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1.
Sci Total Environ ; 935: 173371, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772486

RESUMO

Abundant naturally and anthropogenically exposed surrounding rocks (NESRs and AESRs) in mining areas may pose persistent threats as sources of potentially toxic elements (PTEs), but this has been historically overlooked, especially for thallium (Tl) and arsenic (As). Here, the release risks of Tl and As from both NESRs and AESRs in a typical TlAs sulfide mining area were investigated. In a single leaching process, AESRs released 10.4 % of total Tl (157 µg L-1) and 32.5 % of total As (4089 µg L-1), 2-3 orders of magnitude higher than NESRs. Prolonged multiple leaching tests revealed notable and long-term risks of release of Tl and As from AESRs, associated with oxidation and dissolution of iron/sulfur-bearing minerals. Substantial release of PTEs was linked to the transformation/degradation of the -OH functional group and extensive dissolution of secondary sulfate minerals in AESRs. Ultrafiltration and STEM-EDS indicate that 18.4 % of water-extracted As released from AESRs existed as natural nanoparticles consisting of iron/sulfur-bearing minerals. This study highlights the high risks of Tl and As release from anthropogenically exposed surrounding rocks and the importance of nanoparticles in PTE transport, and provides insights into the control of PTEs in mining areas.

2.
Environ Pollut ; 346: 123704, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38442823

RESUMO

East Yunnan province in southwest China is a region with elevated natural abundance (high geological background levels) of Cd due to high metal (loid) contents in the soils. Enzyme activities are useful indicators of metal (loid) toxicity in contaminated soils and whether Cd inhibits enzyme activities in paddy soils in high geological background areas is of considerable public concern. A pot experiment combined with field investigation was conducted to assess the effects of Cd on six soil enzymes that are essential to the cycling of C, N, and P in soils. Inhibitory effects of Cd fractions on enzyme activities were assessed using ecological dose-response models. The impact of soil properties on the inhibition of sensitive soil enzymes by Cd were assessed using linear and structural equation models. Cadmium was enriched in the paddy soils with 72.2 % of soil samples from high geological background areas exceeding the Chinese threshold values (GB 15618-2018) of Cd. Enzyme responses to Cd contamination varied markedly with a negative response by catalase but a positive response by invertase. Urease, ß-glucosidase, and alkaline phosphatase activities were stimulated at low Cd concentrations and inhibited at high concentrations. The average inhibition ratios of ß-glucosidase, urease, and catalase in high Cd levels were 19.9, 38.9, and 51.9%, respectively. Ecological dose-response models indicate that catalase and urease were the most Cd-sensitive of the enzymes studied and were suitable indicators of soil quality in high geological background areas. Structural equation modeling (SEM) indicates that soil properties influenced sensitive enzymes through various pathways, indicating that soil properties were factors determining Cd inhibition of enzyme activities. This suggests that Cd concentrations and soil physicochemical properties under a range of environmental conditions should be considered in addressing soil Cd pollution.


Assuntos
Celulases , Oryza , Poluentes do Solo , Cádmio/análise , Solo/química , Catalase , Urease/metabolismo , Poluentes do Solo/análise , China , Oryza/metabolismo
3.
J Hazard Mater ; 465: 133211, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38101008

RESUMO

Water-dispersible colloids (WDCs) are vital for trace element migration, but there is limited information about the abundance, size distribution and elemental composition of WDC-bound thallium (Tl) and arsenic (As) in mining-contaminated soils and sediments solutions. Here, we investigated the potential mobilization of WDC-bound Tl and As in soils and sediments in a typical Tl/As-contaminated area. Ultrafiltration results revealed on average > 60% of Tl and As in soil solution (< 220 nm) coexisted in colloidal form whereas Tl and As in sediment solution primarily existed in the truly dissolved state (< 10 kDa) due to increased acidity. Using AF4-UV-ICP-MS and STEM-EDS, we identified Fe-bearing WDCs in association with aluminosilicate minerals and organic matter were main carriers of Tl and As. SAED further verified jarosite nanoparticles were important components of soil WDC, directly participating in the migration of Tl and As. Notably, high pollution levels and solution pH promoted the release of Tl/As-containing WDCs. This study provides quantitative and visual insights into the distribution of Tl and As in WDC, highlighting the important roles of Fe-bearing WDC, soil solution pH and pollution level in the potential mobilization of Tl and As in contaminated soils and sediments.

