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1.
Protein Expr Purif ; 166: 105521, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31654735

RESUMO

Nuclear magnetic resonance (NMR) spectroscopy is a primary structural biology method to characterize protein dynamics in solution. For large macromolecular systems, methyl-labeling in a perdeuterated background significantly improves the relaxation properties, while providing sensitive probes for structure and dynamics analysis. However, how to prepare methyl-labeled proteins, especially for functional eukaryotic proteins, remains to be a major bottleneck in this field. Due to its advantages in eukaryotic co-translational and post-translational modification, as well as high-density fermentation, Pichia pastoris has been a cost-effective platform strain for 13C, 15N-labeling and deuterium labeling since the early 2000's. Recently, some substantial progress has been made in methyl-labeling, such as the feasibility of 13C isoleucine δ1 methyl-labeling in perdeuterated background and the increased uptake of the Val/Leu precursor. Here, we systematically introduce the isotope-labeling strategies in P. pastoris, including strain engineering and detailed fermentation protocols in 13C, 15N-labeling and methyl-labeling, providing instructions and guidance for the future improvement of sample preparation for NMR spectroscopy.

2.
J Exp Child Psychol ; 189: 104703, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31655228

RESUMO

From an early age, children are able to use surface layout geometry and landmarks to search for a hidden toy when disoriented. Theoretical debate remains regarding whether children represent locations based on the global environment or on local cues. Exploring whether children construct and use the relationships between discrete locations of the global environment can provide direct evidence regarding this issue. We investigated young children's representation of two geometric relationships: diagonal relationships (Experiment 1) and same-side relationships (Experiment 2). Children (4- and 5-year-olds) were tested in a square room with a distinctively colored wall. Children completed two tasks. In a two-location task, children watched two toys hidden in two corners that formed one of the two relationships. After disorientating children, the experimenter uncovered one toy and children searched for the other one (target). In a one-location task, only one toy was hidden. In both experiments, children's performance was better in the two-location task than in the one-location task. Furthermore, accuracy in the two-location task of Experiment 1, in which the two corners formed a diagonal relationship, was higher than that of Experiment 2, in which the two corners formed a same-side relationship and a correct location required the combination of this relationship and landmark. These findings suggest that at least by 4 years of age, children can construct geometric relationships between individual corners in their spatial representation and support the global accounts of young children's location coding.

3.
J Nanosci Nanotechnol ; 20(4): 2442-2451, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31492260

RESUMO

Two methods of TiO2 addition were applied to prepare hydroxyapatite/TiO2 (HA/TiO2) composite, i.e., in-situ hydrolysis TiO2 in HA powders (N-HA/TiO2) and mixing commercial nano-sized HA and TiO2 powder (C-HA/TiO2). Effects of TiO2 addition methods and sintering temperatures on phase, microstructure and microhardness were investigated for pressureless sintered HA/TiO2 composites, and pure HA was investigated for comparison. Results show that TiO2 from both in-situ hydrolysis and mixing commercial powder presented similar effects on phase structures and composition, and trended to chemically react with HA in the HA/TiO2 composites at high sintering temperature. Weight loss for different composites was investigated by thermal analysis. Sintering behavior for two different composite was also discussed. The TiO2 from in-situ hydrolysis can effectively enhance the TiO2 distribution and densification for the N-HA/TiO2 composites. Both two different composites showed typical grain growth and pore formation with the increase of sintering temperature. The N-HA/TiO2 composite had a lower porosity, higher shrinkage and microhardness than that of C-HA/TiO2 composite at sintering temperature from 700 °C to 1100 °C.

4.
J Hazard Mater ; 383: 121169, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31520931

RESUMO

Nickel (Ni) contamination in soils, at high concentrations, is considered to be very common. Knowledge of the total content of Ni is frequently insufficient to estimate environmental risk. Our explored findings showed that the earthworms adding reduced the available Ni, along with the superior performance of HCl than CaCl2. The bioaccumulation of Ni in earthworms was aggravated with increasing Ni dosage and exposure time. Bioaccumulation factor was significantly correlated with the extractable Ni, which was the most suitable predicting the variations of Ni bioavailability. LC50 of earthworms on 7 and 14 days were 1202.444 mg kg-1 and 1069.324 mg kg-1, respectively along with the recovery rate in 500 mg kg-1 Ni polluted soil reached up to 92.5%. Earthworms' respiration was sensitive presenting a significant dose-effect relationship with the Ni concentration. Five biochemical indices in earthworms were induced along with the relevance of a dose- and time-response pattern. Additionally, histological damage in earthworm's body wall, intestine and seminal vesicles were observed under high level of Ni exposure. Overall, we believe that our current study will open a new window for deeper insights into the potential availability of Ni along with other associated metals on the function of soil ecosystem.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31525458

