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1.
Med Image Anal ; 61: 101656, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32062154

RESUMO

Brain imaging genetics becomes an important research topic since it can reveal complex associations between genetic factors and the structures or functions of the human brain. Sparse canonical correlation analysis (SCCA) is a popular bi-multivariate association identification method. To mine the complex genetic basis of brain imaging phenotypes, there arise many SCCA methods with a variety of norms for incorporating different structures of interest. They often use the group lasso penalty, the fused lasso or the graph/network guided fused lasso ones. However, the group lasso methods have limited capability because of the incomplete or unavailable prior knowledge in real applications. The fused lasso and graph/network guided methods are sensitive to the sign of the sample correlation which may be incorrectly estimated. In this paper, we introduce two new penalties to improve the fused lasso and the graph/network guided lasso penalties in structured sparse learning. We impose both penalties to the SCCA model and propose an optimization algorithm to solve it. The proposed SCCA method has a strong upper bound of grouping effects for both positively and negatively highly correlated variables. We show that, on both synthetic and real neuroimaging genetics data, the proposed SCCA method performs better than or equally to the conventional methods using fused lasso or graph/network guided fused lasso. In particular, the proposed method identifies higher canonical correlation coefficients and captures clearer canonical weight patterns, demonstrating its promising capability in revealing biologically meaningful imaging genetic associations.

2.
Environ Sci Technol ; 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32062963

RESUMO

To achieve low regeneration energy consumption and viscosity, a novel amino functionalized ionic liquid of [TEPAH][2-MI] combined with organic solvents has been proposed for CO2 capture in this work. The results demonstrated that the absorption loading of [TEPAH][2-MI]/NPA/EG was 1.72 mol·mol-1 (28 wt%, 257 g·L-1), which was much higher than that of MEA/water, and the regeneration efficiency was maintained at 90.7% after the 5th regeneration cycle. The viscosities of the solution were only 3.66 and 7.65 mPa·s before and after absorption, which were significantly lower than that of traditional non-aqueous absorbents. The reaction mechanism investigated via 13C NMR and quantum calculations were summarized that CO2 firstly reacted with the amino group of [TEPAH]+ to form the carbamates through the zwitterion formation and protonation process, while CO2 reacted with the N atom of [2-MI]- to directly form carbamate. Then some of them further reacted with NPA and EG to form the carbonates. Moreover, Nπ and Nτ tautomers of [TEPAH][2-MI] could convert into each other continuously when CO2 was absorbed. During CO2 desorption, the carbamates and carbonates reacted with AFILH+ to decompose and released CO2 directly.

3.
Int J Infect Dis ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32004687

RESUMO

OBJECTIVE: To assess the immune effect of different types of hepatitis B vaccine (HepB) booster doses 2 to 32 years after primary immunization, explore the influencing factors, and offer guidance regarding the necessity and timing of boosters. METHODS: In total, 1163 participants who were born from 1986 to 2015, received the HepB full-course primary vaccination, were hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) negative, and had hepatitis B surface antibody (anti-HBs) <10 mIU/mL were enrolled. Individuals were randomly divided into two groups and received a booster dose of HepB. Venous blood samples were collected 30 days later and tested for anti-HBs. RESULTS: In total, 595 and 568 individuals received a single dose of HepB (CHO) and HepB (SC), respectively. Venous blood samples were obtained from 1079 vaccinees (CHO: 554, SC: 525). The seroconversion rates were 93.68% (519/554) and 86.67% (455/525) (p < 0.05), with geometric mean concentrations (GMCs) of 426.58 mIU/ml and 223.87 mIU/ml, respectively. This result indicated that BMI, smoking status, vaccine types of booster and prebooster anti-HBs concentration significantly influenced anti-HBs levels. Only BMI, prebooster anti-HBs concentrations and booster types were different between the anti-HBs positive and negative groups. CONCLUSIONS: Participants boostered with HepB (CHO) had a relatively higher seroconversion rate than those boostered with HepB (SC). The high seroconversion rates in the two groups suggested that the subjects remained protected despite low circulating antibodies, so there is currently no urgent need for booster immunization. Factors including BMI ≥ 25 and prebooster anti-HBs concentration < 2.5 mIU/mL, which contributed to lower responses to a booster dose, might indicate a greater risk of breakthrough infection.

