliums and guanidines that target the ALDH1B1 active site with comparable molecular interactions and potencies. Both pharmacophores abrogate ALDH1B1 function in cells; however, the guanidines circumvent an off-target mitochondrial toxicity exhibited by the imidazoliums. Our lead isoform-selective guanidinyl antagonists of ALDHs exhibit proteome-wide target specificity, and they selectively block the growth of colon cancer spheroids and organoids. Finally, we have used genetic and chemical perturbations to elucidate the ALDH1B1-dependent transcriptome, which includes genes that regulate mitochondrial metabolism and ribosomal function. Our findings support an essential role for ALDH1B1 in colorectal cancer, provide molecular probes for studying ALDH1B1 functions and yield leads for developing ALDH1B1-targeting therapies.


Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Aldeído Desidrogenase/química , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Família Aldeído Desidrogenase 1 , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Aldeídos , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Guanidinas , Humanos , Sondas Moleculares , Proteoma/genética
4.
Ecotoxicol Environ Saf ; 276: 116335, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38626603

RESUMO

Urethane hydrolase can degrade the carcinogen ethyl carbamate (EC) in fermented food, but its stability and activity limit its application. In this study, a mutant G246A and a double mutant N194V/G246A with improved cpUH activity and stability of Candida parapsilosis were obtained by site-directed mutagenesis. The catalytic efficiency (Kcat/Km) of mutant G246A and double mutant N194V/G246A are 1.95 times and 1.88 times higher than that of WT, respectively. In addition, compared with WT, the thermal stability and pH stability of mutant G246A and double mutant N194V/G246A were enhanced. The ability of mutant G246A and double mutant N194V/G246A to degrade EC in rice wine was also stronger than that of WT. The mutation increased the stability of the enzyme, as evidenced by decreased root mean square deviation (RMSD) and increased hydrogen bonds between the enzyme and substrate by molecular dynamics simulation and molecular docking analysis. The molecule modification of new cpUH promotes the industrial process of EC degradation.


Assuntos
Candida parapsilosis , Etanol , Oryza , Vinho , Concentração de Íons de Hidrogênio , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/genética , Etanol/metabolismo , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Uretana/metabolismo , Simulação de Dinâmica Molecular , Biodegradação Ambiental , Mutação , Estabilidade Enzimática , População do Leste Asiático
5.
Sensors (Basel) ; 23(7)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37050777

RESUMO

Recent advances in flexible pressure sensors have fueled increasing attention as promising technologies with which to realize human epidermal pulse wave monitoring for the early diagnosis and prevention of cardiovascular diseases. However, strict requirements of a single sensor on the arterial position make it difficult to meet the practical application scenarios. Herein, based on three single-electrode sensors with small area, a 3 × 1 flexible pressure sensor array was developed to enable measurement of epidermal pulse waves at different local positions of radial artery. The designed single sensor holds an area of 6 × 6 mm2, which mainly consists of frosted microstructured Ecoflex film and thermoplastic polyurethane (TPU) nanofibers. The Ecoflex film was formed by spinning Ecoflex solution onto a sandpaper surface. Micropatterned TPU nanofibers were prepared on a fluorinated ethylene propylene (FEP) film surface using the electrospinning method. The combination of frosted microstructure and nanofibers provides an increase in the contact separation of the tribopair, which is of great benefit for improving sensor performance. Due to this structure design, the single small-area sensor was characterized by pressure sensitivity of 0.14 V/kPa, a response time of 22 ms, a wide frequency band ranging from 1 to 23 Hz, and stability up to 7000 cycles. Given this output performance, the fabricated sensor can detect subtle physiological signals (e.g., respiration, ballistocardiogram, and heartbeat) and body movement. More importantly, the sensor can be utilized in capturing human epidermal pulse waves with rich details, and the consistency of each cycle in the same measurement is as high as 0.9987. The 3 × 1 flexible sensor array is employed to acquire pulse waves at different local positions of the radial artery. In addition, the time domain parameters including pulse wave transmission time (PTT) and pulse wave velocity (PWV) can be obtained successfully, which holds promising potential in pulse-based cardiovascular system status monitoring.


