Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 48
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Sleep Res ; : e13046, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293774

RESUMO

There is now increasing evidence demonstrating that obstructive sleep apnea (OSA) contributes to microvascular disorder. However, whether OSA is associated with impaired coronary flow reserve is still unclear. Therefore, we conducted this systematic review and meta-analysis to summarize current evidence. In a systematic review, PubMed, Embase, the Cochrane Library and Web of Science were searched; five observational studies fulfilled the selection criteria and were included in this study. Data were extracted from selected studies and meta-analysis was performed using random-effects modelling. In all, 829 OSA patients and 507 non-OSA subjects were included and assessed for coronary flow reserve (CFR), the clinical indicator of coronary microvascular dysfunction (CMD). For all studies, OSA was significantly associated with reduced CFR. The pooled weighted mean difference (WMD) of CFR was -0.78 (95% confidence interval [CI] -1.25 to -0.32, p ï¼œ 0.001, I2  = 84.4%). The difference in the apnea-hypopnea index (AHI) between studies can explain 89% of heterogeneity (coef = -0.05, 95% CI -0.12 to 0.02, p = .078) in a meta-regression, indicating the CFR tended to negatively correlate with severity of OSA. The Egger regression test did not show statistical significance (p = .49). In conclusion, there are plausible biological mechanisms linking OSA and CMD, and the preponderance of evidence from this systematic review suggests that OSA, especially severe OSA, is associated with reduced CFR. Future studies are warranted to further delineate the exact role of OSA in CMD occurrence and development in a prospective setting.

2.
Appl Radiat Isot ; 159: 109061, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32068147

RESUMO

Combining the SCE algorithm (Shuffled Complex Evolution), MOEA/D algorithm (Multi-Objective Evolutionary Algorithm based on Decomposition), MCNP program and several prediction models, two multi-objective optimization methods (priori method and posteriori method) for radiation shielding material, which considering the shielding, mass, volume, mechanical and thermal properties are established. The material is in the form of resin matrix composite. The shielding performance of the material is simulated by MCNP program. The mechanical property and thermal property are calculated by some widely used prediction models. Several materials are optimized by the two methods respectively, and comparisons among the materials are made. The results show that, both the two methods could achieve synergistic optimization of shielding, mass, volume, mechanical properties and thermal properties of material. Differently, the priori method only obtains one solution corresponding to its weight values, while the posteriori method obtains the whole Pareto-optimal set. These two methods have their own advantages and disadvantages, which should be selected according to the actual situation.

3.
Mol Genet Genomic Med ; 8(1): e1063, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31793236

RESUMO

BACKGROUND: Methylmalonic acidemia (MMA) is an autosomal recessive genetic disorder involving the metabolism of organic acids. METHODS: Here, we report the case of a patient who developed acute metabolic crisis after vaccination and was diagnosed with cblA type MMA after hospitalization. RESULTS: Further examination revealed a homozygous pathogenic variant in the MMAA gene that caused the disease in the patient but did not conform to Mendelian inheritance. Using chromosomal microarray analysis, maternal uniparental disomy (UPD) was found on chromosome 4q26-q35.2 of the patient. The MMAA gene of the patient was inherited only from the mother and carried the same pathogenic variant on both alleles of chromosome 4. MMAA gene expression levels in whole blood were detected by real-time PCR. CONCLUSION: The nonsense pathogenic variant, NM_172250.2:c.742C>T (p.Gln248*), carried by the patient leads to a premature termination of transcription of the gene, thereby resulting in partial loss of protein function while retaining some others. Segmental UPD 4 is rare, and to our knowledge, has not been reported previously.

4.
Biosci Biotechnol Biochem ; 84(1): 111-117, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31512553

RESUMO

Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial-mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson's analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments.


Assuntos
Adenocarcinoma/patologia , Movimento Celular , Proliferação de Células , Neoplasias do Colo/patologia , Transição Epitelial-Mesenquimal , Troponina T/genética , Troponina T/metabolismo , Antígenos CD/metabolismo , Caderinas/metabolismo , Bases de Dados Genéticas , Expressão Gênica , Técnicas de Silenciamento de Genes , Células HCT116 , Humanos , Invasividade Neoplásica , Prognóstico , Transfecção
5.
Horm Metab Res ; 51(11): 729-734, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31683343