4.
Inorg Chem ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32045227

RESUMO

Colorimetric assays have drawn increasing research interest with respect to the quantitative detection of hydrogen peroxide (H2O2) based on artificial enzymes because of their advantages with respect to natural enzymes, including design flexibility, low cost, and high stability. Regardless, the majority of the artificial enzymes exhibit low affinity to H2O2 with large Michaelis-Menten constants (Km). This indicates that the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to blue-colored oxTMB requires a high H2O2 concentration, hindering the sensitivity of the colorimetric assay. To address this problem, novel reduced Co3O4 nanoparticles (R-Co3O4) have been synthesized in this study via a step-by-step procedure using ZIF-67 as the precursor. R-Co3O4 exhibits a considerably enhanced peroxidase-like activity when compared with that exhibited by pristine Co3O4 (P-Co3O4). The catalytic process in the case of R-Co3O4 occurs in accordance with the typical Michaelis-Menten equation, and the affinity of R-Co3O4 to H2O2 is apparently higher than that of P-Co3O4. Furthermore, the density functional theory calculations revealed that the introduction of oxygen vacancies to R-Co3O4 enhances its H2O2 adsorption ability and facilitates the decomposition of H2O2 to produce ·OH radicals, resulting in improved peroxidase-like activity. A simple and convenient colorimetric assay has been established based on the excellent peroxidase-like activity of R-Co3O4 for detecting H2O2 in concentrations of 1-30 µM with a detection limit of 4.3 × 10-7 mol/L (S/N = 3). Furthermore, the R-Co3O4-based colorimetric method was successfully applied to glucose detection in human serum samples, demonstrating its potential for application in complex biological systems.

5.
Life Sci ; : 117402, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32035930

RESUMO

AIMS: Gastric cancer (GC) is one of the most common malignant tumors in the world. Anti-angiogenic therapy is a useful strategy for the treatment of advanced GC. This study was aimed to systemically compare the anti-angiogenesis, anti-cancer efficacy, as well as the safety of four known anti-angiogenic drugs, namely ramucirumab, apatinib, regorafenib and cabozantinib. MAIN METHODS: Anti-angiogenic effect was evaluated for the intersegmental vessels (ISVs) and subintestinal veins (SIVs) formation in the Tg (fli-1: EGFP) zebrafish embryos. Anti-cancer efficacy was tested for the in vivo cell proliferation in cell line derived tumor xenograft (CDX) model based on Tg (fli-1: EGFP) zebrafish embryos. KEY FINDINGS: All four drugs exhibited anti-angiogenic abilities and tumor inhibition effects in fli-1: EGFP transgenic zebrafish. Using zebrafish xenografted model, we found that effectiveness of ramucirumab in anti-GC-proliferation is better than apatinib, regorafenib and cabozantinib. The combination of anti-angiogenic drugs and cisplatin showed no significant benefit in tumors. Meanwhile, toxicity assay showed that all tested anti-angiogenic drugs could cause cardiovascular-related side effects. The therapeutic index (LD50/ED50) of cabozantinib is higher than apatinib and regorafenib, suggesting a potential as an anti-GC drug. SIGNIFICANCE: The comparison of GC-related anti-angiogenic drugs was first reported. It was found that cabozantinib had a potential as an anti-GC drug. Zebrafish model was an ideal animal model for the research of anti-angiogenic behaviors.