RESUMO

Cladocera are small freshwater crustaceans that have attracted considerable attention in recent years. They are commonly used for studying senescence. In this study, we used LC-MS/MS with eight-plex iTRAQ to perform a comparative proteomic analysis of senescence in Daphnia pulex. Of 3076 primordial proteins, 2325 were credible (the remaining were low-confidence proteins) and 247 significantly differentially expressed proteins (DEPs). Of the latter, 87, 91, and 69 DEPs were identified in the Day 15 vs. Day 5, Day 20 vs. Day 5, and Day 25 vs. Day 5 groups, respectively. Gene ontology enrichment analysis showed that oxidative damage may be the main cause of senescence in D. pulex. Using Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that the peroxisome pathway played an important role in aging. Our results suggest that D. pulex alleviates excessive oxidative damage by altering key enzymes involved in carbohydrate and protein metabolism.

6.
Waste Manag ; 101: 180-187, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622863

RESUMO

With the rapid development of photovoltaic industry, the recycling of waste solar photovoltaic (PV) panels is becoming a critical and global challenge. Considering PV panels recycling is significantly effective and worthwhile to save natural resources and reduce the cost of production, how to selectively recycle valuable components of PV panels is the hot and dominant topic. Different from current mechanical crushing, heat treatment and chemical operation processes, novel and environment-friendly recycling approaches by using high voltage pulse discharge in water, called high voltage fragmentation (HVF), was discussed under different discharge conditions. The results showed that discharging across surface and interior of PV panels produced ablation round holes, sputter metal particles and dendritic channels. The average particle size decreased with the ascent of pulse number and voltage amplitude. Considering the energy consumption, the optimal condition of HVF in this paper was 160 kV for 300 pulses with the energy consumption of 192.99 J/g, crushing the PV panels into particles of 4.1 mm in average (13.7% of the initial size). More particle was distributed among the 0.1-2 mm size fractions as the energy increased. Selective fragmented products, such as Cu, Al, Pb, Ag and Sn, are concentrated on the fractions under 1 mm. Finally, hybrid crushing energy consumption model combined with fractal theory was discussed, which presented close relationship between energy and average particle size. Walker's model (n = 2.047 determined by fractal theory) had the best fitting effect.


Assuntos
Resíduo Eletrônico , Metais , Reciclagem
7.
Chemosphere ; 242: 125078, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31704520

RESUMO

The widespread use of tetrabromobisphenol A (TBBPA) in industries has resulted in its frequent detection in environmental matrices, and the mechanisms of its associated hazards need further investigation. In this study, the nematode Caenorhabditis elegans (C. elegans) was exposed to environmentally relevant concentrations of TBBPA (0, 0.1, 1, 10, 100, 200 µg/L) to determine its effects. At TBBPA concentrations above 1 µg/L, the number of head thrashes, as the most sensitive physiological indicator, decreased significantly. Using the Illumina HiSeq™ 2000 sequencer, differentially expressed genes (DEGs) were determined, and 52 were down regulated and 105 were up regulated in the 200 µg/L TBBPA treatment group versus the control group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database analysis demonstrated that dorso-ventral axis formation is related to neurotoxicity; metabolism of xenobiotics by Cytochrome P450 (CYP450) and glutathione-S-transferase (GST) was found to be the vital metabolic mechanisms and were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). GST was ascribed to the augmentation because mutations in cyp-13A7 were constrained under TBBPA exposure. Additionally, oxidative stress indicators accumulated in a dose-dependent relationship. These results will help understand the molecular basis for TBBPA-induced toxicity in C. elegans and open novel avenues for facilitating the exploration of more efficient strategies against TBBPA toxicity.