RESUMO

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

6.
Proc Natl Acad Sci U S A ; 116(47): 23404-23409, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685626

RESUMO

Phase transitions in halide perovskites triggered by external stimuli generate significantly different material properties, providing a great opportunity for broad applications. Here, we demonstrate an In-based, charge-ordered (In+/In3+) inorganic halide perovskite with the composition of Cs2In(I)In(III)Cl6 in which a pressure-driven semiconductor-to-metal phase transition exists. The single crystals, synthesized via a solid-state reaction method, crystallize in a distorted perovskite structure with space group I4/m with a = 17.2604(12) Å, c = 11.0113(16) Å if both the strong reflections and superstructures are considered. The supercell was further confirmed by rotation electron diffraction measurement. The pressure-induced semiconductor-to-metal phase transition was demonstrated by high-pressure Raman and absorbance spectroscopies and was consistent with theoretical modeling. This type of charge-ordered inorganic halide perovskite with a pressure-induced semiconductor-to-metal phase transition may inspire a range of potential applications.

7.
PLoS Genet ; 15(10): e1008474, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658266

RESUMO

Circadian clocks control daily rhythms in behavior and physiology. In Drosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons generating locomotor rhythms. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify the Drosophila SWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM in circadian neurons eliminates morning anticipatory activity under light dark cycle and impairs behavioral rhythmicity in constant darkness. Interestingly, the two major splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion mainly leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period without affecting the circadian rhythmicity. Both DOM-A and DOM-B bind to the promoter regions of key pacemaker genes period and timeless, and regulate their protein expression. However, we identify that only DOM-A is required for the maintenance of sLNvs and transcription of pdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that two splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance.


Assuntos
Relógios Biológicos/genética , Ritmo Circadiano/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiologia , Fatores de Transcrição/genética , Núcleos Ventrais do Tálamo/fisiologia , Processamento Alternativo , Animais , Animais Geneticamente Modificados , Técnicas de Observação do Comportamento , Comportamento Animal , Proteínas de Drosophila/metabolismo , Feminino , Masculino , Neurônios/metabolismo , Neuropeptídeos/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Transcrição/metabolismo , Núcleos Ventrais do Tálamo/citologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-31227860

RESUMO

Previously, two studies have provided evidence that bats can use magnetic field cues for homing or roosting. For insectivorous bats, it is well established that foraging represents one of the most fundamental behaviors in animals relies on their ability to echolocate. Whether echolocating bats can also use magnetic cues during foraging remains unknown, however. Here, we tested the orientation behavior of Chinese noctules (Nyctalus plancyi) during foraging in a plus-shaped, 4-channel apparatus under different magnetic field conditions. To minimize the effects of spatial memory on orientation from repeated experiments, naïve bats were tested only once in each experimental condition. As expected, under geomagnetic field and a food resource offered conditions, the bats significantly preferred to enter the channel containing food, indicating that they primarily relied on direct sensory signals unrelated to magnetic cues. In contrast, when we offered food simultaneously in all four channels and minimized any differences in all other sensory signals available, the bats exhibited a clear directional preference to forage along the magnetic field direction under either geomagnetic field or a magnetic field in which the horizontal component was rotated by 90°. Our study offers a novel evidence for the importance of a geomagnetic field during foraging.

9.
Theranostics ; 9(11): 3341-3364, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244957

RESUMO

Major objectives in nanomedicine and nanotherapy include the ability to trap therapeutic molecules inside of nano-carriers, carry therapeutics to the site of the disease with no leakage, release high local concentrations of drug, release only on demand - either autonomous or external, and kill the cancer cells or an infectious organism. This review will focus on mesoporous silica nanoparticle carriers (MSN) with a large internal pore volume suitable for carrying anticancer and antibiotic drugs, and supramolecular components that function as caps that can both trap and release the drugs on-command. Caps that are especially relevant to this review are rotaxanes and pseudorotaxanes that consist of a long chain-like molecule threaded through a cyclic molecule. Under certain conditions discussed throughout this review, the cyclic molecule can be attracted to one end of the rotaxane and in the presence of a stimulus can slide to the other end. When the thread is attached near the pore opening on MSNs, the sliding cyclic molecule can block the pore when it is near the particle or open it when it slides away. The design, synthesis and operation of supramolecular systems that act as stimuli-responsive pore capping devices that trap and release molecules for therapeutic or imaging applications are discussed. Uncapping can either be irreversible because the cap comes off, or reversible when the cyclic molecule is prevented from sliding off by a steric barrier. In the latter case the amount of cargo released (the dose) can be controlled. These nanomachines act as valves. Examples of supramolecular systems stimulated by chemical signals (pH, redox, enzymes, antibodies) or by external physical signals (light, heat, magnetism, ultrasound) are presented. Many of the systems have been studied in vitro proving that they are taken up by cancer cells and release drugs and kill the cells when stimulated. Some have been studied in mouse models; after IV injection they shrink tumors or kill intracellular pathogens after stimulation. Supramolecular constructs offer fascinating, highly controllable and biologically compatible platforms for drug delivery.

