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1.
J Cell Physiol ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943193

RESUMO

Recently, long noncoding RNA SNHG12 has been reported to be dysregulated in various types of cancer. This study investigated its biological function and the underlying molecular mechanism in cervical squamous cell carcinoma (CSCC). We found that SNHG12 was significantly overexpressed in CSCC tissues. Further evidence showed that human papillomavirus (HPV) type 16 E6 and E7 might regulate the expression level of SNHG12 by modulating transcription factor c-Myc. Functional experiments suggested that SNHG12 knockdown dramatically repressed CSCC cells proliferation, migration, and invasion while induced apoptosis in vitro as well as suppressed tumor growth in vivo. In addition, SNHG12 could facilitate epithelial-mesenchymal transition through ERK/Slug/E-cadherin pathway at least in part. Our findings highlight SNHG12 functions as an oncogenic long noncoding RNA in malignant phenotype and tumorigenesis of CSCC, which implicate it may be a potential target for CSCC treatment.

2.
Cells ; 8(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795159

RESUMO

The phytohormone jasmonic acid (JA) plays an important role in various plant developmental processes and environmental adaptations. The JA signaling pathway has been well-elucidated in the reference plant Arabidopsis thaliana. It starts with the perception of the active JA derivative, jasmonoyl-isoleucine (JA-Ile), by the F-box protein COI1 which is part of the E3-ligase SCFCOI1. Binding of JA-Ile enables the interaction between COI1 and JAZ repressor proteins. Subsequent degradation of JAZ proteins leads to the activation of transcription factors like e.g., MYC2. Here we demonstrate that the pathway can be reconstituted in transiently transformed protoplasts. Analysis of the stability of a JAZ1-fLuc fusion protein as a function of COI1 transiently expressed in coi1 protoplasts allows structure function analysis of both JAZs and COI1. Using this system, we found that conserved cysteines in COI1 influence steady state COI1 protein levels. Using a luciferase reporter gene under the control of the JAZ1 promoter enable to address those features of JAZ1 that are required for MYC2 repression. Interestingly, the conserved TIFY-motif previously described to interact with NINJA to recruit the corepressor TOPLESS is not necessary for repression. This result is in favor of the alternative repression mode that proposes a direct competition between repressive JAZs and promotive MEDIATOR25 at MYC2. Finally, using protoplasts from the aos coi1 double mutant, which is deficient in JA synthesis and perception, we provide a system that has the potential to study the activity of different COI1 variants in the presence of different ligands.

3.
Metabolism ; 101: 153998, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31666193

RESUMO

BACKGROUND: The incidence of growth hormone deficiency (GHD) in adamantinomatous craniopharyngioma (aCP) is significantly higher than in other sellar region tumors, but the possible mechanism is still elusive. A high level of inflammatory responses is another feature of aCP. We investigated the internal connection between interleukin-1α (IL-1α) and GHD, while focusing on its biological activities in pituitary fibrosis. MATERIALS AND METHODS: To diagnosis of GHD, the Body Mass Index (BMI), Insulin Like Growth Factor-1(IGF-1) and peak growth hormone (GH) values after insulin stimulation test of 15 aCP patients were recorded. Histological staining was performed on the aCP samples. Levels of 9 proinflammatory cytokines in tumor tissue and cell supernatant were detected using Millipore bead arrays. The effect of IL-1α on GH secretion was evaluated in vivo and in vitro. Western blot, qRT-PCR and cell functional assays were used to explore the potential mechanism through which IL-1α acts on GH secretion. The stereotactic ALZET osmotic pump technique was used to simulate aCP secretion of proinflammatory cytokines in rats. Recombinant IL-1α (rrIL-1α) and conditioned media (CM) prepared from the supernatant of aCP cells was infused directly into the intra-sellar at a rate of 1 µl/h over 28 days, and then the effects of IL-1α treatment on pathological changes of pituitary gland and GH secretion were measured. To further confirm whether IL-1α affects GH secretion through IL-1R1, an IL-1R1 blocker (IL-1R1a, 10 mg/kg body weight, once daily) was administered subcutaneously from the first day until day 28. RESULTS: There was a significant positive correlation between pituitary fibrosis and GHD (rS = 0.756, P = 0.001). A number of cytokines, in particular IL-1α, interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1), were elevated in tumor tissue and cell supernatant. Only IL-1α showed a significant difference between the GHD group and the No-GHD group (P < 0.001, F = 6.251 in tumor tissue; P = 0.003, F = 1.529 in cell supernatant). IL-1α significantly reduced GH secretion in coculture of GH3 and pericytes. The activation of pericytes induced by IL-1α was mediated by the IL-1R1 signaling pathway. In vivo, IL-1α induces pituitary fibrosis, further leading to a decreased level of GH. This pathological change was antagonized by IL-1R1a. CONCLUSION: This study found that the cross talk between aCP cells and stroma cells in the pituitary, i.e. pericytes, is an essential factor in the formation of GHD, and we propose that neutralization of IL-1α signaling might be a potential therapy for GHD in aCP.