5.
Arterioscler Thromb Vasc Biol ; 43(11): e443-e467, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37767706

RESUMO

BACKGROUND: Inflammation contributes to the pathogenesis of atherosclerosis. But little is known about the potential benefits of inflammatory cells to atherosclerosis. The aim of this study was to investigate the function of inflammatory cells/endothelium axis and determine whether and how inflammatory cell-derived MYDGF (myeloid-derived growth factor) inhibited endothelial LDL (low-density lipoprotein) transcytosis. METHODS: In in vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of inflammatory cell-derived MYDGF on LDL transcytosis. We generated monocyte/macrophage-targeted MYDGF-null mice on an Ldlr (LDL receptor)-/- background in the loss-of-function strategy and restored the inflammatory cell-derived MYDGF by bone marrow transplantation and inflammatory cell-specific overexpression of MYDGF mice model in the gain-of-function strategy. In in vitro experiments, coculture experiments between primary mouse aortic endothelial cells and macrophages and mouse aortic endothelial cells supplemented with or without recombinant MYDGF were conducted. RESULTS: Inflammatory cell-derived MYDGF deficiency aggravated endothelial LDL transcytosis, drove LDL uptake by artery wall, and thus exacerbated atherosclerosis in vivo. Inflammatory cell-derived MYDGF restoration by bone marrow transplantation and inflammatory cell MYDGF overexpression alleviated LDL transport across the endothelium, prevented LDL accumulation in the subendothelial space, and subsequently ameliorated atherosclerosis in vivo. Furthermore, in the in vitro study, macrophages isolated from MYDGF+/+ mice and recombinant MYDGF attenuated LDL transcytosis and uptake in mouse aortic endothelial cells. Mechanistically, MYDGF inhibited MAP4K4 (mitogen-activated protein kinase kinase kinase kinase isoform 4) phosphorylation, enhanced activation of Akt (protein kinase B)-1, and diminished the FoxO (forkhead box O) 3a signaling cascade to exert protective effects of MYDGF on LDL transcytosis and atherosclerosis. CONCLUSIONS: The findings support a role for inflammatory cell-derived MYDGF served as a cross talk factor between inflammatory cells and endothelial cells that inhibits LDL transcytosis across endothelium. MYDGF may become a novel therapeutic drug for atherosclerosis, and the beneficial effects of inflammatory cell in atherosclerosis deserve further attention.


Assuntos
Aterosclerose , Células Endoteliais , Camundongos , Animais , Células Endoteliais/metabolismo , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Lipoproteínas LDL/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Camundongos Knockout , Transcitose , Endotélio/metabolismo
6.
Medicine (Baltimore) ; 102(27): e34217, 2023 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-37417620

RESUMO

RATIONALE: Rare tumor-induced osteomalacia (TIO) usually resulted in bone pain, fragility fractures and muscle weakness in clinical, which is caused by the reduced phosphate reabsorption, thus impaired mineralization of the bone matrix and free energy transfer. The specific problems in postsurgical patients are obscure although surgical removal of the tumor is the only definitive treatment. Here, we documented a female TIO patient who suffered more severe bone pain and muscle spasms post-operation. Further, we presented and discussed our explanation for the unexpected symptoms. PATIENT CONCERNS: The main symptoms were whole-body pain and muscle weakness. The patient also presented with osteoporosis and multiple fractures. DIAGNOSIS: Elevated serum fibroblast growth factor 23 (FGF23) level and hypophosphatemia indicated the diagnosis of TIO. Positron emission tomography (PET)/computed tomography (CT) with 68 Ga-DOTATATE located the tumor in the dorsolateral part of the left foot. Histopathological examinations confirmed the diagnosis. INTERVENTIONS: The tumor was surgically removed immediately after the diagnosis of TIO and localization of the tumor. Postoperatively, calcium carbonate supplement treatment was continued. OUTCOMES: Two days after surgery, the serum FGF23 level was decreased to the normal range. Five days after surgery, N-terminal propeptide of type I procollagen and ß-CrossLaps (ß-CTx) had a remarkable increase. A month after surgery, the patient N-terminal propeptide of type I procollagen and ß-CTx levels were decreased obviously, and serum FGF23, phosphate and 24h urinary phosphate were in the normal range. LESSONS: We report a female patient who presented with osteoporosis and fractures. She was found with an elevation of FGF23 and diagnosis with TIO after PET/CT scanning. After surgically removing the tumor, the patient experienced more severe bone pain and muscle spasms. Active bone remodeling might be the reason for the symptoms. Further study will reveal the specific mechanism for this abnormal bone metabolism.


