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1.
Front Neurosci ; 16: 844821, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495045

RESUMO

Background: Single-sex children have been regarded as one of the best subjects to understand the abnormal development patterns of autism spectrum disorders (ASDs). However, the functional connectivity (FC) behind their symptoms is still unknown. Methods: Based on FC analysis, the acquired resting-state functional magnetic resonance imaging (rs-fMRI) data sets, including 86 boys with ASD and 54 normal controls (NC), were used to detect the neural synchronous activity between brain regions. Pearson correlation analysis was used to evaluate the relationship between the abnormal FC value and clinical features. Results: Individuals with ASD showed enhanced FC between the right calcarine and the right lingual gyrus (LG). The right medial orbital frontal cortex also showed increased FC with bilateral inferior temporal gyrus (ITG) [two-tailed, voxel-level p < 0.001, gaussian random field (GRF) correction, cluster-level p < 0.05]. We did not find a correlation between the abnormal FC value and clinical scales. Conclusion: Our study reveals a possible relationship between atypical visual attention and poor learning ability in subjects with ASD, and delayed social language development may be a secondary symptom to ASD.

2.
J Hazard Mater ; 423(Pt B): 127115, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34537635

RESUMO

Lipids are the structural constituents of cell membranes and play crucial roles in plant adaptation to abiotic stresses. The aim of this study was to use glycerolipidomic and transcriptomic to analyze the changes in lipids metabolism induced by cadmium (Cd) exposure in wheat. The results indicated that Cd stress did not decrease the concentrations of monogalactosyldiacyglycerol (MGDG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and phosphatidic acid at 6 h, but decreased digalactosyldoacylglycerol (DGDG), MGDG, PC, phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylserine (PS) and LPC concentrations in wheat root at 24 h. Although the concentrations of highly abundant glycerolipids PC and PE were decreased, the ratios of PC/PE increased thus contributing to wheat adaptation to Cd stress. Cd did not reduce the extent of total lipid unsaturation due to the unchanged concentrations of high abundance species of C36:4, C34:2, C34:3 and C36:6 at 6 h, indicative of their roles in resisting Cd stress. The correlation analysis revealed the glycerolipids species experiencing co-metabolism under Cd stress, which is driven by the activated expression of genes related to glycerolipid metabolism, desaturation and oxylipin synthesis. This study gives insights into the changes of glycerolipids induced by Cd and the roles in wheat adaptation to Cd stress.


Assuntos
Cádmio , Triticum , Cádmio/toxicidade , Fosfatidilcolinas , Estresse Fisiológico , Transcriptoma , Triticum/genética
3.
J Atten Disord ; 26(1): 88-100, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33084494

RESUMO

OBJECTIVE: The present study aimed to examine the effects of SNAP25 on the integration ability of intrinsic brain functions in children with ADHD, and whether the integration ability was associated with working memory (WM). METHODS: A sliding time window method was used to calculate the spatial and temporal concordance among five rs-fMRI regional indices in 55 children with ADHD and 20 healthy controls. RESULTS: The SNAP25 exhibited significant interaction effects with ADHD diagnosis on the voxel-wise concordance in the right posterior central gyrus, fusiform gyrus and lingual gyrus. Specifically, for children with ADHD, G-carriers showed increased voxel-wise concordance in comparison to TT homozygotes in the right precentral gyrus, superior frontal gyrus, postcentral gyrus, and middle frontal gyrus. The voxel-wise concordance was also found to be related to WM. CONCLUSION: Our findings provided a new insight into the neural mechanisms of the brain function of ADHD children.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criança , Lobo Frontal , Humanos , Imageamento por Ressonância Magnética/métodos , Memória de Curto Prazo , Proteína 25 Associada a Sinaptossoma
4.
Pediatr Pulmonol ; 56(12): 3592-3594, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34637610

RESUMO

An isolated sternal cleft is an orphan congenital defect of the sternum that presents from birth to adulthood. We report the case of a 4-day-old newborn with an isolated congenital cleft sternum. We also reviewed the related literature and operative options.