10.
EBioMedicine ; 44: 71-85, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31129099

RESUMO

BACKGROUND: Increased frequency of CCR9+ CD4+ T cells in peripheral blood is linked to several gastrointestinal inflammatory diseases; however, its relationship with necrotizing enterocolitis (NEC) is not understood. We investigated whether the frequencies of CCR9+ CD4+ T cells and related subsets were increased in peripheral blood of both patients and mice with NEC. METHODS: CCR9+ CD4+ T cells and related subsets were evaluated by flow cytometry in peripheral blood collected from both patients and mice with NEC and controls. The suppressive function of CCR9+ regulatory T (Treg) cells in NEC was assessed via in vitro suppression assay. An in vitro T cell polarization assay was performed to investigate the role of proinflammatory cytokines in Treg cell polarization. In vivo Treg cell polarization analysis was performed using NEC mice treated with anti-interleukin-6 (IL-6) receptor antibody. FINDINGS: A higher proportion of CCR9+ CD4+ T cells occurred in peripheral blood of both patients and mice with NEC than in controls. Elevated CCR9+ CD4+ T cells were primarily CCR9+ IL-17-producing Treg cells, possessing features of conventional Treg cells, but their suppressive activity was seriously impaired and negatively correlated with the severity of intestinal tissue injury. IL-6 promoted polarization of CCR9+ Treg cells to CCR9+ IL-17-producing Treg cells, and blocking IL-6 signalling inhibited this conversion in vitro and ameliorated experimental NEC in vivo. INTERPRETATION: Collectively, these data suggested that CCR9+ IL-17-producing Treg cells may be a biomarker of severity and highlight the possibility that antibodies targeting IL-6R could ameliorate NEC by modulating lymphocyte balance. FUND: This work was supported by the Science and Technology Planning Project of Guangdong Province, China (2017A020215100), the Science and Technology Foundation of Guangzhou, China (201704020086 and 201604020154), the Medical Scientific Research Foundation of Guangdong Province, China (A2017304 and A2014704), and the Social Science and Technology Development Foundation of Dongguan, China (2016108101037).


Assuntos
Enterocolite Necrosante/etiologia , Enterocolite Necrosante/metabolismo , Interleucina-17/biossíntese , Ativação Linfocitária/imunologia , Receptores CCR/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Enterocolite Necrosante/diagnóstico , Feminino , Humanos , Imunomodulação , Imunofenotipagem , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Camundongos , Células T Invariáveis Associadas à Mucosa/imunologia , Células T Invariáveis Associadas à Mucosa/metabolismo , Índice de Gravidade de Doença , Células Th17/imunologia , Células Th17/metabolismo
11.
Nanoscale ; 11(6): 2644-2654, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30575840

RESUMO

Iron oxide nanoparticles with good biocompatibility can serve as safe magnetic resonance imaging contrast agents. Herein, we report that ultrafine ferritin-based iron oxide (hematite/maghemite) nanoparticles synthesized by controlled biomimetic mineralization using genetically recombinant human H chain ferritin can be used as a positive contrast agent in magnetic resonance angiography. The synthesized magnetoferritin with an averaged core size of 2.2 ± 0.7 nm (hereafter named M-HFn-2.2) shows a r1 value of 0.86 mM-1 s-1 and a r2/r1 ratio of 25.1 at a 7 T magnetic field. Blood pool imaging on mice using the M-HFn-2.2 nanoparticles that were injected through a tail vein by single injection at a dose of 0.54 mM Fe per kg mouse body weight enabled detecting detailed vascular nets at 3 minutes post-injection; the MR signal intensity continuously enhanced up to 2 hours post-injection, which is much longer than that of the commercial magnevist (Gd-DTPA) contrast. Moreover, biodistribution examination indicates that organs such as liver, spleen and kidney safely cleared the injected nanoparticles within one day after the injection, demonstrating no risk of iron overload in test mice. Therefore, this study sheds light on developing high-performance gadolinium free positive magnetic resonance contrast agents for biomedical applications.