4.
Xenobiotica ; : 1-8, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31609652

RESUMO

This study was to explore the effects of sulfotanshinone sodium injection (SSI) on the pharmacokinetics and pharmacodynamics of warfarin in rats. The studies of single dose and multiple dose of warfarin were designed to assess the interaction between warfarin and SSI. Rats were divided into different groups randomly and administered with warfarin in the absence or presence of SSI. Prothrombin time (PT) and activated partial thromboplastin time (APTT) values were detected by blood coagulation analyzer, and international normalized ratio (INR) values were calculated. Plasma concentrations of warfarin enantiomers were determined by UPLC-MS/MS method, pharmacokinetic parameters were calculated. The single-dose study demonstrated that the repeated doses of SSI alone had no effect on PT, APTT and INR values, but had a significant effect on PT and INR values produced by a single dose of warfarin, APTT values were unaffected. The Cmax, AUC of R-warfarin and S-warfarin were reduced, t1/2 were shortened. The multiple-dose study showed that PT, APTT, INR values, and the Cmax and AUC of R-warfarin and S-warfarin decreased significantly after administration of SSI. The finding implied that SSI could accelerate warfarin metabolism and weaken its anticoagulation. However, human SSI-warfarin interaction studies need to be conducted to confirm this finding.

5.
Medicine (Baltimore) ; 98(39): e17180, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574824

RESUMO

BACKGROUND: ATPase family, AAA+ domain containing 2 (ATAD2) is also known as AAA+ nuclear coregulator cancer-associated protein or PRO2000. ATAD2 has been reported as a prognostic factor in different cancer types, but the association between ATAD2 high expression and survival is still unclear. Thereby, this meta-analysis was performed to evaluate the prognostic value of ATAD2 high expression in human cancers. METHODS: All of the studies included were retrieved from PubMed, EMBASE, and Cochrane Library electronic databases. The clinical outcomes were evaluated by calculating hazard ratio (HR) with their 95% confidence interval (CI). RESULTS: Thirteen studies including 2689 patients were eligible for this analysis. The pooled results showed that ATAD2 over-expression was significantly associated with shorter overall survival (OS) (HR = 2.32, 95% CI = 1.77-3.02), as well as shorter recurrence-free survival (RFS), disease-free survival (DFS), and disease-specific survival (DSS) (HR = 1.83, 95% CI = 1.51-2.23) among human cancers. Subgroup analyses for OS were implemented in terms of region, tumor type, and sample size and the results were coincident with overall pooled results. Begg funnel plot and Egger test showed the presence of publication bias for OS. Sensitivity analysis indicated that both results were not affected for removing any study. CONCLUSION: ATAD2 would be likely to act as a prognostic biomarker for the patients of different cancer types and provide a guide on clinical treatment. Prospective clinical studies are needed to support these findings.