Assuntos
Cardiopatias Congênitas , Anormalidades Musculoesqueléticas , Adulto , Humanos , Recém-Nascido , Anormalidades Musculoesqueléticas/diagnóstico por imagem , Esterno/anormalidades , Esterno/diagnóstico por imagem
5.
Ecotoxicol Environ Saf ; 223: 112623, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34388658

RESUMO

Cadmium (Cd) is present in many soils and, when enter a food chain, represents a major health threat to humans. The existent large variation in grain Cd content amongst wheat genotypes opens prospects for genetic improvement for reduced Cd uptake in this species. However, selecting low-Cd-accumulating varieties comes with a possible caveat of affecting uptake other essential nutrients. In this work, we screened 134 wheat varieties in 3 various field studies and selected 15 high- and 15 low-Cd accumulating varieties in grains for ionomics analysis. Our results showed that high-Cd accumulating varieties also possessed an ability to accumulate mineral elements of calcium, magnesium, manganese, iron and zinc, while varieties with low Cd content were deficient in many essential nutrients and, especially, zinc (Zn). The above data was confirmed in an independent trail involving another 97 wheat varieties. Thus, selecting plants for high Zn accumulation (as a part of biofortification programs) resulted in an inadvertent increase in accumulation of the toxic Cd in wheat. Vice versa, selecting low Cd-accumulating varieties comes with a danger of reducing their Zn content, with major consequences to food quality and human health. We suggest that the above conundrum can be resolved by understanding the structure-function relations of various transporters isoforms involved in Zn and Cd transport and issue-specific mode of their operation, via cell-based phenotyping followed by molecular breeding.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Grão Comestível/química , Humanos , Solo , Poluentes do Solo/análise , Triticum/genética , Zinco/análise
6.
Nucleic Acids Res ; 49(17): 10046-10060, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34417618

RESUMO

Inducing tRNA +1 frameshifting to read a quadruplet codon has the potential to incorporate a non-natural amino acid into the polypeptide chain. While this strategy is being considered for genome expansion in biotechnology and bioengineering endeavors, a major limitation is a lack of understanding of where the shift occurs in an elongation cycle of protein synthesis. Here, we use the high-efficiency +1-frameshifting SufB2 tRNA, containing an extra nucleotide in the anticodon loop, to address this question. Physical and kinetic measurements of the ribosome reading frame of SufB2 identify twice exploration of +1 frameshifting in one elongation cycle, with the major fraction making the shift during translocation from the aminoacyl-tRNA binding (A) site to the peptidyl-tRNA binding (P) site and the remaining fraction making the shift within the P site upon occupancy of the A site in the +1-frame. We demonstrate that the twice exploration of +1 frameshifting occurs during active protein synthesis and that each exploration is consistent with ribosomal conformational dynamics that permits changes of the reading frame. This work indicates that the ribosome itself is a determinant of changes of the reading frame and reveals a mechanistic parallel of +1 frameshifting with -1 frameshifting.


Assuntos
Mudança da Fase de Leitura do Gene Ribossômico/genética , Elongação Traducional da Cadeia Peptídica/genética , Aminoacil-RNA de Transferência/metabolismo , RNA de Transferência/genética , Ribossomos/metabolismo , Anticódon/genética , Sítios de Ligação/genética , Proteínas de Transporte/genética , Códon/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , RNA Mensageiro/genética , Fases de Leitura/genética
7.
Neuropsychiatr Dis Treat ; 17: 2003-2010, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168457

RESUMO

PURPOSE: To analyze the changes in white matter tracts in preschool children with autism spectrum disorder (ASD), and the correlation between these changes and social communication deficits. METHODS: Diffuse tensor imaging was used to assess white matter integrity using tract-based spatial statistics in a sample of 50 right-handed children with ASD aged 2-6 years vis a reference sample of 46 typically developing children aged 2-6 years. We then correlated these significant different fiber tracts between groups with communication and social interaction scores using the Autism Diagnostic Interview-Revised Assessment (ADI-R) Scale. RESULTS: We observed decreased fractional anisotropy (FA) in tracts including the left superior longitudinal fasciculus (SLF), the splenium of the corpus callosum (splCC), the left corticospinal tracts, and the left inferior longitudinal fasciculus (ILF) in children with ASD. Specifically, there was reduced white matter integrity of these tracts in the left cerebral hemisphere. In addition, we found that the decreased FA of left SLF and ILF was negatively associated with the ADI-R scores in children with ASD. CONCLUSION: The structural integrity of some white matter tracts in the five-level anatomical model for the social communication was reduced. The reduced integrity white matter that we observed primarily in the left cerebral hemisphere may be a neural substrate of social communication deficits in preschool children with ASD, and we speculate that the reduction is associated with the severity of social interaction. The reduced FA of the splCC might be a substantial biomarker for children with ASD.