Assuntos
Nanofibras , Poliuretanos , Humanos , Nanofibras/química , Análise de Onda de Pulso , Artéria Radial/fisiologia
6.
J Recept Signal Transduct Res ; 42(3): 251-260, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33858297

RESUMO

Papillary thyroid cancer (PTC) is a common tumor malignancy of the endocrine system worldwide. Recently, circular RNAs (circRNAs) have been reported to participate in diverse pathological processes, especially in tumorigenesis. However, the functional role and mechanism of circRNA pleckstrin and Sec7 domain containing 3 (circ-PSD3) in PTC are still unclear. In this study, qRT-PCR results showed that circ-PSD3 was significantly upregulated in PTC tissues and cell lines. Meanwhile, circ-PSD3 overexpression was positively associated with larger tumor size, TNM stage, and lymph node metastasis. Knockdown of circ-PSD3 suppressed the proliferation and invasion of PTC cells. Besides, circ-PSD3 interacted with miR-7-5p to reduce its expression, and methyltransferase like 7B (METTL7B) was verified as a target gene of miR-7-5p. Functionally, inhibition of circ-PSD3 impeded PTC cell proliferation and invasion via targeting miR-7-5p to downregulate METTL7B expression. Taken together, silencing of circ-PSD3 hampered the proliferation and invasion of PTC cells via upregulating the inhibitory effect of miR-7-5p on METTL7B expression. Therefore, circ-PSD3 could be a potential diagnostic biomarker or molecular treatment target for PTC.


Assuntos
MicroRNAs , Neoplasias da Glândula Tireoide , Proteínas de Transporte , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
7.
Sensors (Basel) ; 23(1)2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36616646

RESUMO

Flexible pressure sensors with the capability of monitoring human vital signs show broad application prospects in personalized healthcare. In this work, a hair-based flexible pressure sensor (HBPS) consisting of lost hair and polymer films was proposed for the continuous monitoring of the human epidermal arterial pulse waveform. A macroscale mesh structure formed by lost hair provides a simplified spacer that endows the triboelectric-based flexible pressure sensor with sufficient contact-separation space. Based on this mesh structure design, the hair-based flexible pressure sensor can respond to the slight pressure change caused by an object with 5 mg weight and hold a stable output voltage under 1-30 Hz external pressure excitation. Additionally, the hair-based flexible pressure sensor showed great sensitivity (0.9 V/kPa) and decent stability after 4500 cycles of operation. Given these compelling features, the HBPS can successfully measure the human epidermal arterial pulses with obvious details at different arteries. The proposed HBPS can also be used to monitor the pulse signals of different subjects. Furthermore, the three different pulse wave transmission time (PTT) values (PTT-foot, PTT-middle, and PTT-peak) can be obtained by simultaneously monitoring human pulse and electrocardiogram signals, which has enormous application potential for assessing cardiovascular system health.


Assuntos
Pulso Arterial , Telas Cirúrgicas , Humanos , Frequência Cardíaca , Artérias , Cabelo
8.
Molecules ; 27(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36234767

RESUMO

The zebrafish is one of the most widely adopted animal models in both basic and translational research. This popularity of the zebrafish results from several advantages such as a high degree of similarity to the human genome, the ease of genetic and chemical perturbations, external fertilization with high fecundity, transparent and fast-developing embryos, and relatively low cost-effective maintenance. In particular, body translucency is a unique feature of zebrafish that is not adequately obtained with other vertebrate organisms. The animal's distinctive optical clarity and small size therefore make it a successful model for optical modulation and observation. Furthermore, the convenience of microinjection and high embryonic permeability readily allow for efficient delivery of large and small molecules into live animals. Finally, the numerous number of siblings obtained from a single pair of animals offers large replicates and improved statistical analysis of the results. In this review, we describe the development of opto-chemical tools based on various strategies that control biological activities with unprecedented spatiotemporal resolution. We also discuss the reported applications of these tools in zebrafish and highlight the current challenges and future possibilities of opto-chemical approaches, particularly at the single cell level.


Assuntos
Peixe-Zebra , Animais , Humanos , Microinjeções
9.
Mol Carcinog ; 60(1): 25-37, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33283877

RESUMO

BACKGROUND: Thyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet. METHODS: TC cell lines (IHH4 and TPC-1) were used. Flow cytometry was used to identify the surface marker of M2-like tumor-associated macrophages (TAMs) from cell culture. Quantitative real-time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/ß-catenin pathway, and proliferation/epithelial-mesenchymal transition (EMT)-related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and ß-catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice. RESULTS: Coculture with M2-like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation-related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/ß-catenin signaling pathway, and suppressed EMT and proliferation-related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model. CONCLUSION: M2-like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing ß-catenin activation.