6.
JAMA Cardiol ; 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995119

RESUMO

Importance: Accurate prediction of risk of death or hospitalizations in patients with heart failure (HF) may allow physicians to explore how more accurate decisions regarding appropriateness and timing of disease-modifying treatments, advanced therapies, or the need for end-of-life care can be made. Objective: To develop and validate a prognostic model for patients with HF. Design, Setting, and Participants: Multivariable analyses were performed in a stepwise fashion. Harrell C statistic was used to assess the discriminative ability. The derivation cohort was Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure trial (PARADIGM-HF) participants. The models were validated using the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure Trial (ATMOSPHERE) study and in the Swedish Heart Failure Registry (SwedeHF). A total of 8399 participants enrolled in PARADIGM-HF. Data were analyzed between June 2016 and June 2018. Main Outcomes and Measures: Cardiovascular death, all-cause mortality, and the composite of cardiovascular death or HF hospitalization at both 1 and 2 years. Results: Complete baseline clinical data were available for 8011 patients in PARADIGM-HF. The mean (SD) age of participants was 64 (11.4) years, 78.2% were men (n = 6567 of 8011), and 70.6% were New York Heart Association class II (n = 5919 of 8011). During a mean follow-up of 27 months, 1546 patients died, and 2031 had a cardiovascular death or HF hospitalization. The common variables were: male sex, race/ethnicity (black or Asian), region (Central Europe or Latin America), HF duration of more than 5 years, New York Heart Association class III/ IV, left ventricular ejection fraction, diabetes mellitus, ß-blocker use at baseline, and allocation to sacubitril/valsartan. Ranked by χ2, N-terminal pro brain natriuretic peptide was the single most powerful independent predictor of each outcome. The C statistic at 1 and 2 years was 0.74 (95% CI, 0.71-0.76) and 0.71 (95% CI, 0.70-0.73) for the primary composite end point, 0.73 (95% CI, 0.71-0.75) and 0.71 (95% CI, 0.69-0.73) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.67-0.74) for all-cause death, respectively. When validated in ATMOSPHERE, the C statistic at 1 and 2 years was 0.71 (95% CI, 0.69-0.72) and 0.70 (95% CI, 0.68-0.71) for the primary composite end point, 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.69-0.72) for cardiovascular death, and 0.71 (95% CI, 0.69-0.74) and 0.70 (95% CI, 0.68-0.72) for all-cause death, respectively. An online calculator was created to allow calculation of an individual's risk (http://www.predict-hf.com). Conclusions and Relevance: Predictive models performed well and were developed and externally validated in large cohorts of geographically representative patients, comprehensively characterized with clinical and laboratory data including natriuretic peptides, who were receiving contemporary evidence-based treatment.

7.
Respir Res ; 21(1): 1, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898493

RESUMO

OBJECTIVE: To observe the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for pulmonary alveolar proteinosis (PAP). MATERIALS AND METHODS: A total of 55 patients with PAP were screened at Shanghai Pulmonary Hospital between May 2014 and May 2018. Among these, 42 were diagnosed with idiopathic PAP, 24 were included in this study, 20 were treated for 6 months, and 17 were followed up for additional 6 months. All patients received a subcutaneous injection of 75µg/d GM-CSF qd for 1 month. The therapeutic dose was adjusted according to the changes in the lesions of chest CT. If the lesions were absorbed, subcutaneous injections of 75µg/d GM- CSF qd and 75µg/d GM-CSF qod were given for 2 and 3 months, otherwise, the dose was increased to 150µg/d GM-CSF qd and 150µg/d qod for 2 and 3 months, respectively. All cases were treated once a day in the first 3 months and once every other day in the last 3 months. The total course of treatment was 6 months. After withdrawal, the patients were followed up for another 6 months. The deadline of follow up was September 30, 2019. RESULTS: Twenty patients completed the treatment and efficacy evaluation. One patient was completely cured, 16 cases improved, three cases were noneffective. After 1-month evaluation, 12 patients received an increased dose (150µg) from the second month of treatment. Seventeen patients completed the 12-month follow-up, among which fourteen improved. CT showed the lesions were slightly increased in three cases. Economic burden was the following: RMB 7324-15,190 Yuan were required for the 6-month treatment course, which is significantly lower compared to other treatment methods. CONCLUSION: Subcutaneous injection of rhGM-CSF at low dose (75µg-150µg /d) is effective treatment for patients with idiopathic PAP. TRIAL REGISTRATION: NCT01983657. Registered 16 April 2013.