8.
Front Neurosci ; 15: 644543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828452

RESUMO

OBJECTIVES: The study was aimed at investigating the alterations of local spontaneous brain activity in preschool boys with autism spectrum disorders (ASD). METHODS: Based on regional homogeneity (ReHo), the acquired resting state functional magnetic resonance imaging (fMRI) data sets, which included 86 boys with ASD and 54 typically developing (TD) boys, were used to detect regional brain activity. Pearson correlation analysis was used to study the relationship between abnormal ReHo value and the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), developmental quotient, and age. RESULTS: In the ASD group, we found increased ReHo in the right calcarine as well as decreased ReHo in the opercular part of the left inferior frontal gyrus, the left middle temporal gyrus, the left angular gyrus, and the right medial orbital frontal cortex (p < 0.05, false discovery rate correction). We did not find a correlation between the results of brain regions and the CARS, ABC, and age. CONCLUSIONS: Our study found spontaneous activity changes in multiple brain regions, especially the visual and language-related areas of ASD, that may help to further understand the clinical characteristics of boys with ASD.

9.
Chembiochem ; 22(10): 1775-1778, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33458897

RESUMO

Ribosomal frameshifting is an important pathway used by many viruses for protein synthesis that involves mRNA translocation of various numbers of nucleotides. Resolving the mRNA positions with subnucleotide precision will provide critical mechanistic information that is difficult to obtain with current techniques. We report a method of high-resolution DNA rulers with subnucleotide precision and the discovery of new frameshifting intermediate states on mRNA containing a GA7 G motif. Two intermediate states were observed with the aid of fusidic acid, one at the "0" reading frame and the other near the "-1" reading frame, in contrast to the "-2" and "-1" frameshifting products found in the absence of the antibiotic. We termed the new near-"-1" intermediate the Post(-1*) state because it was shifted by approximately half a nucleotide compared to the normal "-1" reading frame at the 5'-end. This indicates a ribosome conformation that is different from the conventional model of three reading frames. Our work reveals uniquely precise mRNA motions and subtle conformational changes that will complement structural and fluorescence studies.


Assuntos
RNA Mensageiro/metabolismo , Ribossomos/metabolismo , Sequência de Bases , Mudança da Fase de Leitura do Gene Ribossômico , Ácido Fusídico/química , Biossíntese de Proteínas , RNA Mensageiro/química , Fases de Leitura/genética
10.
Eur Arch Psychiatry Clin Neurosci ; 271(5): 823-833, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32124022

RESUMO

Codeine-containing cough syrup (CCS) is considered as one of the most popular drug of dependence among adolescents because of its inexpensiveness and easy availability. However, its relationship with neurobiological effects remains sparsely explored. Herein, we examined how high-impulse behaviours relate to changes in the brain structural networks. Forty codeine-containing cough syrup dependent (CCSD) users and age-, gender-, and number of cigarettes smoked per day -matched forty healthy control (HC) subjects underwent structural brain imaging via MRI. High-impulse behaviour was assessed using the 30-item self-rated Barratt Impulsiveness Scale (BIS-11), and structural networks were constructed using diffusion tensor imaging and AAL-90 template. Between-group topological metrics were compared using nonparametric permutations. Benjamin-Hochberg false discovery rate correction was used to correct for multiple comparisons (P < 0.05). The relationships between abnormal network metrics and clinical characteristics of CCS dependent (BIS-11 total score, CCS- dependent duration and mean dose) were examined by Spearman's correlation. Structural networks of the CCSD group demonstrated lower small-world properties than those of the HC group. Abnormal changes in nodal properties among CCSD users were located mainly in the frontal gyrus, inferior parietal lobe and olfactory cortex. NBS analysis further indicated disrupted structural connections between the frontal gyrus and multiple brain regions. There were significant correlations between abnormal nodal properties of the frontal gyrus and clinical characteristics (BIS-11 total score, CCS dependent duration and mean dose) in the CCSD group. These findings suggest that the high-impulse behavioural expression in CCS addiction is associated with widespread brain regions, particularly within those in the frontal cortex. Aberrant brain regions and disrupted connectivity of structural network may be the bases of neuropathology for underlying symptoms of high-impulse behaviours in CCSD users, which may provide a novel sight to better treat and prevent codeine dependency in adolescents.