Assuntos
Neoplasias da Glândula Tireoide/patologia , Macrófagos Associados a Tumor/patologia , Via de Sinalização Wnt , Proteína Wnt1/metabolismo , Proteína Wnt3A/metabolismo , Animais , Desdiferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Feminino , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/patologia , Metástase Neoplásica/patologia , Neoplasias da Glândula Tireoide/metabolismo , Macrófagos Associados a Tumor/metabolismo
10.
J Cell Biochem ; 119(4): 3280-3292, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29125882

RESUMO

Spinal cord injuries are common and troublesome disorder, which is mediated by various signal pathways and mechanisms. MK2 is also involved in numerous inflammatory diseases including spinal cord injury. The role of microRNA-137 (miR-137) and its detailed working mechanism in spinal cord injuries remain unclear. In the present study, we found that an elevated MK2 but a decreased miR-137 was expressed in serum specimens of patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Meanwhile, we suggested that upregulation of miR-137 could inhibit the expression of TNF-α and IL-6, two markers of inflammatory response after SCI, and apoptosis in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Furthermore, we verified that MK2 was a direct target of miR-137 thorough a constructed luciferase assay. Even further, we elucidated that miR-137 could suppress the inflammatory response and apoptosis via negative regulation of MK2. Finally, through an animal model trial performed using mice, we demonstrated the protective effect of how miR-137 works on inflammatory response and apoptosis after spinal cord injury. Considering all the forementioned, our findings revealed that miR-137 inhibited inflammatory response and apoptosis after spinal cord injury via the targeting of MK2. The outcomes of the present study might indicate a new target in molecular treatment of SCI.


Assuntos
Astrócitos/citologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , Traumatismos da Medula Espinal/genética , Regiões 3' não Traduzidas , Animais , Apoptose , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Células HEK293 , Humanos , Peróxido de Hidrogênio/efeitos adversos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismos da Medula Espinal/metabolismo
11.
Chembiochem ; 19(12): 1232-1238, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29341391

RESUMO

The use of light to control the expression of genes and the activity of proteins is a rapidly expanding field. Whereas many of these approaches use fusion between a light-activable protein and the protein of interest to control the activity of the latter, it is also possible to control the activity of a protein by uncaging a specific ligand. In that context, controlling the activation of a protein fused to the modified estrogen receptor (ERT) by uncaging its ligand cyclofen-OH has emerged as a generic and versatile method to control the activation of proteins quantitatively, quickly, and locally in a live organism. We present that approach and its uses in a variety of physiological contexts.


Assuntos
Optogenética/métodos , Compostos Policíclicos/metabolismo , Receptores de Estrogênio/genética , Animais , Regulação da Expressão Gênica/efeitos da radiação , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Ligantes , Compostos Policíclicos/química , Receptores de Estrogênio/metabolismo , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
12.
J Autoimmun ; 68: 52-61, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26786119

RESUMO

MicroRNAs (miRNAs) regulate T cell development and function and the disruption of miRNAs in natural regulatory CD4(+) FOXP3(+) T cells (nTreg) leads to autoimmune disease in mice. To investigate miRNA expression in relation to autoimmune disease risk in humans we sequenced them in purified CD4(+) T cell subsets from individuals at high risk of type 1 diabetes (pre-T1D), as well as other healthy individuals. Differences in miRNA expression patterns were observed between specific T cell subsets and, within subsets, between pre-T1D and healthy individuals. Compared to healthy, naive CD4(+) T cells in pre-T1D displayed 32 differentially expressed miRNAs, potentially a template for altered miRNA expression in effector memory T cells in T1D. Naive nTreg in pre-T1D displayed two differentially expressed miRNAs, Let-7c and miR-15a. In contrast, nTreg activated in vivo displayed a large number of differentially expressed miRNAs, revealing a pro-inflammatory and FOXP3-repressive signature. Differential expression of specific miRNAs was also a signpost to altered T cell function. For example, in pre-T1D, increased expression of miR-26a in nTreg activated in vivo or in vitro was associated with decreased expression of its target, the histone methyltransferase EZH2. Chemical inhibition of EZH2 decreased the number of activated naïve nTreg and their expression of nTreg signature genes FOXP3 and TIGIT. Our findings demonstrate that miRNAs differentially expressed in CD4(+) T cell subsets are markers of risk and T cell dysfunction in T1D.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , MicroRNAs/genética , Biomarcadores , Análise por Conglomerados , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Biblioteca Gênica , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Ativação Linfocitária , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
13.
Malar J ; 15(1): 258, 2016 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-27149991