Assuntos
ATPases Associadas a Diversas Atividades Celulares/análise , Adenosina Trifosfatases/análise , Proteínas de Ligação a DNA/análise , Neoplasias/enzimologia , Neoplasias/mortalidade , Intervalo Livre de Doença , Humanos , Prognóstico , Modelos de Riscos Proporcionais
6.
Medicine (Baltimore) ; 98(37): e16974, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517816

RESUMO

BACKGROUND: Growing evidence showed that high pretreatment plasma fibrinogen could be used as a potential prognostic marker in colorectal cancer (CRC). However, the conclusions were controversial. Therefore, this meta-analysis was conducted to evaluate the prognostic value of pretreatment plasma fibrinogen in patients with CRC. METHODS: Relevant studies were searched in the databases including PubMed, EMBASE, Web of Science, Cochrane library, and China National Knowledge Infrastructure up until December 10th, 2018. Pooled hazard ratios (HRs) with their 95% confidence intervals (CIs) were used to estimate the effects. RESULTS: A total of 17 articles with 6863 patients were included in this meta-analysis. The results revealed that elevated pretreatment plasma fibrinogen was significantly associated with both poor overall survival (univariate analysis: HR = 1.69, 95% CI 1.47-1.95, P = .000; multivariate analysis: HR = 1.50, 95% CI 1.28-1.77, P = .000) and poor disease-free survival (univariate analysis: HR = 1.90, 95% CI 1.49-2.41, P = .000; multivariate analysis: HR = 2.08, 95% CI 1.52-2.86, P = .000) in patients with CRC. CONCLUSIONS: High pretreatment plasma fibrinogen level is significantly associated with worse survival outcomes in CRC patients. Plasma fibrinogen may be used as an effective prognostic marker and potential therapeutic target. Further studies are required to support these results.


Assuntos
Neoplasias Colorretais/sangue , Fibrinogênio/análise , Biomarcadores/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Humanos , Prognóstico
7.
ACS Appl Mater Interfaces ; 11(39): 35622-35629, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31502436

RESUMO

The accurate and early detection of Mycobacterium tuberculosis (Mtb) is of great significance for the clinical diagnosis and treatment of tuberculosis. In this work, we report a facile method for the controllable synthesis of a novel few-layered two-dimensional graphdiyne nanosheet (GDY NS) with a thickness of only ∼0.9 nm via an electrochemical lithium-intercalation strategy, which possesses a prominent fluorescence quenching effect. The few-layered GDY NS with its strong adsorptivity for single-stranded DNA is first proposed as a new fluorescent sensing platform for the real-time detection of DNA with excellent specificity, multiplicity, and superhigh sensitivity (limit of detection as low as 25 pM). This sensing platform can be further applied for the Mtb detection from clinical samples and the identification of drug-resistant mutants with a low background and a high signal-to-noise ratio. Herein, we provide a potential basis for the clinical development of rapid, sensitive, and accurate substitutes for the molecular diagnosis of Mtb and its drug-resistant genes.

8.
Transgenic Res ; 28(5-6): 561-572, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31435821

RESUMO

Genetic transformation of plants offers the possibility of functional characterization of individual genes and the improvement of plant traits. Development of novel transformation vectors is essential to improve plant genetic transformation technologies for various applications. Here, we present the development of a Gateway-compatible two-component expression vector system for Agrobacterium-mediated plant transformation. The expression system contains two independent plasmid vector sets, the activator vector and the reporter vector, based on the concept of the GAL4/UAS trans-activation system. The activator vector expresses a modified GAL4 protein (GAL4-VP16) under the control of specific promoter. The GAL4-VP16 protein targets the UAS in the reporter vector and subsequently activates reporter gene expression. Both the activator and reporter vectors contain the Gateway recombination cassette, which can be rapidly and efficiently replaced by any specific promoter and reporter gene of interest, to facilitate gene cloning procedures. The efficiency of the activator-reporter expression system has been assessed using agroinfiltration mediated transient expression assay in Nicotiana benthamiana and stable transgenic expression in Arabidopsis thaliana. The reporter genes were highly expressed with precise tissue-specific and subcellular localization. This Gateway-compatible two-component expression vector system will be a useful tool for advancing plant gene engineering.