8.
Org Lett ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710499

RESUMO

The efficient synthetic route was disclosed to prepare optically active triarylborane-based [5]helicenes, 7B-PhHC and 7B5N-PhHC. Their emission wavelengths are tunable by both the chemical structure modification and the tuning of excited state charge transfer dynamics via selection of appropriate solvents or addition of external F-, enabling the full-color circularly polarized luminescence with moderate to good quantum yields (0.07-0.51) and high luminescence dissymmetry factors (glum > 5 × 10-3).

9.
J Synchrotron Radiat ; 26(Pt 6): 2024-2032, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31721747

RESUMO

Conventional imaging methods such as magnetic resonance imaging, computed tomography and digital subtraction angiography have limited temporospatial resolutions and shortcomings like invasive angiography, potential allergy to contrast agents, and image deformation, that restrict their application in high-resolution visualization of the structure of microvessels. In this study, through comparing synchrotron radiation (SR) absorption-contrast imaging to absorption phase-contrast imaging, it was found that SR-based phase-contrast imaging could provide more detailed ultra-high-pixel images of microvascular networks than absorption phase-contrast imaging. Simultaneously, SR-based phase-contrast imaging was used to perform high-quality, multi-dimensional and multi-scale imaging of rat brain angioarchitecture. With the aid of image post-processing, high-pixel-size two-dimensional virtual slices can be obtained without sectioning. The distribution of blood supply is in accordance with the results of traditional tissue staining. Three-dimensional anatomical maps of cerebral angioarchitecture can also be acquired. Functional partitions of regions of interest are reproduced in the reconstructed rat cerebral vascular networks. Imaging analysis of the same sample can also be displayed simultaneously in two- and three-dimensional views, which provides abundant anatomical information together with parenchyma and vessels. In conclusion, SR-based phase-contrast imaging holds great promise for visualizing microstructure of microvascular networks in two- and three-dimensional perspectives during the development of neurovascular diseases.

10.
J Intensive Care Med ; : 885066619887333, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722600

RESUMO

BACKGROUND: Diagnosing acute kidney injury (AKI) stage 3 in critically ill patients may help physicians in making treatment decisions. This diagnosis relies chiefly on urinary output and serum creatinine, which may be of limited value. This study aimed to explore the diagnostic performance of renal resistive index (RRI) and semiquantitative power Doppler ultrasound (PDU) scores in predicting AKI stage 3 in patients with sepsis or cardiac failure. METHODS: This study is a prospective observational study that included 83 patients (40 with sepsis and 43 with cardiac failure). Renal resistive index and semiquantitative PDU scores were measured within 6 hours following admission to the intensive care unit. Acute kidney injury was defined according to the criteria set by Kidney Disease Improving Global Outcomes. RESULTS: The predictive values of RRI (area under the curve [AUC] = 0.772, 95% confidence interval [CI] = 0.658-0.886) and PDU score (AUC = 0.780, 95% CI = 0.667-0.892) were similar in all patients. Power Doppler ultrasound score (AUC = 0.910, 95% CI = 0.815-1.000) could effectively predict AKI stage 3 in the cardiac failure subgroup, and the optimal cutoff for this parameter was ≤ 1 (sensitivity = 87.5%, specificity = 92.6%, Youden index = 0.801, accuracy in our population = 90.7%). However, PDU scores (AUC = 0.620, 95% CI = 0.425-0.814) could not predict AKI stage 3 in the sepsis subgroup. The predictive values of RRI for AKI stage 3 in the cardiac failure (AUC = 0.820, 95% CI = 0.666-0.974) and sepsis (AUC = 0.724, 95% CI = 0.538-0.910) subgroups were similar. CONCLUSIONS: Power Doppler ultrasound scores could effectively predict AKI stage 3 in patients with cardiac failure but not in patients with sepsis. Renal resistive index is a poor predictor of AKI stage 3 in patients with sepsis or cardiac failure.

11.
Int J Mol Sci ; 20(22)2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698756

RESUMO

The cytoplasmic male sterility (CMS)/restorer-of-fertility system is an important tool to exploit heterosis during commercially hybrid seed production. The importance of long noncoding RNAs (lncRNAs) in plant development is recognized, but few analyses of lncRNAs during anther development of three-line hybrid cotton (CMS-D2 line A, maintainer line B, restorer-of-fertility line R) have been reported. Here, we performed transcriptome sequencing during anther development in three-line hybrid cotton. A total of 80,695 lncRNAs were identified, in which 43,347 and 44,739 lncRNAs were differentially expressed in A-B and A-R comparisons, respectively. These lncRNAs represent functional candidates involved in CMS and fertility restoration. GO analysis indicated that cellular hormone metabolic processes and oxidation-reduction reaction processes might be involved in CMS, and cellular component morphogenesis and small molecular biosynthetic processes might participate in fertility restoration. Additionally, 63 lncRNAs were identified as putative precursors of 35 miRNAs, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed a similar expression pattern to RNA-seq data. Furthermore, construction of lncRNA regulatory networks indicated that several miRNA-lncRNA-mRNA networks might be involved in CMS and fertility restoration. Our findings provide systematic identification of lncRNAs during anther development and lays a solid foundation for the regulatory mechanisms and utilization in hybrid cotton breeding.

12.
Cell Oncol (Dordr) ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701491

RESUMO

PURPOSE: Endocrine therapy is the most commonly used approach for the treatment of estrogen receptor (ERα)-positive breast cancer. The cure rate of patients with ERα-positive breast cancer is, however, limited due to the occurrence of endocrine resistance. Loss of ERα is one major mechanism for the occurrence of endocrine resistance. Recent studies have shown that pan-HDAC inhibitors may be effective in reversing endocrine resistance. However, the molecular mechanism underlying this reversal has remained largely unknown. Here we aimed to unravel this mechanism. METHODS: Endocrine resistant breast cancer cell lines were established through exposure to tamoxifen. mRNA expression was assessed by qRT-PCR and protein expression by Western blotting. The effect of HDAC3 inhibition on the viability of endocrine resistant breast cancer cells was evaluated using CCK-8 and colony forming assays. Immunohistochemistry was used to detect protein expression in primary breast cancer tissues. RESULTS: We found that in endocrine resistant breast cancer cells loss of ERα led to HDAC3 stabilization via decreased ERα-mediated caspase7 expression, resulting in reduced caspase7-mediated HDAC3 cleavage. We also found that the ERα-caspase7-HDAC3 axis determined the global H3K9 and H4K16 acetylation status, which was positively correlated with ERα expression. Finally, we found that inhibition of HDAC3 significantly decreased the viability of endocrine resistant breast cancer cells exhibiting ERα deficiency. The ERα-caspase7-HDAC3 axis was subsequently verified in primary endocrine resistant breast cancer samples. CONCLUSIONS: From our data we conclude that the ERα-caspase7-HDAC3 axis may play a role in promoting the proliferation of endocrine resistant breast cancer cells. HDAC3 may serve as a therapeutic target for (a subset of) endocrine resistant breast cancers exhibiting ERα loss.

13.
Neurosci Lett ; : 134596, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711976

RESUMO

The occipital lobe has been implicated in anxiety disorder, however, its contributions to anxiety in healthy adults remain less clear. We conducted a resting-state functional magnetic resonance imaging study to explore the relationship between the amplitude of low-frequency fluctuation (ALFF), functional connectivity (FC), and state anxiety level in the healthy population. First, the results showed that the ALFF of the left inferior occipital gyrus (IOG) was negatively correlated with state anxiety. Furthermore, state anxiety was positively correlated with the FC between the left IOG and the right medial superior frontal gyrus and right cerebellum 8 area and negatively correlated with the FC between the left IOG and the left superior parietal gyrus. These results indicate that the occipital lobe of healthy individuals is involved in processing of anxiety in part through a frontal-parietal network.

14.
Sci Total Environ ; 694: 133803, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756841

RESUMO

Bamboo forests are an important part of the forest ecosystem, which has strong carbon sequestration potential and plays an important role in the global carbon cycle. As a key parameter for simulating the carbon cycle using forest ecosystem models, the quality of leaf area index (LAI) data has a direct influence on the accuracy of modelling results. Here, we used the particle filter (PF) algorithm and PROSAIL model to assimilate MODIS LAI products, which were then used to drive a boreal ecosystem productivity simulator model to simulate the bamboo forest carbon cycle. The results showed that the relationship between the assimilated and observed LAI values was very significant, with an R2 of 0.95 and an RMSE of 0.28, greatly improving the precision of MODIS LAI products. The R2 values for the gross primary productivity (GPP), net ecosystem exchange (NEE), and total ecosystem respiration (TER) simulated by the assimilated LAI values and observed carbon fluxes were 0.65, 0.45 and 0.70, respectively, and the RMSE values were 1.10 g C m-2 day-1, 1.00 g C m-2 day-1 and 0.35 g C m-2 day-1, respectively. Compared with the results of the carbon cycle simulated by non-assimilated LAI, the R2 values of the GPP, NEE and TER values that were simulated by assimilated LAI increased by 27.5%, 45.2% and 6.1%, and the RMSE values decreased by 29.9%, 23.7% and 22.2%, respectively. Therefore, coupling the PF and PROSAIL models can greatly improve the simulation precision for the large-scale bamboo forest carbon cycle. This study laid the foundation for simulating the carbon cycle over a large-scale bamboo forest based on low-resolution data in the future.

15.
Pharmacol Res ; : 104559, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31759089

RESUMO

Our previous studies indicated that the G-protein-coupled bile acid receptor, Gpbar1 (TGR5), inhibits inflammation by inhibiting the NF-κB signalling pathway, eventually attenuating diabetic nephropathy (DN). Gentiopicroside (GPS), the main active secoiridoid glycoside of Gentiana manshurica Kitagawa, has been demonstrated to inhibit inflammation in various diseases via inhibiting the inflammatory signalling pathways. However, whether GPS inhibits the NF-κB signalling pathway by activating TGR5 and regulates the pathological progression of diabetic renal fibrosis requires further investigation. In this study, we found that GPS significantly reversed the downregulation of TGR5 and inhibited the overproduction of fibronectin (FN), transforming growth factor ß1 (TGF-ß1), intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion molecule-1 (VCAM-1) in glomerular mesangial cells (GMCs) exposed to high glucose (HG). Additionally, GPS prevented the phosphorylation and degradation of IκBα, and subsequently inhibited the activation of the NF-κB signalling pathway. Further investigation found that GPS enhanced the stabilization of IκBα by promoting the interaction of ß-arrestin2 with IκBα via TGR5 activation, which contributed to the inhibition of NF-κB signalling pathway. Importantly, the depletion of TGR5 blocked the inhibition of the NF-κB signalling pathway and reversed the downregulation of FN, ICAM-1, VCAM-1 and TGF-ß1 by GPS in HG-induced GMCs. Moreover, GPS increased the TGR5 protein levels and promoted the interaction between IκBα and ß-arrestin2, thereby inhibiting the reduction of IκBα and blocked NF-κB p65 nuclear translocation in the kidneys of STZ-induced diabetic mice. Collectively, these data suggested that GPS regulates the TGR5-ß-arrestin2-NF-κB signalling pathway to prevent inflammation in the kidneys of diabetic mice, and ultimately ameliorates the pathological progression of diabetic renal fibrosis.

16.
Biomed Pharmacother ; 121: 109552, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715370

RESUMO

Rhodiola rosea L., a worldwide botanical adaptogen, has been confirmed to possess protective effects of inflammatory injury for many diseases, including cardiovascular diseases, neurodegenerative diseases, diabetes, sepsis, and cancer. This paper is to review the recent clinical and experimental researches about the anti-inflammatory effects and the related mechanisms of Rhodiola rosea L. extracts, preparations, and the active compounds. From the collected information reviewed, this paper will provide the theoretical basis for its clinical application, and provide the evidences or guidance for future studies and medicinal exploitations of Rhodiola rosea L.

17.
Sci Total Environ ; 702: 135006, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31726351

RESUMO

Multi-walled carbon nanotubes (MWCNTs) modified nickel foams (MWCNTs-NF) were developed with an electrophoretic deposition methodology for microwave (MW) assisted catalysis and processing enhancement. A nickel foam (NF) was selected to serve the dual purpose both as the MW absorbing catalytic materials and the matrix for MWCNTs loading in order to maximize the recyclability of the catalysts. The effects of electrophoretic voltage and concentration of electrophoretic fluid on the morphology and deposition characteristics of MWCNTs on the NF matrix were investigated. It was found that the MWCNTs-NF composite material resulted in strong enhancement of MW absorptivity with synergistic heat-generating effects that were not observed when MWCNTs or NF was exposed to MW alone. The combination of NF and MWCNTs brought a catalytic total organic carbon removal efficiency of 97% in wastewater treatment, while that using bare MWCNTs and NF were only 65.2% and 79.3%, respectively. The coupling of NF with MWCNTs led to the formation of additional MW-absorbing channels and focal sites with strong MW absorptivity, which in turn gave rise to the synergistic MW heating effects. This research highlights the great prospect of the MW-assisted reaction enhancement using the MWCNTs-NF composite material as the catalyst in wastewater treatment and other similar engineering applications.

18.
J Agric Food Chem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31765135

RESUMO

A series of N-aryl-pyridine-4-ones derivatives were designed and synthesized by using maltol and antidesmone as lead compounds, and then their fungicidal/bactericidal activities and possible mechanism of action against Colletotrichum musae were explored. Most of these compounds exhibited significant fungicidal activity in vitro. Especially, compound 23 has more than 90% inhibitory activity against 9 plant pathogenic fungi at 50 µg mL-1, which is superior to azoxystrobin. Moreover, in vivo bioassay also demonstrated that compound 23 exhibited high-efficiency broad-spectrum antifungal activity and can effectively control postharvest diseases of mango. In addition, it was found that compounds 22 and 23 can also effectively control rice bacterial leaf blight in pot experiments, which was even more effective than zhongshengmycin. Preliminary mechanism studies revealed that compound 23 maybe cause cell membrane and mitochondria destruction. These findings indicate that compound 23 can be used to develop potential agrochemical fungicides and bactericides.

19.
Sci Total Environ ; : 134920, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31744693

RESUMO

Tetrabromobisphenol A (TBBPA), one of the most common brominated flame retardants, has been associated with immunotoxicity, neurotoxicity, and reproductive toxicity. However, little attention has been focused on understanding the trans-generational effects of TBBPA. The present study used the Caenorhabditis elegans (C. elegans) animal model to evaluate the trans-generational effects of neurotoxicity induced by environmentally relevant concentrations of TBBPA (0, 0.1, 1, 10, 100, and 1000 µg/L). Multiple indicators including physiological effects (body length, brood size, head thrashes, body bends, and crawling trajectory), degree of neuronal damage (dopamine, GABAergic, and glutamatergic neurons), oxidative stress-related biochemical indicators (superoxide dismutase [SOD] activity, catalase [CAT] enzyme, malondialdehyde [MDA] production, and reactive oxygen species [ROS] accumulation), and stress-related gene expressions have been evaluated in the exposed parental C. elegans generation (G1) and their progeny (G2) under TBBPA-free conditions. The results showed that TBBPA exposure induced adverse effects on physiological endpoints, among which body bends and head thrashes were the most sensitive ones, detected above 1 µg/L in G1 and 100 µg/L in G2 nematodes, respectively. After contaminant exposure, the three neurons revealed damage related to neurobehavioral endpoints, with no hereditary effects in the progeny. The oxidative stress-related biochemical endpoints demonstrated that when the exposure concentrations were above 1 µg/L in maternal worms, impairment can be detected in both generations, but the progeny recovered at low toxicity concentration (1-100 µg/L). The integrated target gene expression profiles were clearly altered in G1 and G2 worms at concentrations between 1 and 1000 µg/L, and a more significant difference existed in two generations of nematodes at low levels (1-10 µg/L) of TBBPA. Studing trans-generational neurotoxicity and the underlying mechanism can generate a precise evaluation of the environmental risk of TBBPA.

20.
Sci Signal ; 12(608)2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744929

RESUMO

The stromal interaction molecule 1 (STIM1) has two important functions, Ca2+ sensing within the endoplasmic reticulum and activation of the store-operated Ca2+ channel Orai1, enabling plasma-membrane Ca2+ influx. We combined molecular dynamics (MD) simulations with live-cell recordings and determined the sequential Ca2+-dependent conformations of the luminal STIM1 domain upon activation. Furthermore, we identified the residues within the canonical and noncanonical EF-hand domains that can bind to multiple Ca2+ ions. In MD simulations, a single Ca2+ ion was sufficient to stabilize the luminal STIM1 complex. Ca2+ store depletion destabilized the two EF hands, triggering disassembly of the hydrophobic cleft that they form together with the stable SAM domain. Point mutations associated with tubular aggregate myopathy or cancer that targeted the canonical EF hand, and the hydrophobic cleft yielded constitutively clustered STIM1, which was associated with activation of Ca2+ entry through Orai1 channels. On the basis of our results, we present a model of STIM1 Ca2+ binding and refine the currently known initial steps of STIM1 activation on a molecular level.

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