8.
Cell Rep ; 30(1): 25-36.e6, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31914391

RESUMO

Known as a histone H3K9 methyltransferase, SETDB1 is essential for embryonic development and pluripotent inner cell mass (ICM) establishment. However, its function in pluripotency regulation remains elusive. In this study, we find that under the "ground state" of pluripotency with two inhibitors (2i) of the MEK and GSK3 pathways, Setdb1-knockout fails to induce trophectoderm (TE) differentiation as in serum/LIF (SL), indicating that TE fate restriction is not the direct target of SETDB1. In both conditions, Setdb1-knockout activates a group of genes targeted by SETDB1-mediated H3K9 methylation, including Dux. Notably, Dux is indispensable for the reactivation of 2C-like state genes upon Setdb1 deficiency, delineating the mechanistic role of SETDB1 in totipotency restriction. Furthermore, Setdb1-null ESCs maintain pluripotent marker (e.g., Nanog) expression in the 2i condition. This "ground state" Setdb1-null population undergoes rapid cell death by activating Ripk3 and, subsequently, RIPK1/RIPK3-dependent necroptosis. These results reveal the essential role of Setdb1 between totipotency and pluripotency transition.

9.
J Behav Med ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919776

RESUMO

The original version of this article unfortunately contained a typo in the second author surname. The author surname was incorrectly listed as Borhneimer. The correct name should be Bornheimer.

11.
BMC Plant Biol ; 20(1): 28, 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31955709

RESUMO

In the original publication of this article [1], the authors pointed out the Fig. 4b was same with Fig. 4c. The correct Fig. 4b should be below.

12.
Nucleic Acids Res ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956913

RESUMO

The transcription factor Six1 is essential for induction of sensory cell fate and formation of auditory sensory epithelium, but how it activates gene expression programs to generate distinct cell-types remains unknown. Here, we perform genome-wide characterization of Six1 binding at different stages of auditory sensory epithelium development and find that Six1-binding to cis-regulatory elements changes dramatically at cell-state transitions. Intriguingly, Six1 pre-occupies enhancers of cell-type-specific regulators and effectors before their expression. We demonstrate in-vivo cell-type-specific activity of Six1-bound novel enhancers of Pbx1, Fgf8, Dusp6, Vangl2, the hair-cell master regulator Atoh1 and a cascade of Atoh1's downstream factors, including Pou4f3 and Gfi1. A subset of Six1-bound sites carry consensus-sequences for its downstream factors, including Atoh1, Gfi1, Pou4f3, Gata3 and Pbx1, all of which physically interact with Six1. Motif analysis identifies RFX/X-box as one of the most significantly enriched motifs in Six1-bound sites, and we demonstrate that Six1-RFX proteins cooperatively regulate gene expression through binding to SIX:RFX-motifs. Six1 targets a wide range of hair-bundle regulators and late Six1 deletion disrupts hair-bundle polarity. This study provides a mechanistic understanding of how Six1 cooperates with distinct cofactors in feedforward loops to control lineage-specific gene expression programs during progressive differentiation of the auditory sensory epithelium.

13.
Int J Infect Dis ; 92: 97-104, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945493

RESUMO

Long non-coding RNAs (lncRNAs) are defined as a class of RNA molecules with a length of more than 200 nucleotides that are not translated into protein, and are known to participate in a variety of biological processes. They have recently been implicated as having roles in viral infections, and several research groups have identified that complex interactions exist between lncRNAs and the progression of human immunodeficiency virus (HIV) infection. lncRNAs derived from both the human host and HIV itself are emerging as key regulators of various cellular functions, playing crucial roles in virus-host interactions and viral pathogenesis. This review provides a brief discussion of the roles and associated mechanisms of lncRNAs in HIV infection. Moreover, due to the continued lack of effective HIV vaccines or treatments, we provide an insight into the complex interplay between lncRNAs and HIV and suggest innovative therapeutic strategies for HIV/acquired immunodeficiency syndrome (AIDS). The available data on lncRNAs that have been associated with HIV infection and their potential applications for the treatment of HIV are summarized for the first time, providing a new perspective for the future development of therapeutic strategies.