Assuntos
Reabsorção Óssea , Fraturas Ósseas , Hipofosfatemia , Neoplasias de Tecido Conjuntivo , Osteomalacia , Osteoporose , Síndromes Paraneoplásicas , Humanos , Feminino , Neoplasias de Tecido Conjuntivo/complicações , Neoplasias de Tecido Conjuntivo/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Osteomalacia/etiologia , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/diagnóstico , Hipofosfatemia/etiologia , Fosfatos , Fraturas Ósseas/complicações , Dor/etiologia , Osteoporose/complicações , Debilidade Muscular , Espasmo , Fatores de Crescimento de Fibroblastos
7.
J Med Virol ; 95(6): e28872, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37310134

RESUMO

China is an epidemic area of hepatitis E, and the serum prevalence data is very important for formulating prevention and control strategies. However, almost all related research in the past decade are cross-sectional studies. In this study, we analyzed the serological data from 2012 to 2021 in Chongqing for 10 consecutive years. We found that the positive rate of hepatitis E IgG antibody increased gradually, from 1.61% in January 2012 to 50.63% in December 2021. The autoregressive integrated moving average model was used to predict the trend, and it was found that it will continue to show an upward trend in the recent future. In contrast, the positive rate of IgM and clinical incidence of hepatitis E showed a relatively stable trend. Although the positive rate of antibodies gradually increased with age, there was no significant difference in the age distribution of the subjects each year. Therefore, these results suggest that the accumulated infection of hepatitis E in Chongqing may be gradually increasing, but the clinical incidence rate remains unchanged, which provides a new concern for formulating prevention and control strategies.


Assuntos
Vírus da Hepatite E , Hepatite E , Humanos , Hepatite E/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Estudos Soroepidemiológicos , Fatores de Tempo , China/epidemiologia , Anticorpos Anti-Hepatite , Imunoglobulina G , Imunoglobulina M
8.
Virol J ; 20(1): 77, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095526

RESUMO

BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 ± 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 ± 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.


Assuntos
Colecistite Acalculosa , Colecistite , Hepatite E , Peritonite , Masculino , Feminino , Humanos , Colecistite Acalculosa/complicações , Hepatite E/complicações , Doença Aguda , Colecistite/complicações , Colecistite/epidemiologia , Peritonite/etiologia , Ácidos e Sais Biliares
9.
Sensors (Basel) ; 23(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36679646

RESUMO

Some recent studies use a convolutional neural network (CNN) or long short-term memory (LSTM) to extract gait features, but the methods based on the CNN and LSTM have a high loss rate of time-series and spatial information, respectively. Since gait has obvious time-series characteristics, while CNN only collects waveform characteristics, and only uses CNN for gait recognition, this leads to a certain lack of time-series characteristics. LSTM can collect time-series characteristics, but LSTM results in performance degradation when processing long sequences. However, using CNN can compress the length of feature vectors. In this paper, a sequential convolution LSTM network for gait recognition using multimodal wearable inertial sensors is proposed, which is called SConvLSTM. Based on 1D-CNN and a bidirectional LSTM network, the method can automatically extract features from the raw acceleration and gyroscope signals without a manual feature design. 1D-CNN is first used to extract the high-dimensional features of the inertial sensor signals. While retaining the time-series features of the data, the dimension of the features is expanded, and the length of the feature vectors is compressed. Then, the bidirectional LSTM network is used to extract the time-series features of the data. The proposed method uses fixed-length data frames as the input and does not require gait cycle detection, which avoids the impact of cycle detection errors on the recognition accuracy. We performed experiments on three public benchmark datasets: UCI-HAR, HuGaDB, and WISDM. The results show that SConvLSTM performs better than most of those reporting the best performance methods, at present, on the three datasets.


Assuntos
Aprendizado Profundo , Redes Neurais de Computação , Marcha , Aceleração , Memória de Longo Prazo
11.
Nat Metab ; 4(11): 1573-1590, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36400933

RESUMO

Brown adipose tissue (BAT) activity contributes to cardiovascular health by its energy-dissipating capacity but how BAT modulates vascular function and atherosclerosis through endocrine mechanisms remains poorly understood. Here we show that BAT-derived neuregulin-4 (Nrg4) ameliorates atherosclerosis in mice. BAT-specific Nrg4 deficiency accelerates vascular inflammation and adhesion responses, endothelial dysfunction and apoptosis and atherosclerosis in male mice. BAT-specific Nrg4 restoration alleviates vascular inflammation and adhesion responses, attenuates leukocyte homing and reduces endothelial injury and atherosclerosis in male mice. In endothelial cells, Nrg4 decreases apoptosis, inflammation and adhesion responses induced by oxidized low-density lipoprotein. Mechanistically, protein kinase B (Akt)-nuclear factor-κB signaling is involved in the beneficial effects of Nrg4 on the endothelium. Taken together, the results reveal Nrg4 as a potential cross-talk factor between BAT and arteries that may serve as a target for atherosclerosis.