Assuntos
Comportamento Impulsivo , Rede Nervosa , Substância Branca , Adolescente , Antitussígenos/efeitos adversos , Codeína/efeitos adversos , Tosse/tratamento farmacológico , Imagem de Tensor de Difusão , Humanos , Comportamento Impulsivo/fisiologia , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/psicologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
11.
J Psychiatr Res ; 130: 333-341, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32889355

RESUMO

PURPOSE: Codeine-containing cough syrup (CCS) is considered among the most popular drugs of abuse in adolescents worldwide. Accurate prediction and identification of CCS dependent (CCSD) users are crucial. This study aimed to identify a brain-connectome-based predictor of CCSD using a machine learning model based on a ten-fold cross-validation logistic regression (LR) classifier. METHODS: 40 CCSD users and 40 healthy control (HC) subjects underwent functional magnetic resonance imaging to construct weight functional networks. Partial correlation analysis was used to analyze relations between abnormal network metrics and clinical characteristics (BIS total scores, CCS abuse duration, and mean CCS dose) in CCSD. A ten-fold cross-validation LR classifier was used to classify CCSD users and HC subjects. RESULTS: The CCSD group showed significantly abnormal nodes and connections in the right posterior cingulate, right middle insula, bilateral prefrontal cortex, parietal lobe, temporal lobe, occipital lobe, and cerebellum. Furthermore, higher characteristic path length and lower clustering coefficient (Cp), global efficiency, and local efficiency (Eloc) were observed in the global topologies in CCSD. The abnormal global properties (Cp and Eloc) and node properties of the prefrontal cortex were significantly correlated with clinical characteristics (BIS-11 scores, CCS abuse duration) in CCSD. The LR classifier models demonstrated accuracy, sensitivity, specificity, precision, and AUC of 82.5%, 82.5%, 82.5%, 76.8%, and 82.5%. CONCLUSIONS: These data demonstrate that abnormal functional connectome may be closely linked to clinical characteristics in CCSD. Functional connectome-based biomarkers can be a powerful tool for personalized diagnosis of CCSD in the future.


Assuntos
Conectoma , Adolescente , Biomarcadores , Encéfalo/diagnóstico por imagem , Codeína , Tosse/induzido quimicamente , Tosse/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
12.
Ecotoxicol Environ Saf ; 197: 110621, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32304924

RESUMO

Antimony (Sb) excess accumulation in edible parts of crops causes potential risks to human health. However, knowledge about the mechanisms of its accumulation within vegetable plants is still not well known. Here, we investigated the physiological processes of Sb involved in symplastic and apoplastic absorption, compartmentation by roots, and translocation in xylem in Brassica parachinensis L. exposed to antimonate (SbV) and antimonite (SbIII) forms. The results showed that plants treated with SbIII emerged to be more toxic than SbV as proved by the lower biomass and the higher concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in plant tissues, especially at high dosages. The Sb concentration showed more in shoots but less in roots treated with SbV than with SbIII. The total Sb accumulation was higher under the SbV treatment than the SbIII treatment, mainly due to the higher accumulation in shoots. Additionally, the Sb concentration in symplastic flow of roots was higher exposed to SbV than SbIII, while no differences were found for the Sb concentration in apoplastic flow between them. Moreover, the Sb concentration in cell walls of roots was higher exposed to SbIII than SbV, especially at high levels. Furthermore, the Sb concentration in xylem was higher exposed to SbV than SbIII, and a greatly positive correlation was observed between the Sb concentrations in xylem and shoots. Overall, these findings revealed that vegetable plants accumulated more SbV than SbIII in edible parts mainly due to xylem translocation rather than root absorption.


Assuntos
Antimônio/farmacocinética , Brassica/metabolismo , Absorção Fisiológica , Antimônio/toxicidade , Transporte Biológico , Brassica/efeitos dos fármacos , Parede Celular/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Raízes de Plantas/metabolismo , Xilema/metabolismo
13.
Ecotoxicol Environ Saf ; 189: 110010, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31787381

RESUMO

Nitrogen (N) forms not only affect cadmium (Cd) accumulation in plants, but also affect plant resistance to Cd toxicity. However, few researches have been reported underlying the mechanism of the relationship between nitrogen forms and plant resistance under Cd exposure. Here, we explored the mechanism on how different NO3-/NH4+ ratios affect antioxidase system and the glutathione-ascorbate cycle under five different ratios of NO3-/NH4+ (1:0, 2:1, 1:1, 1:2, 0:1) and three dosages of Cd exposure (0, 1, 5 µmol L-1 Cd) in rice (Oryza sativa L.). The results showed that high NO3- and high Cd exposure both significantly inhibited tissue growth of rice plants, and this inhibiting trend was mitigated with increasing NH4+ ratios as proved by the increased biomass and the decreased concentrations of malonaldehyde (MDA) and hydrogen peroxide (H2O2), as well as the levels of Cd contents in rice tissues. Additionally, high NH4+ ratios elevated the SOD activities in rice tissues, especially at high Cd treatment. However, other two antioxidases (CAT and APX) were insensitive to changes of NO3-/NH4+ ratios (except the full NO3-). Furthermore, high NH4+ ratios induced increasing of the efficiency of glutathione-ascorbate cycle (GSH-AsA) under two levels of Cd exposure, as evidenced by increasing concentrations of GSH and AsA and the activities of GR and DHAR in rice tissues. Overall, these results revealed that ammonium nutrition caused an enhancement resistance to Cd stress in rice plants was responsible for increasing of partial antioxidase system and the efficiencies of GSH-AsA cycle.


Assuntos
Compostos de Amônio/farmacologia , Ácido Ascórbico/metabolismo , Cádmio/toxicidade , Glutationa/metabolismo , Oryza/metabolismo , Compostos de Amônio/análise , Cádmio/metabolismo , Peróxido de Hidrogênio/metabolismo , Malondialdeído/metabolismo , Nitratos/análise , Nitratos/farmacologia , Oryza/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo
14.
Front Neurosci ; 13: 806, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31427923

RESUMO

Neuroimaging studies have shown that autism spectrum disorders (ASDs) may be associated with abnormalities in brain structures and functions at rest as well as during cognitive tasks. However, it remains unclear if functional connectivity (FC) of all brain neural networks is also changed in these subjects. In this study, we acquired functional magnetic resonance imaging scans from 93 children with ASD and 79 matched healthy subjects. Group independent component analysis was executed for all of the participants to estimate FC. One-sample t-tests were then performed to obtain the networks for each group. Group differences in the different brain networks were tested using two-sample t-tests. Finally, relationships between abnormal FC and clinical variables were investigated with Pearson's correlation analysis. The results from one-sample t-tests revealed nine networks with similar spatial patterns in these two groups. When compared with the controls, children with ASD showed increased connectivity in the right dorsolateral superior frontal gyrus and left middle frontal gyrus (MFG) within the occipital pole network. Children with ASD also showed decreased connectivity in the left gyrus rectus, left middle occipital gyrus, right angular gyrus, right MFG and right inferior frontal gyrus (IFG), orbital part within the lateral visual network (LVN), the left IFG, right precuneus, and right angular gyrus within the left frontoparietal (cognition) network. Furthermore, the mean FC values within the LVN showed significant positive correlations with total score of the Childhood Autism Rating Scale. Our findings indicate that abnormal FC extensively exists within some networks in children with ASD. This abnormal FC may constitute a biomarker of ASD. Our results are an important contribution to the study of neuropathophysiological mechanisms in children with ASD.

15.
J Vis Exp ; (149)2019 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-31329177

RESUMO

The ribosome translocation refers to the ribosomal movement on the mRNA by exactly three nucleotides (nt), which is the central step in protein synthesis. To investigate its mechanism, there are two essential technical requirements. First is single-nt resolution that can resolve normal translocation from frameshifting, during which the ribosome moves by other than 3 nt. The second is the capability to probe both the entrance and exit sides of mRNA in order to elucidate the whole picture of translocation. We report the dual DNA ruler assay that is based on the critical dissociation forces of DNA-mRNA duplexes, obtained by force-induced remnant magnetization spectroscopy (FIRMS).  With 2-4 pN force resolution, the dual ruler assay is sufficient to distinguish different translocation steps. By implementing a long linker on the probing DNAs, they can reach the mRNA on the opposite side of the ribosome, so that the mRNA position can be determined for both sides. Therefore, the dual ruler assay is uniquely suited to investigate the ribosome translocation, and nucleic acid motion in general. We show representative results which indicated a looped mRNA conformation and resolved normal translocation from frameshifting.


Assuntos
DNA/genética , RNA Mensageiro/genética , Ribossomos/genética , Mudança da Fase de Leitura do Gene Ribossômico , Conformação Molecular , Conformação de Ácido Nucleico , Nucleotídeos/metabolismo , Biossíntese de Proteínas , RNA de Transferência/metabolismo
16.
Chembiochem ; 20(23): 2927-2935, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31194278

RESUMO

During ribosome translocation, the elongation factor EF-G undergoes large conformational change while maintaining its contact with the moving tRNA. We previously measured a power stroke accompanying EF-G catalysis, which was consistent with structural studies. However, the role of power stroke in translocation fidelity remains unclear. Here, we report quantitative measurements of the power strokes of structurally modified EF-Gs by using two different techniques and reveal the correlation between power stroke and translocation efficiency and fidelity. We discovered that the reduced power stroke only lowered the percentage of translocation but did not introduce translocation error. The established force -structure-function correlation for EF-G indicates that power stroke drives ribosomal translocation, but the mRNA reading frame is probably maintained by ribosome itself. Furthermore, the microscope detection method reported here can be simply implemented for other biochemical applications.


Assuntos
Fator G para Elongação de Peptídeos/química , RNA Mensageiro/química , Ribossomos/química , Sequência de Bases , DNA/química , Escherichia coli/química , Ácido Fusídico/química , Microscopia , Biossíntese de Proteínas , RNA de Transferência/química
17.
Appl Phys Lett ; 113(19): 193702, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-30473584

RESUMO

Atomic magnetometry and ultrasound, as individual techniques, have been used extensively in various physical, chemical, and biomedical fields. Their combined application, however, has been rare. We report that super-resolution force spectroscopy, which is based on the integration of the two techniques, can find unique biophysical applications in studying drug-DNA interactions. The precisely controlled ultrasound generates acoustic radiation force on the biological systems labeled with magnetic microparticles. A decrease in the magnetic signal, measured by an automated atomic magnetometer, indicates that the acoustic radiation force equals the binding force of the biological system. With 0.5 pN force resolution, we were able to precisely resolve three small molecules binding with two DNA sequences and quantitatively reveal the effect of a single hydrogen bond. Our results indicate that the increases in DNA binding force caused by drug binding correlate with the enthalpy instead of free energy, thus providing an alternative physical parameter for optimizing chemotherapeutic drugs.

18.
RNA Biol ; 15(11): 1392-1398, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30345881

RESUMO

The precise 3-nucleotide movement of mRNA is critical for translation fidelity. One mRNA translocation error propagates to all of the following codons, which is detrimental to the cell. However, none of the current methods can reveal the mRNA dynamics near the ribosome entry site, which limits the understanding of this important issue. We have developed an assay of dual DNA rulers that provides such capability. By uniquely probing both the 3'- and 5'-ends of mRNA, we observed an antibiotic-trapped intermediate state that is consistent with a ribosomal conformation containing mRNA asymmetric partial displacements at its entry and exit sites. Based on the available ribosome structures and computational simulations, we proposed a 'looped' mRNA conformation, which suggested a stepwise 'inchworm' mechanism for ribosomal translocation. The same 'looped' intermediate state identified with the dual rulers persists with a '-1' frameshifting motif, indicating that the branching point of normal and frameshifting translocations occurs at a later stage of translocation.


Assuntos
Conformação de Ácido Nucleico , Biossíntese de Proteínas/genética , RNA Mensageiro/química , Ribossomos/química , Códon/química , Códon/genética , Escherichia coli/genética , Sítios Internos de Entrada Ribossomal , Conformação Molecular , RNA Mensageiro/genética , Ribossomos/genética
19.
Ecotoxicol Environ Saf ; 166: 157-164, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30267988

RESUMO

Silicon (Si) and selenium (Se) are beneficial for many higher plants when grown on stress conditions. However, the mechanisms underlying the differential effects between foliar Si and Se in alleviation of plant toxicity exposed to cadmium (Cd) stress are remained unclear. In this study, we investigated the discrepant mechanisms of foliar Si and Se on Cd absorption and compartmentation by roots, its translocation in xylem, and the antioxidant system within Chinese flowering cabbage (Brassica campestris L. ssp. chinensis var. utilis) under low and high Cd stress. Results showed that plant growth was significantly enhanced by foliar additions of Si or/and Se according to an increased plant tissue biomass at high Cd exposure. In addition, the foliar coupled addition of Si and Se showed little effects on the concentrations of Si or Se in plant tissues in comparison with the single addition of foliar Si or Se respectively. The foliar Si alone or combined with Se markedly reduced the Cd concentrations in plant shoots under two Cd treatments. This might be explained by the lower Cd concentrations in symplast and apoplast and the higher Cd concentrations in cell walls of plant roots, and the lower Cd concentrations in xylem sap. However, no great changes in these values were observed under the treatments of foliar Se alone. Moreover, the foliar additions of Si or/and Se all increased the antioxidant enzyme activities of SOD, CAT and APX in plant tissues, especially at high Cd dosage. No significant differences in the increasing degrees of these three antioxidant enzymes were found between the foliar Si and Se treatments. However, only the foliar Se alone or combined with Si markedly promoted the antioxidant enzyme activities of GR and DHAR in plant tissues. Our findings demonstrate that the alleviation of Cd toxicity by foliar Si maybe mainly responsible for inhibition of Cd absorption and its translocation to plant shoots, reinforcing its compartmentation into root cell walls, whilst enhancing the antioxidant enzyme system may be employed by foliar Se.


Assuntos
Brassica/metabolismo , Cádmio/farmacocinética , Selênio/farmacologia , Silício/farmacologia , Absorção Fisiológica , Antioxidantes/metabolismo , Transporte Biológico , Biomassa , Brassica/enzimologia , Brassica/crescimento & desenvolvimento , Parede Celular/metabolismo , Brotos de Planta/metabolismo , Xilema/metabolismo
20.
Ecotoxicol Environ Saf ; 164: 589-596, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30149358

RESUMO

Most plants exhibit strong tolerance to excess molybdenum (Mo). However, the metabolic profile and tolerance mechanisms of plants in response to excess Mo remain unknown. We comprehensively analyzed changes in the metabolic profiles of leaves and roots in soybean (Glycine max L.) seedlings cultured under normal-Mo and excess-Mo conditions by using ultra performance liquid chromatography (UPLC) combined with MS/MS (mass spectrometry). There were 42 differential metabolites in the roots and 19 differential metabolites in the leaves in response to excess Mo stress. In roots, the organic acids, levels of gluconic acid, D-glucarate and citric acid increased by 107.63-, 4.42- and 2.87-folds after excess Mo exposure. Several hormones (salicylic acid, jasmonic acid) and lipids (PG, MG, DG etc) also increased significantly under excess Mo condition. Metabolites related to ascorbate-glutathione metabolism and flavonoid and isoflavone biosynthesis notably accumulated in roots. Only lipid metabolism and salicylic acid accumulation were induced in leaves under excess Mo stress. It is speculated that organic compounds such as 2-oxoarginine, L-nicotine, gluconic acid, D-glucurate, and citric acid played important roles to chelate Mo and reduce its toxicity. Signaling molecules (JA, SA, and some lipids) and non-enzyme antioxidants such as flavonoids/isoflavones act synergistically to detoxify ROS and contribute to Mo tolerance in soybean seedlings. More metabolic pathways were induced by Mo excess in roots than in leaves, suggesting that roots play more implant role in Mo tolerance.


Assuntos
Metabolômica , Molibdênio/metabolismo , Soja/metabolismo , Ciclopentanos/metabolismo , Exposição Ambiental , Metaboloma , Oxilipinas/metabolismo , Folhas de Planta/metabolismo , Raízes de Plantas/metabolismo , Ácido Salicílico/metabolismo , Plântula/metabolismo
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