9.
Immunopharmacol Immunotoxicol ; 41(4): 485-489, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31232124

RESUMO

Objective: Rapamycin has a protective cardiovascular effect and inhibits proliferation and migration of vascular smooth muscle cells. We investigated the effects of rapamycin on proliferation of cultured human umbilical arterial smooth muscle cells (HUASMCs) by determining interleukin-6 (IL-6) levels. Materials and methods: Adherent third-generation primary-cultured HUASMCs were used in the study, and MTT assay was used to measure the effects of different rapamycin concentrations on cell proliferation at various time points (3-96 h). RT-PCR was used to measure IL-6 mRNA expression and ELISA was used to measure IL-6 protein expression. Results: After three passages, HUASMCs displayed >90% confluence. Inhibition of cell proliferation by rapamycin was both time and dose dependent. When the action concentration of rapamycin was 100 ng·mL-1, the inhibitory effect was strongest after 48 h (30.25 ± 2.40)%, and the follow-up study was conducted after 48 h. When the action time of rapamycin was 48 h, the inhibitory effect of 150 ng·mL-1 at the action concentration was the strongest, and the inhibitory rate was (42.88 ± 3.84)%. There was no significant difference between the inhibitory effect and the action concentration of 100 ng·mL-1 (p>.05). Moreover, low (2 ng·mL-1), moderate (10 ng·mL-1), and high (100 ng·mL-1) rapamycin concentrations down-regulated both IL-6 mRNA and expression factor in a dose-dependent manner. Discussion and conclusions: Rapamycin inhibits proliferation of HUASMCs in vitro and through down-regulation of IL-6 expression.


Assuntos
Proliferação de Células/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Sirolimo/farmacologia , Artérias Umbilicais/efeitos dos fármacos , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Seguimentos , Humanos , Interleucina-6/metabolismo , RNA Mensageiro/metabolismo , Artérias Umbilicais/metabolismo
10.
Int J Mol Sci ; 20(12)2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31212892

RESUMO

Plant cells are separated by cellulose cell walls that impede direct cell-to-cell contact. In order to facilitate intercellular communication, plant cells develop unique cell-wall-spanning structures termed plasmodesmata (PD). PD are membranous channels that link the cytoplasm, plasma membranes, and endoplasmic reticulum of adjacent cells to provide cytoplasmic and membrane continuity for molecular trafficking. PD play important roles for the development and physiology of all plants. The structure and function of PD in the plant cell walls are highly dynamic and tightly regulated. Despite their importance, plasmodesmata are among the few plant cell organelles that remain poorly understood. The molecular properties of PD seem largely elusive or speculative. In this review, we firstly describe the general PD structure and its protein composition. We then discuss the recent progress in identification and characterization of PD-associated plant cell-wall proteins that regulate PD function, with particular emphasis on callose metabolizing and binding proteins, and protein kinases targeted to and around PD.


Assuntos
Parede Celular/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Células Vegetais/metabolismo , Plasmodesmos/metabolismo , Citoplasma/metabolismo , Glucanos/metabolismo , Glucosiltransferases/metabolismo , Relação Estrutura-Atividade
11.
Exp Neurol ; 320: 112965, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31132364

RESUMO

Leucine-rich repeat and immunoglobulin domain-containing protein 1 (LINGO-1) is a transmembrane protein that negatively regulates neural regeneration in the central nervous system. LINGO-1 expression is up-regulated after central nerve injury, and is accompanied by cell death. Both LINGO-1 and cell death in the injury microenvironment are thought to limit neural regeneration, but the relationship between LINGO-1 and cell death has not been characterized. To investigate whether LINGO-1 deletion improves the spinal cord microenvironment after spinal cord injury (SCI) and contributes to cell survival, we generated LINGO-1 knockout (KO) mice. These mice and wild-type control mice were subjected to spinal cord transection. Fourteen days after spinal cord transection, cell apoptosis, inflammation, glial scar, and growth of nerve fibers were evaluated by immunostaining. The results showed that LINGO-1 KO mice demonstrated a profound reduction in expression of caspase-3, transferase-mediated deoxyuridine triphosphate biotin nick end labeling (TUNEL), ionized calcium binding adapter molecule 1 (IBA1), glial fibrillary acidic protein (GFAP), and chondroitin sulfate proteoglycans (CSPGs) compared to controls. In contrast, expression of neurofilament (NF) at the SCI site in LINGO-1 KO mice was markedly increased compared to that in wild-type mice. These results suggested that LINGO-1 plays a critical role in the injury microenvironment in processes such as cell death, inflammatory response, and glial scar formation. Importantly, LINGO-1 deletion and a positive microenvironment may exert synergistic effects to promote nerve fiber regeneration. Therefore, inhibition of LINGO-1 may be a therapeutic strategy to promote neural regeneration following SCI.