Assuntos
Tecido Adiposo Marrom , Aterosclerose , Neurregulinas , Animais , Masculino , Camundongos , Tecido Adiposo Marrom/metabolismo , Aterosclerose/metabolismo , Células Endoteliais/metabolismo , Endotélio , Inflamação/metabolismo , Neurregulinas/metabolismo
12.
Sensors (Basel) ; 22(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36298236

RESUMO

This paper considers trajectory a modeling problem for a multi-agent system by using the Gaussian processes. The Gaussian process, as the typical data-driven method, is well suited to characterize the model uncertainties and perturbations in a complex environment. To address model uncertainties and noises disturbances, a distributed Gaussian process is proposed to characterize the system model by using local information exchange among neighboring agents, in which a number of agents cooperate without central coordination to estimate a common Gaussian process function based on local measurements and datum received from neighbors. In addition, both the continuous-time system model and the discrete-time system model are considered, in which we design a control Lyapunov function to learn the continuous-time model, and a distributed model predictive control-based approach is used to learn the discrete-time model. Furthermore, we apply a Kullback-Leibler average consensus fusion algorithm to fuse the local prediction results (mean and variance) of the desired Gaussian process. The performance of the proposed distributed Gaussian process is analyzed and is verified by two trajectory tracking examples.

13.
Medicine (Baltimore) ; 101(36): e30522, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36086691

RESUMO

BACKGROUND: Whether the widespread anti-osteoporosis treatments in postmenopausal women also benefit the change of body composition (lean body mass [LBM] and body fat mass [FM]) remains controversial. In order to solve this issue and find out the most effective treatment, we conducted this meta-analysis. METHODS: We searched the literature, via PubMed, Embase, Scopus, Web of Science, and Cochrane to screen citations from inception to March 26, 2022, for inclusion in this study. Only clinical trials that used anti-osteoporosis treatments in postmenopausal women and displayed the alteration of body composition were included. Stata 14.0 was used for the meta-analysis. RESULTS: Our meta-analysis results presented that: compared with placebo, hormone replacement therapy (HRT) was associated with increased LBM (standardized mean differences [SMD] = 0.32, 95% confidence interval [CI] = 0.02-0.61) and reduced FM (SMD = -0.30, 95% CI = -0.51 to -0.09) in postmenopausal women. Compared with placebo, physical exercise training showed an effect of decreasing FM (SMD = -0.66, 95% CI = -0.94 to -0.38) but not significant influence LBM (SMD = 1.31, 95% CI = -0.29 to 2.91). The network meta-analysis of our study showed that oral estrogen and progestogen plus exercise (OEPE) treatment might be the most effective anti-osteoporosis treatment (surface under the cumulative ranking curve 99.9) to reduce FM in postmenopausal women. CONCLUSIONS: anti-osteoporosis treatments, especially HRT, affect body composition. Furthermore, the combination of HRT and exercise training are the most effective treatment to reduce FM while maintaining LBM.


Assuntos
Osteoporose Pós-Menopausa , Composição Corporal , Exercício Físico , Feminino , Humanos , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-Menopausa
14.
EMBO Rep ; 23(3): e53509, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35068044

RESUMO

Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell-specific myeloid-derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell-specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell-derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)-induced bone loss and age-related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCß-NF-κB and MAPK1/3-STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell-derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders.


Assuntos
Reabsorção Óssea , Interleucinas , Osteogênese , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Osso e Ossos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Feminino , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Interleucinas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteogênese/genética
15.
Calcif Tissue Int ; 110(1): 131-142, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34383111

RESUMO

Osteoarthritis (OA) is characterized by chondrocyte apoptosis and increased degradation of type II collagen. Inflammation is one of the major risk factors involved in the pathophysiology of OA. Neuregulin 4 (Nrg4) plays a protective role in a variety of low-level inflammatory diseases, such as non-alcoholic fatty liver disease, inflammatory bowel disease, or type 2 diabetes mellitus. Here we found that (1) Nrg4 deficiency aggravated the destruction and inflammation of articular cartilage and the apoptosis of chondrocytes in vivo. (2) Nrg4 restoration reversed these changes in vivo. (3) Murine recombinant Nrg4 (rNrg4) suppressed inflammation and apoptosis of chondrocytes and decreased the degradation of extracellular matrix in vitro. (4) Mechanistically, the mitogen-activated protein kinase/c-jun N-terminal kinase (MAPK/JNK) signaling pathway may be involved in the regulation of Nrg4 in the pathophysiology of OA. Therefore, we concluded that Nrg4 alleviated the progression of OA by inhibiting the inflammation, protecting against apoptosis of chondrocyte, and decreasing the degradation of extracellular matrix in a manner involving MAPK/JNK signaling.