RESUMO

BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variants are encoded by var genes and mediate pathogenic cytoadhesion and antigenic variation in malaria. PfEMP1s can be broadly divided into three principal groups (A, B and C) and they contain conserved arrangements of functional domains called domain cassettes. Despite their tremendous diversity there is compelling evidence that a restricted subset of PfEMP1s is expressed in severe disease. In this study antibodies from patients with severe and uncomplicated malaria were compared for differences in reactivity with a range of PfEMP1s to determine whether antibodies to particular PfEMP1 domains were associated with severe or uncomplicated malaria. METHODS: Parts of expressed var genes in a severe malaria patient were identified by RNAseq and several of these partial PfEMP1 domains were expressed together with others from laboratory isolates. Antibodies from Papuan patients to these parts of multiple PfEMP1 proteins were measured. RESULTS: Patients with uncomplicated malaria were more likely to have antibodies that recognized PfEMP1 of Group C type and recognized a broader repertoire of group A and B PfEMP1s than patients with severe malaria. CONCLUSION: These data suggest that exposure to a broad range of group A and B PfEMP1s is associated with protection from severe disease in Papua, Indonesia.


Assuntos
Anticorpos Antiprotozoários/sangue , Malária Falciparum/imunologia , Proteínas de Protozoários/imunologia , Adolescente , Adulto , Pré-Escolar , Feminino , Humanos , Indonésia , Masculino , Adulto Jovem
14.
BMC Genomics ; 16: 535, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26194104

RESUMO

BACKGROUND: Major histocompatibility complex (MHC) class I genes are found in the genomes of all jawed vertebrates. The evolution of this gene family is closely tied to the evolution of the vertebrate genome. Family members are frequently found in four paralogous regions, which were formed in two rounds of genome duplication in the early vertebrates, but in some species class Is have been subject to additional duplication or translocation, creating additional clusters. The gene family is traditionally grouped into two subtypes: classical MHC class I genes that are usually MHC-linked, highly polymorphic, expressed in a broad range of tissues and present endogenously-derived peptides to cytotoxic T-cells; and non-classical MHC class I genes generally have lower polymorphism, may have tissue-specific expression and have evolved to perform immune-related or non-immune functions. As immune genes can evolve rapidly and are subject to different selection pressure, we hypothesised that there may be divergent, as yet unannotated or uncharacterised class I genes. RESULTS: Application of a novel method of sensitive genome searching of available vertebrate genome sequences revealed a new, extensive sub-family of divergent MHC class I genes, denoted as UT, which has not previously been characterized. These class I genes are found in both American and Australian marsupials, and in monotremes, at an evolutionary chromosomal breakpoint, but are not present in non-mammalian genomes and have been lost from the eutherian lineage. We show that UT family members are expressed in the thymus of the gray short-tailed opossum and in other immune tissues of several Australian marsupials. Structural homology modelling shows that the proteins encoded by this family are predicted to have an open, though short, antigen-binding groove. CONCLUSIONS: We have identified a novel sub-family of putatively non-classical MHC class I genes that are specific to marsupials and monotremes. This family was present in the ancestral mammal and is found in extant marsupials and monotremes, but has been lost from the eutherian lineage. The function of this family is as yet unknown, however, their predicted structure may be consistent with presentation of antigens to T-cells.


Assuntos
Evolução Molecular , Genes MHC Classe I , Marsupiais/genética , Monotremados/genética , Sequência de Aminoácidos , Animais , Austrália , Sequência de Bases , Genoma , Humanos , Filogenia
15.
Development ; 139(18): 3355-62, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22874920

RESUMO

All-trans retinoic acid (RA) is a key player in many developmental pathways. Most methods used to study its effects in development involve continuous all-trans RA activation by incubation in a solution of all-trans RA or by implanting all-trans RA-soaked beads at desired locations in the embryo. Here we show that the UV-driven photo-isomerization of 13-cis RA to the trans-isomer (and vice versa) can be used to non-invasively and quantitatively control the concentration of all-trans RA in a developing embryo in time and space. This facilitates the global or local perturbation of developmental pathways with a pulse of all-trans RA of known concentration or its inactivation by UV illumination. In zebrafish embryos in which endogenous synthesis of all-trans RA is impaired, incubation for as little as 5 minutes in 1 nM all-trans RA (a pulse) or 5 nM 13-cis RA followed by 1-minute UV illumination is sufficient to rescue the development of the hindbrain if performed no later than bud stage. However, if subsequent to this all-trans RA pulse the embryo is illuminated (no later than bud stage) for 1 minute with UV light (to isomerize, i.e. deactivate, all-trans RA), the rescue of hindbrain development is impaired. This suggests that all-trans RA is sequestered in embryos that have been transiently exposed to it. Using 13-cis RA isomerization with UV light, we further show that local illumination at bud stage of the head region (but not the tail) is sufficient to rescue hindbrain formation in embryos whose all-trans RA synthetic pathway has been impaired.


Assuntos
Rombencéfalo/embriologia , Rombencéfalo/metabolismo , Tretinoína/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Animais , Isotretinoína/química , Isotretinoína/metabolismo , Rombencéfalo/efeitos da radiação , Tretinoína/química , Raios Ultravioleta
16.
Biomed Chromatogr ; 29(8): 1167-72, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25582386

RESUMO

A sensitive, rapid and robust HPLC method with tandem mass spectrometry (HPLC/MS/MS) detection has been developed and validated for the quantification of sotalol in rat plasma. Plasma samples were precipitated with acetonitrile before analysis. The chromatographic separation was performed on an Atlantis hydrophilic interaction liquid chromatography Silica column (50 × 2.1 mm, 3 µm) with a gradient mobile phase of 10 mm NH4 COOH (containing 0.2% of formic acid) as buffer A and acetonitrile as mobile phase B. Sotalol (m/z 273.2 → 255.1) and atenolol (the internal standard, IS, m/z 267.2 → 190.1) were monitored under positive ionization mode with 5500 QTRAP. Retention time of sotalol and the IS were 2.69 and 3.43 min, respectively. The linear range was 5-500 nm based on the analysis of 0.1 mL of plasma. The intrabatch precision ranged from 1.2 to 6.1%, and the inter-batch precision was from 3.3 to 6.5%. The coefficient of variation of IS-normalized matrix factor was 7.6%. Experiments for stability were performed and the analyte was sufficiently stable. A run time of 6 min for each injection made it possible to analyze a high throughput of plasma samples. The assay was successfully applied to the determination of sotalol in rat plasma after a micro-dose oral administration.


Assuntos
Antagonistas Adrenérgicos beta/sangue , Antiarrítmicos/sangue , Sotalol/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida de Alta Pressão/economia , Cromatografia Líquida de Alta Pressão/métodos , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/economia
17.
Proc Natl Acad Sci U S A ; 108(17): 6999-7003, 2011 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-21444803

RESUMO

Schistosomiasis is an infectious disease caused by parasites of the phylum platyhelminthe. Here, we describe the identification and characterization of a Bcl-2-regulated apoptosis pathway in Schistosoma japonicum and S. mansoni. Genomic, biochemical, and cell-based mechanistic studies provide evidence for a tripartite pathway, similar to that in humans including BH3-only proteins that are inhibited by prosurvival Bcl-2-like molecules, and Bax/Bak-like proteins that facilitate mitochondrial outer-membrane permeabilization. Because Bcl-2 proteins have been successfully targeted with "BH3 mimetic" drugs, particularly in the treatment of cancer, we investigated whether schistosome apoptosis pathways could provide targets for future antischistosomal drug discovery efforts. Accordingly, we showed that a schistosome prosurvival protein, sjA, binds ABT-737, a well-characterized BH3 mimetic. A crystal structure of sjA bound to a BH3 peptide provides direct evidence for the feasibility of developing BH3 mimetics to target Bcl-2 prosurvival proteins in schistosomes, suggesting an alternative application for this class of drugs beyond cancer treatment.


Assuntos
Apoptose/fisiologia , Proteínas de Helminto/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Schistosoma japonicum/metabolismo , Schistosoma mansoni/metabolismo , Animais , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Cristalografia por Raios X , Proteínas de Helminto/antagonistas & inibidores , Proteínas de Helminto/genética , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Nitrofenóis/farmacologia , Fragmentos de Peptídeos/farmacologia , Piperazinas/farmacologia , Proteínas Proto-Oncogênicas/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/genética , Schistosoma japonicum/genética , Schistosoma mansoni/genética , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/genética , Esquistossomose Japônica/metabolismo , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/genética , Esquistossomose mansoni/metabolismo , Sulfonamidas/farmacologia
18.
Adv Healthc Mater ; 13(6): e2303479, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38010831

RESUMO

Sleep is critical to maintaining physical and mental health. Measuring physiological parameters to quantify sleep quality without uncomfortable user experience remains highly desired but a challenge. Here, this work develops a soft bioelectronic patch to perform simultaneous respiration and cardiovascular monitoring during sleep in a wearable and non-invasive manner. The soft bioelectronic patch system is mainly composed of a pressure sensor, a flexible printed circuit for signal processing, and a soft thermoplastic urethane mold for assembling different functional modules. The soft bioelectronic patch holds a sensitivity of >0.12 V kPa-1 and a remarkable low-frequency response from 0.5 to 15 Hz. It is demonstrated to continuously monitor respiration and heartbeat during the whole night, which could be harnessed for sleep monitoring and obstructive sleep apnea-hypopnea syndrome diagnosis. The reported soft bioelectronic patch represents a simple and convenient platform technology for sleep study.


Assuntos
Amidas , Processamento de Sinais Assistido por Computador , Monitorização Fisiológica , Carbamatos , Ésteres
19.
Animals (Basel) ; 14(6)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38540039

RESUMO

Uroteuthis edulis (U. edulis) is an important economic loliginid resource in the East China Sea (ECS). Its flexible life history traits enable the population to quickly adapt to changes in habitat. Understanding the early transport process helps us to grasp the habitat requirements of populations at key life history stages. In this study, particle tracing was used to simulate the early transport trajectories (within 120 days). The gradient forest method (GFM) and generalized additive mixed models (GAMMs) were used to analyze the key environmental variables that affect the early transport trajectories and the impact of environmental factors on the transport process, respectively. The results showed that spring stock tracers were transported to the northeast of the release area (Pengjiayu water) and the Pacific side of Japan. Summer stock tracers were transported to the north and northeast of the release area (Zhoushan island). Current velocity, salinity, and temperature were key environmental variables that affected the trace element ratios of spring stock at early life history stages. Mixed-layer depth (MLD), velocity, and chlorophyll a concentration (Chla) were key environmental variables for summer stock. Zonal velocity was positively correlated with the trace element ratio for spring and summer stock (0.14-0.16 m/s), while the meridional velocity showed an opposite correlation. The physical driving mechanisms of the Kuroshio warm current (or the Taiwan warm current) and the Yangtze River determine the paralarva retention location during early transportation. The differences in the dominant factors of the water environment in the retention area may affect the paralarva physiological functions and food availability. This study provides a scientific basis for a comprehensive understanding of the migration characteristics of U. edulis with different stocks.

20.
J Agric Food Chem ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598779

RESUMO

The microbial consortium FA12 that can release ferulic acid (FA) by fermenting distiller's grains was screened from Daqu. Taibaiella, Comamonadaceae, and Ochrobacum were highly abundant in FA12 by 16S rRNA gene sequencing. In the process of long-term acclimation with distiller's grains as a medium, the biomass of FA12 remained stable, and the pH value of fermentation liquid was also relatively stable. Meanwhile, the activities of cellulase, xylanase, and feruloyl esterase secreted by FA12 were stable in the ranges of 0.2350-0.4470, 0.1917-0.3078, and 0.1103-0.1595 U/mL, respectively, and the release of FA could reach 133.77 µg/g. It is proven that the microbial consortium has good genetic stability. In addition, the structural changes of lignocellulose in distiller's grains before and after fermentation were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR), and the changes of distiller's grains weight and lignocellulose content before and after fermentation were also detected. These results all confirmed that FA12 had the function of degrading distiller's grains. In this study, we explored a method to use microbial communities to release FA from distiller's grains and degrade lignocellulose in the waste, which opened up a new way for the application of the high value of lost waste.

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