12.
Ann Transl Med ; 7(3): 51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30906755

RESUMO

The cutaneous symptom of the paraneoplastic erythroderma can be the only symptom of a malignancy. Although many cases associated with malignancies have been reported, the pathogenesis of cancer related erythroderma is still unclear. Herein we presented a patient with large cell neuroendocrine carcinoma (LCNEC) of the lung and contemporary severe erythroderma. The patient suffered from skin erythema and scaling all over the body and the cutaneous lesions recovered completely after 3 weeks of surgery. Strong expression of neuron-specific enolase (NSE, 2+ positive) was found in both primary cancer and basal cells of the preoperative skin. Three months later, postoperative skin biopsy presented nearly normal skin tissues, accompanied with a negative expression of NSE. Nine months after surgery, cancer recurred in the liver and brain with the first symptom of skin erythema and scaling. The pathology of liver biopsy tissues illustrated the LCNEC and 3+ positive expression of NSE. The skin biopsy tissues showed 2+ positive stain of NSE. Evaluation after two cycles of chemotherapy showed marked improvement in erythroderma and reduction of tumor volume. However, the patient experienced recurrent worsening of erythroderma when chemotherapy was terminated due to severe myelosuppression. Eleven months after surgery, the patient died of cancer cachexia and multiple organ failure. To our knowledge, this was the first case of paraneoplastic erythroderma associated with LCNEC of lung. Furthermore, we firstly discovered that the deposition of NSE in basal cells might be a crucial pathogenic factor of erythroderma.

13.
ISA Trans ; 92: 257-272, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30876758

RESUMO

Integration of renewable energy (RE) sources, such as wind energy and photo voltaic (PV) energy, to a power network (grid) is usually achieved through an intermediate power electronic inverter. Ideally, the inverter is not expected to inject any form of DC component into the grid. However, this is not the case in practice as DC component are invariably generated and, subsequently, injected into the grid by the power converter, impacting on the overall power quality. To mitigate this problem, the International Grid Certification stipulates the maximum extent of DC component that can be injected into the grid current. Thus, various techniques have been proposed to maintain the DC component within the stipulated limit, however these techniques have the drawbacks of complicated control algorithm, extra power losses, and increased high costs. To solve these problems, this paper proposes a virtual-capacitor based DC current suppression control technique for grid-connected inverters, which has the advantages of fast implementation and good DC component suppression performance in utility. An LCL filter interfaced 3-phase inverter is used and virtual capacitors are incorporated into the inverter which connects the inverter with the grid. The allowable region and design methods of the inverter controller parameters which are combined with the active damping and grid voltage feedforward strategies are described in detail. Furthermore, both simulation and experimental results show that the DC component can be successfully mitigated and could satisfy the International Grid Certification standards.

14.
Medicine (Baltimore) ; 98(7): e14295, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30762728

RESUMO

RATIONALE: Hyponatremia is one of the most common electrolyte disorders in clinic. Due to the complicated etiology and the nonspecific clinical manifestations, the diagnosis of hyponatremia is a complicated process. A variety of clinical disorders can cause inappropriately increased antidiuretic hormone (ADH) secretion, leading to inappropriate water retention and consequent hyponatremia. The most common cause of hyponatremia in hospital inpatients is syndrome of inappropriate antidiuretic (SIADH). The action of glucocorticoid against pituitary posterior lobe can reduce the secretion of ADH. However, the effect of hormone on diuretic hormone during treatment has been less reported. PATIENT CONCERNS AND DIAGNOSIS: The patient in this case report was misdiagnosed as anterior pituitary hypofunction because of the long-term glucocorticoid therapy was effective in this patient, and the patient was finally diagnosed as SIADH after reassessment. The patient is a 76-year-old male with long-term symptomatic hyponatremia after traumatic brain injury (TBI). The patient has been consistently diagnosed as anterior pituitary hypofunction. Based on the diagnosis, glucocorticoid replacement therapy was administered. The serum sodium of the patient gradually increased to normal level after hydrocortisone intravenous injection but dropped again after switch to hydrocortisone oral administration. Through examination and analysis of the patient status during the five-time hospitalization, syndrome of inappropriate antidiuretic hormone (SIADH) was considered. INTERVENTIONS: Water intake limitation and oral furosemide and antisterone were administered after glucocorticoid therapy was stopped. OUTCOME: The serum sodium level of the patient gradually increased and maintained within normal range based on his clinical follow-up. LESSONS: For hyponatremia with effective glucocorticoid treatment, SIADH should still be excluded.


Assuntos
Glucocorticoides/efeitos adversos , Hiponatremia/etiologia , Hipopituitarismo/diagnóstico , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/diagnóstico , Idoso , Lesões Encefálicas Traumáticas/complicações , Erros de Diagnóstico , Glucocorticoides/uso terapêutico , Humanos , Hipopituitarismo/tratamento farmacológico , Masculino
15.
Int J Mol Sci ; 20(3)2019 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-30720746

RESUMO

During their lifetime, plants encounter numerous biotic and abiotic stresses with diverse modes of attack. Phytohormones, including salicylic acid (SA), ethylene (ET), jasmonate (JA), abscisic acid (ABA), auxin (AUX), brassinosteroid (BR), gibberellic acid (GA), cytokinin (CK) and the recently identified strigolactones (SLs), orchestrate effective defense responses by activating defense gene expression. Genetic analysis of the model plant Arabidopsis thaliana has advanced our understanding of the function of these hormones. The SA- and ET/JA-mediated signaling pathways were thought to be the backbone of plant immune responses against biotic invaders, whereas ABA, auxin, BR, GA, CK and SL were considered to be involved in the plant immune response through modulating the SA-ET/JA signaling pathways. In general, the SA-mediated defense response plays a central role in local and systemic-acquired resistance (SAR) against biotrophic pathogens, such as Pseudomonas syringae, which colonize between the host cells by producing nutrient-absorbing structures while keeping the host alive. The ET/JA-mediated response contributes to the defense against necrotrophic pathogens, such as Botrytis cinerea, which invade and kill hosts to extract their nutrients. Increasing evidence indicates that the SA- and ET/JA-mediated defense response pathways are mutually antagonistic.


Assuntos
Arabidopsis/metabolismo , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Salicílico/metabolismo , Transdução de Sinais , Arabidopsis/genética , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Reguladores de Crescimento de Planta/metabolismo , Pseudomonas syringae
17.
J Am Chem Soc ; 141(4): 1583-1592, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30645104

RESUMO

The structural principles that govern interactions between l- and d-peptides are not well understood. Among natural proteins, coiled-coil assemblies formed between or among α-helices are the most regular feature of tertiary and quaternary structures. We recently reported the first high-resolution structures for heterochiral coiled-coil dimers, which represent a starting point for understanding associations of l- and d-polypeptides. These structures were an unexpected outcome from crystallization of a racemic peptide corresponding to the transmembrane domain of the influenza A M2 protein (M2-TM). The reported structures raised the possibility that heterochiral coiled-coil dimers prefer an 11-residue (hendecad) sequence repeat, in contrast to the 7-residue (heptad) sequence repeat that is dominant among natural coiled coils. To gain insight on sequence repeat preferences of heterochiral coiled-coils, we have examined three M2-TM variants containing substitutions intended to minimize steric clashes between side chains at the coiled-coil interface. In each of the three new crystal structures, we observed heterochiral coiled-coil associations that closely match a hendecad sequence motif, which strengthens the conclusion that this motif is intrinsic to the pairing of α-helices with opposite handedness. In each case, the presence of a hendecad motif was established by comparing the observed helical frequency to that of an ideal hendecad. This comparison revealed that decreasing the size of the amino acid side chain at positions that project toward the superhelical axis produces tighter packing, as determined by the size of the coiled-coil radius. These results provide a basis for future design of heterochiral coiled-coil pairings.