Assuntos
Apoptose , Cartilagem Articular , Condrócitos , Neurregulinas/genética , Osteoartrite , Animais , Células Cultivadas , Progressão da Doença , Inflamação , Camundongos , Osteoartrite/genética
16.
J Integr Plant Biol ; 62(11): 1653-1658, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32396228

RESUMO

Cas12b/C2c1 is a newly identified class 2 CRISPR endonuclease that was recently engineered for targeted genome editing in mammals and rice. To explore the potential applications of the CRISPR-Cas12b system in the dicot Arabidopsis thaliana, we selected BvCas12b and BhCas12b v4 for analysis. We successfully used both endonucleases to induce mutations, perform multiplex genome editing, and create large deletions at multiple loci. No significant mutations were detected at potential off-target sites. Analysis of the insertion/deletion frequencies and patterns of mutants generated via targeted gene mutagenesis highlighted the potential utility of CRISPR-Cas12b systems for genome editing in Arabidopsis.


Assuntos
Arabidopsis/metabolismo , Genoma de Planta/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sistemas CRISPR-Cas/genética , Edição de Genes , Mutagênese , Mutação/genética
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(7): 1802-5, 2010 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-20827974

RESUMO

3,5-dimethoxybenzyl alcohol (L1 OH) is a kind of important pharmaceutical intermediate and it is also the starting material of a family of dendrimer LnOH (integer n means the layers of "branch"). A number of articles reported the structure and properties of the L1 OH. However, its molecular vibrational spectra have not been reported up to date. Study of vibrational spectra on L1 OH at the molecular level can provide new information, which is significant for the in-depth study of related molecules of drug and the dendrimer. Recent studies indicated a morphology effect on the light-harvesting functions of dendritic macromolecules. In the present report, the Raman and FTIR spectra of 3,5-dimethoxybenzyl alcohol were measured experimentally. And the density functional theory (DFT) method (B3LYP/6-311G(d,p)) were used to calculate the equilibrium geometry and vibration frequencies of L1 OH. The results showed that the calculated frequencies agree well with the experimental ones. Potential energy distribution of each frequency was worked out by normal mode analysis. Thereafter the authors got a detail assignment of the vibrational frequencies for L1 OH for the first time. Also, the results showed that the DFT is really a useful method in the study of molecular vibrational spectra.


Assuntos
Álcoois/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral Raman
18.
DNA Repair (Amst) ; 8(11): 1321-7, 2009 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-19733517

RESUMO

Expansion of GAA x TTC repeats in FXN gene is associated with decreased frataxin production in Frederich's ataxia patients. To study this effect, we have engineered a set of GAA x TTC repeats in the EcoRI site of lacZ gene of plasmid pUC18 as part of the transcription template of the lacZ gene, while keeping its ORF unchanged. The effects of the GAA x TTC repeats on the lacZ expression were investigated in Escherichia coli JM83 and its mutants deficiency in RNA processing, homologous recombination and DNA repair. We found that transcriptions of the GAA strand with different sizes and organizations displayed normal alpha-complementation when RNase E was functional. By contrast, transcriptions of TTC repeats containing more than 13 triplets failed to support alpha-complementation, showing RNase-independent but length-dependent effects of TTC repeats on lacZ expression. In addition, we also found that functions of SbcCD, a DNA structure specific nuclease, were needed in the RNase E-dependent lacZ expression of the GAA repeats. These suggested that processing of DNA and RNA is essential to the transcription of the repeats-carrying gene in vivo.


Assuntos
DNA Bacteriano/genética , Endorribonucleases/metabolismo , Proteínas de Escherichia coli/metabolismo , Escherichia coli/enzimologia , Exonucleases/metabolismo , Transcrição Gênica , Repetições de Trinucleotídeos , DNA Bacteriano/química , Escherichia coli/química , Óperon Lac , Modelos Moleculares , Conformação de Ácido Nucleico , RNA Mensageiro/química , RNA Mensageiro/genética
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