Assuntos
Meios de Contraste , Ferritinas , Angiografia por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Animais , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Meios de Contraste/química , Meios de Contraste/farmacocinética , Ferritinas/química , Ferritinas/farmacocinética , Humanos , Camundongos , Tamanho da Partícula , Distribuição Tecidual
12.
Can J Diabetes ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31902718

RESUMO

OBJECTIVES: Maternal diabetes mellitus (including pre-existing and gestational diabetes mellitus) is linked with adverse infant outcomes. However, the question of whether maternal diabetes increases the risk of persistent pulmonary hypertension of the newborn (PPHN) is unclear. Herein, we conducted a systematic review and meta-analysis to summarize clinical evidence to determine the association between maternal diabetes mellitus and PPHN. METHODS: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, Cochrane Library, Web of Science and Google Scholar to identify relevant studies according to predefined criteria. Data from selected studies were extracted, and meta-analysis was performed using fixed effects modelling. RESULTS: In all, we included 7 unique studies with aggregated data on 2 million individuals and >5,000 cases of PPHN. Maternal diabetes was significantly associated with a higher risk of PPHN (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.23 to 1.51). Both case-control and cohort studies exhibited that the presence of maternal diabetes increased the risk of PPHN (case-control: RR, 1.91; 95% CI, 1.02 to 2.79; cohort: RR, 1.36; 95% CI, 1.22 to 1.50). By omitting 1 study at a time, sensitivity analysis made sure that no individual study was entirely responsible for the combined results. CONCLUSIONS: Maternal diabetes was associated with increased risk of PPHN. For babies with refractory hypoxemia, with mothers with diabetes, PPHN should be taken into consideration in clinical practice.

13.
Appl Radiat Isot ; 159: 108940, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068142

RESUMO

Optimizing the shielding material via intelligent optimization algorithms has become a tendency in recent years. This study investigated the calculation modes used in the optimization. Two modes are presented in this study. Mode A optimizes the shield with a variable thickness, the result optimized is exactly the desired result. It is suitable for the application that only need material with small thickness (less than several mean free paths), such as compact systems or mobile devices. Mode B optimizes the shield with a fixed thickness, the optimized result is just an intermediate solution, and the final result needs to be extrapolated. It could be applied to optimize the material whose thickness needed is comparatively larger. Several materials were optimized using the two modes, and comparisons among the materials were made. It is found that, the material properties optimized by the two modes are basically the same, and the thickness should be set at about 10 mean free paths of neutrons in those materials when the mode B is adopted.

14.
J Neuroinflammation ; 15(1): 299, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30373627

RESUMO

BACKGROUND: Although studies have reported an increased risk for mood disorders in Hashimoto's thyroiditis (HT) patients even in the euthyroid state, the mechanisms involved remain unclear. Neuroinflammation may play a key role in the etiology of mood disorders in humans and behavioral disturbances in rodents. Therefore, this study established a euthyroid HT model in mice and investigated whether HT itself was capable of triggering neuroinflammation accompanied by emotional alterations. METHODS: Experimental HT was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Four weeks after the last challenge, mice were tested for anxiety-like behavior in the open field and elevated plus maze tests and depression-like behavior in the forced swimming and tail suspension tests. Then, animals were sacrificed for thyroid-related parameter measure as well as detection of cellular and molecular events associated with neuroinflammation. The changes in components of central serotonin signaling were also investigated. RESULTS: HT mice showed intrathyroidal monocyte infiltration and rising serum thyroid autoantibody levels accompanied by normal thyroid function, which defines euthyroid HT in humans. These mice displayed more anxiety- and depressive-like behaviors than controls. HT mice further showed microglia and astrocyte activation in the frontal cortex detected by immunohistochemistry, real-time RT-PCR, and transmission electron microscopy (TEM). These observations were also accompanied by enhanced gene expression of proinflammatory cytokines IL-1ß and TNF-α in the frontal cortex. Despite this inflammatory response, no signs of neuronal apoptosis were visible by the TUNEL staining and TEM in the frontal cortex of HT mice. Additionally, IDO1 and SERT, key serotonin-system-related genes activated by proinflammatory cytokines, were upregulated in HT mice, accompanied by reduced frontal cortex serotonin levels. CONCLUSIONS: Our results are the first to suggest that HT induces neuroinflammation and alters related serotonin signaling in the euthyroid state, which may underlie the deleterious effects of HT itself on emotional function.