14.
Drug Test Anal ; 12(1): 109-118, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31668004

RESUMO

Erythropoietins (EPOs) are substances listed in S2 of the World Anti-Doping Agency (WADA) Prohibited List and are used commonly by athletes to increase endurance performance. According to the current WADA Technical Documents, sarcosyl-polyacrylamide gel electrophoresis (SAR-PAGE) followed by western blotting to differentiate erythropoietins based on their molecular weights is the only method that can be used for both screening and confirmation of all types of erythropoietins. The efficiency of immunopurification and protein transfer is crucial for ensuring the selectivity and sensitivity of erythropoietin detection. Several comparisons and optimization of the SAR-PAGE tests were conducted in this study. We optimized the first blotting conditions and then compared different immunopurification methods based on their selectivity, repeatability, and sensitivity for both urine and blood analysis. Additionally, rapid procedures for both urine and blood analysis were established and compared. The two-step procedure at 1.0 mA/cm2 for 60 min followed by 1.56 mA/cm2 for 20 min increased the blotting efficiency compared with the commonly used constant current approach. Comparison of immunopurification revealed no significant difference in selectivity and sensitivity between the different methods. For other factors, such as operation complexity, time and cost, a StemCell® purification kit followed by single blotting and magnetic beads followed by double blotting are recommended for urine screening and confirmation, respectively. While magnetic beads and a MAIIA® kit followed by double blotting are recommended for both screening and confirmation of blood samples, respectively. To ensure high sensitivity and selectivity, double blotting is recommended for a rapid procedure for both urine and blood analysis.

15.
Chemistry ; 26(6): 1396-1405, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31737953

RESUMO

The dissociation of hierarchically formed dimeric triple lithium bridged triscatecholate titanium(IV) helicates with hydrocarbyl esters as side groups is systematically investigated in DMSO. Primary alkyl, alkenyl, alkynyl as well as benzyl esters are studied in order to minimize steric effects close to the helicate core. The 1 H NMR dimerization constants for the monomer-dimer equilibrium show some solvent dependent influence of the side chains on the dimer stability. In the dimer, the ability of the hydrocarbyl ester groups to aggregate minimizes their contacts with the solvent molecules. Due to this, most solvophobic alkyl groups show the highest dimerization tendency followed by alkenyls, alkynyls and finally benzyls. Furthermore, trends within the different groups of compounds can be observed. For example, the dimer is destabilized by internal double or triple bonds due to π-π repulsion. A strong indication for solvent supported London dispersion interaction between the ester side groups is found by observation of an even/odd alternation of dimerization constants within the series of n-alkyls, n-Ω-alkenyls or n-Ω-alkynyls. This corresponds to the interaction of the parent hydrocarbons, as documented by an even/odd melting point alternation.

16.
Int J Biochem Cell Biol ; 118: 105653, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743794

RESUMO

Hypertension is one of the main risks causing cardiovascular diseases. Long noncoding RNAs (lncRNAs) play a critical role in many physiological and pathological conditions. However, their role in hypertension is still unclear. In this study, 460 lncRNAs and 522 mRNA were identified to have different expressions in the thoracic aortas of spontaneously hypertensive rats compared with normotensive Wistar-Kyoto rats through next-generation sequencing. Several randomly selected lncRNAs including NONRATT011842 were validated by qRT-PCR and their potential functions were predicted by co-expression analysis with the help of bioinformatics. Moreover, this study focused on the function of lncRNA NONRATT011842 in the vascular smooth muscle cells (VSMCs) during hypertension and confirmed that NONRATT011842 could interact with PABPC1 to regulate the functions of VSMCs. Therefore, the intervention or utilization of certain lncRNAs could be a new biomarker for the diagnosis and prevention of hypertension.

17.
Mol Cancer Ther ; 19(1): 147-156, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31582532

RESUMO

Receptor tyrosine kinase inhibitors have shown clinical benefit in clear cell renal cell carcinoma (ccRCC), but novel therapeutic strategies are needed. The angiopoietin/Tie2 and MET pathways have been implicated in tumor angiogenesis, metastases, and macrophage infiltration. In our study, we used trebananib, an angiopoietin 1/2 inhibitor, and a novel small-molecule MET kinase inhibitor in patient-derived xenograft (PDX) models of ccRCC. Our goal was to assess the ability of these compounds to alter the status of tumor-infiltrating macrophages, inhibit tumor growth and metastases, and prolong survival. Seven-week-old SCID mice were implanted subcutaneously or orthotopically with human ccRCC models. One month postimplantation, mice were treated with angiopoietin 1/2 inhibitor trebananib (AMG 386), MET kinase inhibitor, or combination. In our metastatic ccRCC PDX model, RP-R-02LM, trebananib alone, and in combination with a MET kinase inhibitor, significantly reduced lung metastases and M2 macrophage infiltration (P = 0.0075 and P = 0.0205, respectively). Survival studies revealed that treatment of the orthotopically implanted RP-R-02LM tumors yielded a significant increase in survival in both trebananib and combination groups. In addition, resection of the subcutaneously implanted primary tumor allowed for a significant survival advantage to the combination group compared with vehicle and both single-agent groups. Our results show that the combination of trebananib with a MET kinase inhibitor significantly inhibits the spread of metastases, reduces infiltrating M2-type macrophages, and prolongs survival in our highly metastatic ccRCC PDX model, suggesting a potential use for this combination therapy in treating patients with ccRCC.

18.
Neuroinformatics ; 18(1): 43-57, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31016571

RESUMO

Fractional amplitude of low-frequency fluctuation (fALFF) has been widely used for resting-state functional magnetic resonance imaging (rs-fMRI) based schizophrenia (SZ) diagnosis. However, previous studies usually measure the fALFF within low-frequency fluctuation (from 0.01 to 0.08Hz), which cannot fully cover the complex neural activity pattern in the resting-state brain. In addition, existing studies usually ignore the fact that each specific frequency band can delineate the unique spontaneous fluctuations of neural activities in the brain. Accordingly, in this paper, we propose a novel hierarchical structured sparse learning method to sufficiently utilize the specificity and complementary structure information across four different frequency bands (from 0.01Hz to 0.25Hz) for SZ diagnosis. The proposed method can help preserve the partial group structures among multiple frequency bands and the specific characters in each frequency band. We further develop an efficient optimization algorithm to solve the proposed objective function. We validate the efficacy of our proposed method on a real SZ dataset. Also, to demonstrate the generality of the method, we apply our proposed method on a subset of Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Experimental results on both datasets demonstrate that our proposed method achieves promising performance in brain disease classification, compared with several state-of-the-art methods.

19.
Nucleic Acids Res ; 48(2): 879-894, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31777931

RESUMO

An important event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In both invertebrates and vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date the mechanisms that activate the Z-decay pathway in mammalian early embryos have not been investigated. Here, we identify murine maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic expression of terminal uridylyltransferases TUT4 and TUT7 and mRNA 3'-oligouridylation direct Z-decay. Components of the M-decay pathway, including BTG4 and the CCR4-NOT deadenylase, continue to function in Z-decay but require reinforcement from the zygotic factors for timely removal of maternal mRNAs. A long 3'-UTR and active translation confer resistance of Z-decay transcripts to M-decay during oocyte meiotic maturation. The Z-decay pathway is required for mouse embryo development beyond the four-cell stage and contributes to the developmental competence of preimplantation embryos.

20.
Bioprocess Biosyst Eng ; 43(1): 153-167, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31549306

RESUMO

Heavy metal resistant bacteria are of great interest because of their potential use in bioremediation. Understanding the survival and adaptive strategies of these bacteria under heavy metal stress is important for better utilization of these bacteria in remediation. The objective of this study was to investigate the role of bacterial extracellular polymeric substance (EPS) in detoxifying against different heavy metals in Bacillus sp. S3, a new hyper antimony-oxidizing bacterium previously isolated from contaminated mine soils. The results showed that Bacillus sp. S3 is a multi-metal resistant bacterial strain, especially to Sb(III), Cu(II) and Cr(VI). Toxic Cd(II), Cr(VI) and Cu(II) could stimulate the secretion of EPS in Bacillus sp. S3, significantly enhancing the adsorption and detoxification capacity of heavy metals. Both Fourier transform infrared spectroscopy (FTIR) and three-dimensional excitation-emission matrix (3D-EEM) analysis further confirmed that proteins were the main compounds of EPS for metal binding. In contrast, the EPS production was not induced under Sb(III) stress. Furthermore, the TEM-EDX micrograph showed that Bacillus sp. S3 strain preferentially transported the Sb(III) to the inside of the cell rather than adsorbed it on the extracellular surface, indicating intracellular detoxification rather than extracellular EPS precipitation played an important role in microbial resistance towards Sb(III). Together, our study suggests that the toxicity response of EPS to heavy metals is associated with difference in EPS properties, metal types and corresponding environmental conditions, which is likely to contribute to microbial-mediated remediation.

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