18.
Ann Thorac Surg ; 107(3): 921-928, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30403979

RESUMO

BACKGROUND: The purpose of this study is to use 3-dimensional printing (3DP) polyetheretherketone (PEEK) implants for skeletal reconstructions after wide excision of chest wall. 3DP PEEK implants were expected to provide a better physiological simulation than traditional ones because of a closer elastic modulus to cortical bone and similar biomechanical properties. METHODS: Eighteen patients (mean age 44.5 years), comprising 6 males and 12 females, underwent adequate radical wide excision for tumors and chest wall reconstruction using 3DP PEEK implants. Surgical data, which include patient demographic characteristics, implant preparation parameters, and preoperative and postoperative pulmonary function test results, were collected and analyzed. RESULTS: Ten patients with rib tumors and 8 patients with sternum tumors were selected for the study. The mean chest wall defect size was 173.6 ± 151.5 cm2 (range, 55 to 625 cm2). The mean weight of a single 3DP PEEK rib and sternum was 28 g and 104 g, respectively. The flexural and tensile strength of PEEK implants were 141 ± 7 MPa and 89 ± 3 MPa, respectively. Preoperative and postoperative pulmonary function tests revealed that mean forced vital capacity was from 2.79 ± 0.68 L to 2.40 ± 0.70 L with a reduction of 14.0% (p < 0.001). No side effects were observed 6 to 12 months after the operation. CONCLUSIONS: These findings suggest that 3DP PEEK implant is a safe and effective alternative in the reconstruction of chest wall defects. The pulmonary function of the patient may be preserved effectively after surgery.


Assuntos
Cetonas , Polietilenoglicóis , Impressão Tridimensional , Neoplasias Torácicas/cirurgia , Parede Torácica/cirurgia , Toracoplastia/métodos , Adolescente , Adulto , Idoso , Materiais Biocompatíveis , Projeto Auxiliado por Computador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Tomografia por Emissão de Pósitrons , Desenho de Prótese , Estudos Retrospectivos , Neoplasias Torácicas/diagnóstico , Parede Torácica/diagnóstico por imagem , Adulto Jovem
19.
New Phytol ; 221(4): 1906-1918, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30252136

RESUMO

TGACG-BINDING FACTORs (TGAs) control the developmental or defense-related processes. In Arabidopsis thaliana, the functions of at least TGA2 and PERIANTHIA (PAN) can be repressed by interacting with CC-type glutaredoxins, which have the potential to control the redox state of target proteins. As TGA1 can be redox modulated in planta, we analyzed whether some of the 21 CC-type glutaredoxins (ROXYs) encoded in the Arabidopsis genome can influence TGA1 activity in planta and whether the redox active cysteines of TGA1 are functionally important. We show that the tga1 tga4 mutant and plants ectopically expressing ROXY8 or ROXY9 are impaired in hyponastic growth. As expression of ROXY8 and ROXY9 is activated upon transfer of plants from hyponasty-inducing low light to normal light, they might interfere with the growth-promoting function of TGA1/TGA4 to facilitate reversal of hyponastic growth. The redox-sensitive cysteines of TGA1 are not required for induction or reversal of hyponastic growth. TGA1 and TGA4 interact with ROXYs 8, 9, 18, and 19/GRX480, but ectopically expressed ROXY18 and ROXY19/GRX480 do not interfere with hyponastic growth. Our results therefore demonstrate functional specificities of individual ROXYs for distinct TGAs despite promiscuous protein-protein interactions and point to different repression mechanisms, depending on the TGA/ROXY combination.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Glutarredoxinas/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/genética , Domínio Catalítico , Cisteína/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Genes de Plantas , Glutarredoxinas/genética , Luz , Modelos Biológicos , Mutação/genética , Plantas Geneticamente Modificadas , Protoplastos/efeitos dos fármacos , Protoplastos/metabolismo , Protoplastos/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ácido Salicílico/farmacologia , Transcrição Genética/efeitos dos fármacos , Transcrição Genética/efeitos da radiação , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Transcriptoma/efeitos da radiação
20.
ISA Trans ; 88: 268-279, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30554893

RESUMO

Due to the scaling and zero-drift of current sensor errors, unbalanced grid voltages, tolerance of power switching devices, and asymmetry of PWM gate driving pulses, transformerless grid-connected inverters usually have certain amount of dc components injected to the ac grid. Therefore, power quality of the grid is degraded. Many efforts, such as using blocking capacitors, a dc current feedback control method, and a voltage dc component feedback control method, etc., have been introduced to minimize the dc injection. This paper proposes an intelligent control strategy of dc current injection suppression to the grid by utilizing adaptive-back-propagation (ABP) neural network PID controller. The performance of the proposed scheme is evaluated and compared with the traditional and existing method. Finally, the control scheme is verified on a 2-kW three-phase grid-connected inverter in the laboratory.

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