Assuntos
Sintomas Afetivos/etiologia , Encefalite/etiologia , Doença de Hashimoto/complicações , Animais , Encéfalo/patologia , Encéfalo/ultraestrutura , Proteínas de Ligação ao Cálcio/metabolismo , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Encefalite/patologia , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Adjuvante de Freund/toxicidade , Proteína Glial Fibrilar Ácida/metabolismo , Doença de Hashimoto/etiologia , Doença de Hashimoto/patologia , Elevação dos Membros Posteriores , Marcação In Situ das Extremidades Cortadas , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos NOD , Proteínas dos Microfilamentos/metabolismo , Microscopia Eletrônica de Transmissão , Neuroglia/patologia , Neuroglia/ultraestrutura , Neurônios/patologia , Neurônios/ultraestrutura , Natação/psicologia
15.
Med Sci Monit ; 24: 7431-7437, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30333473

RESUMO

BACKGROUND The aim of this study was to perform gene detection in 2 clinical cases of highly suspected ornithine transcarbamylase deficiency (OTCD) pediatric patients by first-generation sequencing technology in order to confirm the pathogenic genetic factors of their families and allow the families to undergo genetic counselling and prenatal diagnosis. MATERIAL AND METHODS The peripheral DNA samples of 2 children with highly suspected OTCD (the probands) and their parents were collected. DNA fragments corresponding to exons 1-10 of the OTC gene from the samples were amplified using polymerase chain reaction (PCR), and then subjected to Sanger sequencing to confirm the pathogenic mutation sites. RESULTS The probands were both confirmed to have OTCD. The proband in Family 1 was a male carrying a c.867+1G>C mutation at a splice site within the OTC gene. The gene detection results of amniotic fluid cells at 16 weeks of pregnancy showed that the fetus was a male who also carried the c.867+1G>C mutation. The proband in Family 2 was a male carrying a c.782T>C(p. I261T) mutation in the OTC gene. The gene detection results of amniotic fluid cells at 18 weeks showed that the fetus was a male without pathogenic mutations in the OTC gene. The gene detection results of peripheral blood from the fetus after birth were consistent with those obtained from amniotic fluid cells. CONCLUSIONS Pediatric children who are clinically suspected of OTCD can receive a definitive diagnosis through OTC gene detection.


Assuntos
Doença da Deficiência de Ornitina Carbomoiltransferase/diagnóstico , Doença da Deficiência de Ornitina Carbomoiltransferase/genética , Ornitina Carbamoiltransferase/genética , Adulto , Líquido Amniótico/citologia , DNA/genética , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Ornitina Carbamoiltransferase/metabolismo , Linhagem , Reação em Cadeia da Polimerase , Gravidez , Diagnóstico Pré-Natal/métodos , Análise de Sequência de DNA
16.
Front Microbiol ; 9: 1569, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30065707

RESUMO

Magnetotactic bacteria (MTB) are a diverse group of microorganisms capable of using geomagnetic fields for navigation. This magnetotactic behavior can help microorganisms move toward favorable habitats for optimal growth and reproduction. A comprehensive understanding of the magnetotactic mechanism at molecular levels requires highly efficient genomic editing tools, which remain underdeveloped in MTB. Here, we adapted an engineered CRISPR-Cas9 system for efficient inactivation of genes in a widely used MTB model strain, Magnetospirillum magneticum AMB-1. By combining a nuclease-deficient Cas9 (dCas9) and single-guide RNA (sgRNA), a CRISPR interference system was successfully developed to repress amb0994 expression. Furthermore, we constructed an in-frame deletion mutant of amb0994 by developing a CRISPR-Cas9 system. This mutant produces normal magnetosomes; however, its response to abrupt magnetic field reversals is faster than wild-type strain. This behavioral difference is probably a consequence of altered flagella function, as suggested with our dynamics simulation study by modeling M. magneticum AMB-1 cell as an ellipsoid. These data indicate that, Amb0994 is involved in the cellular response to magnetic torque changes via controlling flagella. In summary, this study, besides contributing to a better understanding of magnetotaxis mechanism, demonstrated the CRISPR-(d)Cas9 system as a useful genetic tool for efficient genome editing in MTB.

17.
Appl Radiat Isot ; 139: 169-174, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29778764

RESUMO

To optimize the shield for neutrons and gamma rays compact and lightweight, a method combining the structure and components together was established employing genetic algorithms and MCNP code. As a typical case, the fission energy spectrum of 235U which mixed neutrons and gamma rays was adopted in this study. Six types of materials were presented and optimized by the method. Spherical geometry was adopted in the optimization after checking the geometry effect. Simulations have made to verify the reliability of the optimization method and the efficiency of the optimized materials. To compare the materials visually and conveniently, the volume and weight needed to build a shield are employed. The results showed that, the composite multilayer material has the best performance.

18.
Nanoscale ; 10(7): 3342-3349, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29387846

RESUMO

Meter-scale uniform g-CN nanorod (NR) arrays were directly grown on an FTO glass using an unprecedented vacuum magnetic filtered arc ion plating system for enhanced photoelectrochemical (PEC) performance. The construction of the g-CN film is based on the substrate deposition of the direct reaction of ionized carbon and nitrogen species, a gas-based bottom-up approach, distinctly different from the traditional powder deposition and thermal vapor pathways. The g-CN film exhibits obvious advantages over conventional ones in the application of PEC: (1) direct reaction of C and N species allows the formation of the g-CN without intralayer hydrogen bonds, which significantly reduces intralayer photogenerated charge carriers transfer resistance; (2) the g-CN exhibits the NR array structure and comprises considerably numerous layers stacking by stacking and vertically standing on the FTO substrate, which facilitates the photogenerated charges transfer and increases the contact area with electrolyte; (3) the robust mechanical strength of the g-CN NR film with the FTO substrate not only favors the effective charge transport but also allows long-term practical application against abrasion; (4) the gas-based bottom-up approach enables the g-CN to easily couple with, including but not limited to, TiO2 NR array to form heterostructures to further improve charge separation.

19.
Appl Radiat Isot ; 135: 147-154, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29413830

RESUMO

To minimize the size and weight of a vehicle-mounted accelerator-driven D-T neutron source and protect workers from unnecessary irradiation after the equipment shutdown, a method to optimize radiation shielding material aiming at compactness, lightweight, and low activation for the fast neutrons was developed. The method employed genetic algorithm, combining MCNP and ORIGEN codes. A series of composite shielding material samples were obtained by the method step by step. The volume and weight needed to build a shield (assumed as a coaxial tapered cylinder) were adopted to compare the performance of the materials visually and conveniently. The results showed that the optimized materials have excellent performance in comparison with the conventional materials. The "MCNP6-ACT" method and the "rigorous two steps" (R2S) method were used to verify the activation grade of the shield irradiated by D-T neutrons. The types of radionuclide, the energy spectrum of corresponding decay gamma source, and the variation in decay gamma dose rate were also computed.

20.
New Phytol ; 218(3): 1143-1155, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28675441

RESUMO

Programmed cell death (PCD) induced by endoplasmic reticulum (ER) stress is implicated in various plant physiological processes, yet its mechanism is still elusive. An activation of caspase-3-like enzymatic activity was clearly demonstrated but the role of the two known plant proteases with caspase-3-like activity, cathepsin B and proteasome subunit PBA1, remains to be established. Both genetic downregulation and chemical inhibition were used to investigate the function of cathepsin B and PBA1 in ER-stress-induced PCD (ERSID). Transcript level and activity labelling of cathepsin B were used to assess activation. To study tonoplast rupture, a plant PCD feature, both confocal and electronic microscopies were used. Cathepsin B downregulation reduced reactive oxygen species (ROS) accumulation and ERSID without affecting the induction of the unfolded protein response (UPR), but downregulation of PBA1 increased UPR and ERSID. Tonoplast rupture was not altered in the cathepsin B mutant and cathepsin B activation was independent of vacuolar processing enzyme (VPE). VPE activity was independent of cathepsin B. ERSID is regulated positively by cathepsin B and negatively by PBA1, revealing a complex picture behind caspase-3-like activity in plants. Cathepsin B may execute its function after tonoplast rupture and works in parallel with VPE.


Assuntos
Apoptose , Proteínas de Arabidopsis/metabolismo , Arabidopsis/citologia , Arabidopsis/enzimologia , Caspase 3/metabolismo , Catepsina B/metabolismo , Cisteína Endopeptidases/metabolismo , Estresse do Retículo Endoplasmático , Complexo de Endopeptidases do Proteassoma/metabolismo , Regulação para Baixo , Fenótipo , Plântula/metabolismo , Resposta a Proteínas não Dobradas , Vacúolos/metabolismo , Vacúolos/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA