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1.
Cancer Lett ; 511: 26-35, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33933552

RESUMO

A20 is a prototypical anti-inflammatory molecule that is linked to multiple human diseases, including cancers. The role of A20 as a tumor suppressor was first discovered in B cell lymphomas. Subsequent studies revealed the dual roles of A20 in solid cancers. This review focuses on the roles of A20 in different cancer types to demonstrate that the effects of A20 are cancer type-dependent. A20 plays antitumor roles in colorectal carcinomas and hepatocellular carcinomas, whereas A20 acts as an oncogene in breast cancers, gastric cancers and melanomas. Moreover, the roles of A20 in the setting of glioma therapy are context-dependent. The action mechanisms of A20 in different types of cancer are summarized. Additionally, the role of A20 in antitumor immunity is discussed. Furthermore, some open questions in this rapidly advancing field are proposed. Exploration of the actions and molecular mechanisms of A20 in cancer paves the way for the application of A20-targeting approaches in future cancer therapy.

2.
Proc Natl Acad Sci U S A ; 118(16)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33846262

RESUMO

Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. O. Rock, J. E. Cronan, Jr, Microbiol. Rev. 57, 522-542 (1993)]. Carrier proteins in particular play an essential role in shuttling substrates between appropriate enzymes in metabolic pathways. Although hypothesized [E. Ploskon et al., Chem. Biol. 17, 776-785 (2010)], allosteric regulation of substrate delivery has never before been demonstrated for any acyl carrier protein (ACP)-dependent pathway. Studying these mechanisms has remained challenging due to the transient and dynamic nature of protein-protein interactions, the vast diversity of substrates, and substrate instability [K. Finzel, D. J. Lee, M. D. Burkart, ChemBioChem 16, 528-547 (2015)]. Here we demonstrate a unique communication mechanism between the ACP and partner enzymes using solution NMR spectroscopy and molecular dynamics to elucidate allostery that is dependent on fatty acid chain length. We demonstrate that partner enzymes can allosterically distinguish between chain lengths via protein-protein interactions as structural features of substrate sequestration are translated from within the ACP four-helical bundle to the protein surface, without the need for stochastic chain flipping. These results illuminate details of cargo communication by the ACP that can serve as a foundation for engineering carrier protein-dependent pathways for specific, desired products.

3.
J Investig Med ; 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906902

RESUMO

To investigate the effort of mitochondrial calcium transport and calcium-induced membrane permeability transition in alleviating atherosclerosis. The experimental mice were divided into three groups: the control group (C57BL/6 mice with normal diet), the atherosclerosis group (apolipoprotein E-deficient (ApoE-/-) mice with high-fat diet) and the mitochondrial targeting agent group (ApoE-/- mouse with high-fat diet). The mean fluorescence intensity of Ca2+ in the atherosclerosis group is significantly higher than control group and mitochondrial targeting agent group. But the mean fluorescence intensity of Ca2+-ATPase is lower than other groups. The macrophage recruitment (F4/80 positive area) and the expression of tumor necrosis factor alpha, interleukin-6, pyrin domain containing protein 3, intercellular cell adhesion molecule-1, p38 mitogen-activated protein kinase and Jun kinase 1/2 phosphorylation in the atherosclerosis group are higher that other groups. Treatment with mitochondrial targeting agents reduced the levels of elevated cyt C and cleaved caspase-3 in atherosclerotic mice (p<0.05). Mitochondrial targeting agents interfere with mitochondrial calcium transport and calcium-induced membrane permeability transition, inhibit MAPK/JNK pathway activation, inhibit foam cell formation and alleviate the process of atherosclerosis.

4.
Adv Exp Med Biol ; 1280: 39-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791973

RESUMO

Shotgun lipidomics is an analytical approach for large-scale and systematic analysis of the composition, structure, and quantity of cellular lipids directly from lipid extracts of biological samples by mass spectrometry. This approach possesses advantages of high throughput and quantitative accuracy, especially in absolute quantification. As cancer research deepens at the level of quantitative biology and metabolomics, the demand for lipidomics approaches such as shotgun lipidomics is becoming greater. In this chapter, the principles, approaches, and some applications of shotgun lipidomics for cancer research are overviewed.


Assuntos
Lipidômica , Neoplasias , Lipídeos , Espectrometria de Massas , Metabolômica , Pesquisa
5.
Artigo em Inglês | MEDLINE | ID: mdl-33814906

RESUMO

Background: We aimed to investigate the association between red cell index (RCI) and the severity of Chronic Obstructive Pulmonary Disease (COPD), and compare predictive value of RCI, neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) for the severity of COPD. Methods: A total of 207 participants were recruited (100 COPD patients and 107 healthy controls). COPD patients were divided into two groups according to the optimal cut-off value of RCI determined by the receiver operating characteristic (ROC) curve. Pearson's correlation test, logistic regression analysis and other tests were performed. Results: Compared with low RCI group, the forced expiration volume in 1 second (FEV1) and FEV1 in percent of the predicted value (FEV1%) in high RCI group were lower (p = 0.016, p = 0.001). There was a negative correlation between RCI and FEV1% (r = -0.302, p = 0.004), while no correlation between FEV1% and NLR as well as PLR were found. RCI showed higher predictive value than NLR and PLR for predicting Global Initiative for Chronic Obstructive Lung Disease classification (GOLD), with a cut-off value of 1.75 and area under the curve (AUC) of 0.729 (p = 0.001). Multivariate logistic regression analysis proved that RCI was an independent factor for lung function in COPD patients (odds ratio [OR] = 4.27, 95% CI: 1.57-11.63, p = 0.004). Conclusion: RCI is a novel biomarker that can better assess pulmonary function and severity of COPD than NLR and PLR. Higher RCI is related to deterioration of pulmonary function.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33864264

RESUMO

BACKGROUND: Smoking is a major public health problem. However, its association with hypertensive disorders of pregnancy (HDP) is inconclusive. OBJECTIVE: To find the association between smoking during pregnancy and HDP. SEARCH STRATEGY: We searched PubMed, Ovid and Cochrane Library up to March, 2021, using terms including "smoking" and "hypertensive disorders of pregnancy". SELECTION CRITERIA: Observational studies that assessed the relationship between smoking during pregnancy and HDP were included. DATA COLLECTION AND ANALYSIS: Odds ratios (OR) and 95% confidence intervals (CI), and other necessary data were extracted. Stata16.0 MP was used to analyze statistics. MAIN RESULTS: A total of 13 studies were included. Meta-analysis revealed smoking during pregnancy was a protective factor for HDP (OR=0.78, 95%CI= [0.67,0.92]), gestational hypertension (GH: OR=0.74, 95%CI= [0.69,0.79]), and preeclampsia (PE: OR=0.65, 95%CI= [0.58,0.73]). Subgroup analysis showed smoking during pregnancy was a risk factor for HDP in Asia but a protective factor in Europe and North America. Neither quitting smoking before pregnancy nor during pregnancy had statistically association with HDP. CONCLUSION: This meta-analysis revealed smoking during pregnancy might prevent HDP, GH and PE. Smoking during pregnancy was a risk factor for HDP in Asia but a protective factor in Europe and North America.

7.
Lab Invest ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753880

RESUMO

Endometrial carcinoma is one of the most common malignancies in the female reproductive system. Interleukin-37 (IL-37) is a newly discovered anti-inflammatory factor belonging to the IL-1 family. IL-37 has five different isoforms, and IL-37b is the most biologically functional subtype. In recent years, the protective roles of IL-37 in different cancers, including lung and liver cancers, have been successively reported. IL-37 also plays an important role in some gynecological diseases such as endometriosis, adenomyosis, and cervical cancer. However, the role and mechanism of IL-37b, especially the mature form of IL-37b, in endometrial carcinoma have not been elucidated. The present study demonstrated that IL-37 protein was downregulated in endometrial carcinoma cells compared with the control endometrium. IL-37b did not affect the proliferation and colony-forming ability of endometrial cancer cells. A mature form of IL-37b (IL-37bΔ1-45) effectively suppressed the migration and invasion of endometrial cancer cells by decreasing the expression of matrix metalloproteinase 2 (MMP2) via Rac1/NF-κB signal pathway. However, it did not affect epithelial-mesenchymal transition (EMT) or filamentous actin (F-actin) depolymerization of endometrial cancer cells. IL-37bΔ1-45 attenuated tumor metastasis in a peritoneal metastatic xenograft model of endometrial cancer. To sum up, these results suggested IL-37b could be involved in the pathogenesis of endometrial carcinoma and provide a novel target for the diagnosis and treatment of endometrial carcinoma.

8.
AIDS Behav ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751315

RESUMO

Human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) and buprenorphine decrease HIV acquisition. Between November, 2016 and July, 2017, we surveyed persons (N = 200) at a drug detoxification center to assess their interest in PrEP and in buprenorphine, and to examine factors associated with such interests. Over the previous 6 months, 58% (117/200) injected drugs, 87% (173/200) used opioids, 50% (85/171) had condomless sex. Only 22% (26/117) of persons who injected drugs were aware of PrEP, yet 74% (86/116) and 72% (84/116) were interested in oral or injectable PrEP, respectively. Thirty-eight percent (47/125) of persons not receiving buprenorphine or methadone expressed interest in buprenorphine. After multivariable adjustment, Latinx ethnicity was associated with interest in PrEP (aOR 3.80; 95% CI 1.37-10.53), while male gender (aOR 2.76; 95% CI 1.21-6.34) was associated with interest in buprenorphine. Opportunities exist to implement PrEP and buprenorphine within drug detoxification centers.Clinical trial registration NCT02869776. Clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT02869776?term=Sabrina+Assoumou&cond=HIV+HCV&rank=1 .

9.
PLoS One ; 16(3): e0247806, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33770091

RESUMO

Upon discovery of the first archaeal species in the 1970s, life has been subdivided into three domains: Eukarya, Archaea, and Bacteria. However, the organization of the three-domain tree of life has been challenged following the discovery of archaeal lineages such as the TACK and Asgard superphyla. The Asgard Superphylum has emerged as the closest archaeal ancestor to eukaryotes, potentially improving our understanding of the evolution of life forms. We characterized the transportomes and their substrates within four metagenome-assembled genomes (MAGs), that is, Odin-, Thor-, Heimdall- and Loki-archaeota as well as the fully sequenced genome of Candidatus Prometheoarchaeum syntrophicum strain MK-D1 that belongs to the Loki phylum. Using the Transporter Classification Database (TCDB) as reference, candidate transporters encoded within the proteomes were identified based on sequence similarity, alignment coverage, compatibility of hydropathy profiles, TMS topologies and shared domains. Identified transport systems were compared within the Asgard superphylum as well as within dissimilar eukaryotic, archaeal and bacterial organisms. From these analyses, we infer that Asgard organisms rely mostly on the transport of substrates driven by the proton motive force (pmf), the proton electrochemical gradient which then can be used for ATP production and to drive the activities of secondary carriers. The results indicate that Asgard archaea depend heavily on the uptake of organic molecules such as lipid precursors, amino acids and their derivatives, and sugars and their derivatives. Overall, the majority of the transporters identified are more similar to prokaryotic transporters than eukaryotic systems although several instances of the reverse were documented. Taken together, the results support the previous suggestions that the Asgard superphylum includes organisms that are largely mixotrophic and anaerobic but more clearly define their metabolic potential while providing evidence regarding their relatedness to eukaryotes.

10.
Environ Microbiol ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33754415

RESUMO

Estuaries connect rivers with the ocean and are considered transition regions due to the continuous inputs from rivers. Microbiota from different sources converge and undergo succession in these transition regions, but their assembly mechanisms along environmental gradients remain unclear. Here, we found that salinity had a stronger effect on planktonic than on benthic microbial communities, and the dominant planktonic bacteria changed more distinctly than the dominant benthic bacteria with changes in salinity. The planktonic bacteria in the brackish water came mainly from seawater, which was confirmed in the laboratory, whereas the benthic bacteria were weakly affected by salinity, which appeared to be a mixture of the bacteria from riverine and oceanic sediments. Benthic bacterial community assembly in the sediments was mainly controlled by homogeneous selection and almost unaffected by changes in salinity, the dominant assemblage processes for planktonic bacteria changed dramatically along the salinity gradient, from homogeneous selection in freshwater to drift in seawater. Our results highlight that salinity is the key driver of estuarine microbial succession and that salinity is more important in shaping planktonic than benthic bacterial communities in the Yellow River estuary.

11.
J Obstet Gynaecol Res ; 47(5): 1711-1718, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33749101

RESUMO

AIM: To compare the effect of pituitrin local injection (PIT) and uterine artery embolization (UAE) as pretreatment before surgery during the management of cesarean scar pregnancy (CSP). METHODS: Forty-nine CSP patients diagnosed in our department of Suzhou Ninth People's Hospital from October 2017 to October 2019. All patients underwent hysteroscopy and negative pressure aspiration (for type I CSP) or laparoscopic wedge-resection (for type II and III CSP) following one of the preoperative treatments: PIT group (n = 26) and UAE group (n = 23). The baseline clinical data, intraoperative blood loss, blood transfusion rate, postoperative hospital stay, hospitalization expenses, postoperative pain, postoperative fever, postoperative serum ß-human chorionic gonadotropin (ß-hCG) level, and pregnancy outcome were reviewed and analyzed. RESULTS: There was no significant difference (p ≥ 0.05) between two groups in baseline characteristics including age, gravidity, previous cesarean section times, interval since last cesarean delivery, menolipsis time, maximum diameter of gestational sac or mass under ultrasound, fetal cardiac activity and preoperative ß-hCG level. There was no significant difference in blood loss, transfusion rate, and postoperative ß-hCG reduction percentage (p ≥ 0.05) either. The postoperative hospital stay, hospitalization expenses, postoperative pain, and postoperative fever rate in PIT group were significantly lower than those in UAE group (p < 0.05). Moreover, ß-hCG level of all patients turned negative 1 month after surgery successfully. CONCLUSIONS: PIT pretreatment seems to be a same effective, more economical, and with fewer side effects pretreatment method compared to traditional UAE pretreatment in the management of CSP.

12.
Biomed Res Int ; 2021: 6635594, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628798

RESUMO

Objective: Assessing excess adrenal hormones is important in patients with adrenal mass. Current screening tests for excess cortisol hormones are complex, so it cannot be done sometimes due to the limited medical resources. The aim of the study was to evaluate whether the neutrophil-lymphocyte ratio (NLR) can be used as an initial screening biomarker for Cushing's syndrome (CS) in patients with an adrenal mass. Methods: This retrospective study included a total of 185 patients with CS and 185 patients with nonfunctional adrenal adenoma (matched 1 : 1 by sex, body mass index, and discharge date). The NLR was compared between the two groups. The association between NLR and serum and urinary cortisol concentrations was analyzed, and an NLR cut-off value for CS screening was calculated. Results: NLR (3.38 (2.33, 5.45) vs. 2.13 (1.74, 3.00), P < 0.001) was significantly higher in the CS group than in the nonfunctional adenoma group. In CS patients, the NLR was positively associated with serum cortisol concentrations at 8 am, with 24-hour urine free cortisol and with serum cortisol after a 1 mg dexamethasone suppression test (P < 0.001 each). An NLR cut-off of 2.2 had a sensitivity of 80.0% and a specificity of 54.05%. The weighted Youden index for the NLR was similar to that of the 24-hour urine free cortisol and late-night serum cortisol tests, which are recommended initial tests for CS diagnosis. Conclusion: The NLR may be useful for initial screening for CS among patients with an adrenal mass as an easy and convenient marker.

13.
J Int Med Res ; 49(2): 300060521990127, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33535842

RESUMO

OBJECTIVE: We aimed to clarify the cognitive function of patients with chronic obstructive pulmonary disease (COPD) and different nutritional status. METHODS: Among 95 patients with COPD in this retrospective study, we administered the Nutritional Risk Screening 2002 (NRS 2002) and Mini-Mental State Examination (MMSE). We recorded patients' clinical characteristics, comorbidities, and laboratory measurements. According to NRS 2002 scores, patients were divided into two groups: no nutritional risk with NRS 2002 < 3 (n = 54) and nutritional risk, with NRS 2002 ≥ 3 (n = 41). RESULTS: We found a negative correlation between NRS 2002 and MMSE scores in participants with COPD (r = -0.313). Patients with nutritional risk were more likely to be cognitively impaired than those with no nutritional risk. Multivariate logistic regression analysis indicated that malnutrition was an independent risk factor for cognitive impairment, after adjusting for confounders (odds ratio [OR] = 4.120, 95% confidence interval [CI]: 1.072-15.837). We found a similar association between NRS 2002 and MMSE scores at 90-day follow-up using a Pearson's correlation test (r = -0.493) and logistic regression analysis (OR = 7.333, 95% CI: 1.114-48.264). CONCLUSIONS: Patients with COPD at nutritional risk are more likely to have cognitive impairment.

14.
Ecotoxicol Environ Saf ; 212: 112016, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33550079

RESUMO

The effects of Bacillus subtilis inoculation on the growth and Cd uptake of alfalfa were evaluated in this research using pot experiments, and the relevant biochemical mechanisms were first investigated by combined microbial diversity and nontarget metabolomics analyses. The results indicated that inoculation with alfalfa significantly decreased the amount of plant malondialdehyde (MDA) and improved the activities of plant antioxidant enzymes and soil nutrient cycling-involved enzymes, thereby promoting biomass by 29.4%. Inoculation also increased Cd bioavailability in rhizosphere soil by 12.0% and Cd removal efficiency by 139.3%. The biochemical mechanisms included enhanced bacterial diversity, transformed microbial community composition, regulated amounts of amino acids, fatty acids, carbohydrates, flavonoids and phenols in rhizosphere soil metabolites, and modulations of the corresponding Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These responses were beneficial to microbial activity, nutrient cycling, and Cd mobilization, detoxification, and decontamination by alfalfa in soil. This study, especially the newly identified differential metabolites and metabolic pathways, provides new insights into mechanism revelation and strategy development in microbe-assisted phytomanagement of heavy metal-contaminated soils.


Assuntos
Bacillus subtilis/metabolismo , Cádmio/metabolismo , Medicago sativa/metabolismo , Rizosfera , Poluentes do Solo/metabolismo , Bacillus subtilis/crescimento & desenvolvimento , Biodegradação Ambiental , Biodiversidade , Biomassa , Cádmio/análise , Medicago sativa/microbiologia , Metabolômica , Solo/química , Microbiologia do Solo , Poluentes do Solo/análise
15.
EMBO Rep ; 22(3): e50629, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33554448

RESUMO

Mitophagy is an essential cellular autophagic process that selectively removes superfluous and damaged mitochondria, and it is coordinated with mitochondrial biogenesis to fine tune the quantity and quality of mitochondria. Coordination between these two opposing processes to maintain the functional mitochondrial network is of paramount importance for normal cellular and organismal metabolism. However, the underlying mechanism is not completely understood. Here we report that PGC-1α and nuclear respiratory factor 1 (NRF1), master regulators of mitochondrial biogenesis and metabolic adaptation, also transcriptionally upregulate the gene encoding FUNDC1, a previously characterized mitophagy receptor, in response to cold stress in brown fat tissue. NRF1 binds to the classic consensus site in the promoter of Fundc1 to upregulate its expression and to enhance mitophagy through its interaction with LC3. Specific knockout of Fundc1 in BAT results in reduced mitochondrial turnover and accumulation of functionally compromised mitochondria, leading to impaired adaptive thermogenesis. Our results demonstrate that FUNDC1-dependent mitophagy is directly coupled with mitochondrial biogenesis through the PGC-1α/NRF1 pathway, which dictates mitochondrial quantity, quality, and turnover and contributes to adaptive thermogenesis.

16.
JAMA Netw Open ; 4(2): e2037259, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33587136

RESUMO

Importance: The United States is experiencing a crisis of opioid overdose. In response, the US Department of Health and Human Services has defined a goal to reduce overdose mortality by 40% by 2022. Objective: To identify specific combinations of 3 interventions (initiating more people to medications for opioid use disorder [MOUD], increasing 6-month retention with MOUD, and increasing naloxone distribution) associated with at least a 40% reduction in opioid overdose in simulated populations. Design, Setting, and Participants: This decision analytical model used a dynamic population-level state-transition model to project outcomes over a 2-year horizon. Each intervention scenario was compared with the counterfactual of no intervention in simulated urban and rural communities in Massachusetts. Simulation modeling was used to determine the associations of community-level interventions with opioid overdose rates. The 3 examined interventions were initiation of more people to MOUD, increasing individuals' retention with MOUD, and increasing distribution of naloxone. Data were analyzed from July to November 2020. Main Outcomes and Measures: Reduction in overdose mortality, medication treatment capacity needs, and naloxone needs. Results: No single intervention was associated with a 40% reduction in overdose mortality in the simulated communities. Reaching this goal required use of MOUD and naloxone. Achieving a 40% reduction required that 10% to 15% of the estimated OUD population not already receiving MOUD initiate MOUD every month, with 45% to 60%% retention for at least 6 months, and increased naloxone distribution. In all feasible settings and scenarios, attaining a 40% reduction in overdose mortality required that in every month, at least 10% of the population with OUD who were not currently receiving treatment initiate an MOUD. Conclusions and Relevance: In this modeling study, only communities with increased capacity for treating with MOUD and increased MOUD retention experienced a 40% decrease in overdose mortality. These findings could provide a framework for developing community-level interventions to reduce opioid overdose death.


Assuntos
Técnicas de Apoio para a Decisão , Naloxona/provisão & distribução , Antagonistas de Entorpecentes/provisão & distribução , Tratamento de Substituição de Opiáceos/estatística & dados numéricos , Retenção nos Cuidados/estatística & dados numéricos , Simulação por Computador , Humanos , Massachusetts , População Rural , População Urbana
17.
Appl Environ Microbiol ; 87(9)2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33608292

RESUMO

Bacterial proline-alanine-alanine-arginine (PAAR) proteins are located at the top of the type VI secretion system (T6SS) nanomachine and carry and deliver effectors into neighboring cells. Many PAAR proteins are fused with a variable C-terminal extended domain (CTD). Here, we report that two paar-ctd genes (MXAN_RS08765 and MXAN_RS36995) located in two homologous operons are involved in different ecological functions of Myxococcus xanthus MXAN_RS08765 inhibited the growth of plant-pathogenic fungi, while MXAN_RS36995 was associated with the colony-merger incompatibility of M. xanthus cells. These two PAAR-CTD proteins were both toxic to Escherichia coli cells, while MXAN_RS08765, but not MXAN_RS36995, was also toxic to Saccharomyces cerevisiae cells. Their downstream adjacent genes, i.e., MXAN_RS08760 and MXAN_RS24590, protected against the toxicities. The MXAN_RS36995 protein was demonstrated to have nuclease activity, and the activity was inhibited by the presence of MXAN_RS24590. Our results highlight that the PAAR proteins diversify the CTDs to play divergent roles in M. xanthus IMPORTANCE The type VI secretion system (T6SS) is a bacterial cell contact-dependent weapon capable of delivering protein effectors into neighboring cells. The PAAR protein is located at the top of the nanomachine and carries an effector for delivery. Many PAAR proteins are extended with a diverse C-terminal sequence with an unknown structure and function. Here, we report two paar-ctd genes located in two homologous operons involved in different ecological functions of Myxococcus xanthus; one has antifungal activity, and the other is associated with the kin discrimination phenotype. The PAAR-CTD proteins and the proteins encoded by their downstream genes form two toxin-immunity protein pairs. We demonstrated that the C-terminal diversification of the PAAR-CTD proteins enriches the ecological functions of bacterial cells.


Assuntos
Proteínas de Bactérias/genética , Myxococcus xanthus/genética , Proteínas de Bactérias/fisiologia , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Fungos/crescimento & desenvolvimento , Loci Gênicos , Óperon , Fenótipo , Domínios Proteicos , Sistemas de Secreção Tipo VI
18.
J Chem Theory Comput ; 17(3): 1318-1325, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33593057

RESUMO

Although quantum mechanical/molecular mechanics (QM/MM) methods are now routinely applied to the studies of chemical reactions in condensed phases and enzymatic reactions, they may experience technical difficulties when the reactive region is varying over time. For instance, when the solvent molecules are directly participating in the reaction, the exchange of water molecules between the QM and MM regions may occur on a time scale comparable to the reaction time. To cope with this situation, several adaptive QM/MM schemes have been proposed. However, these methods either add significantly to the computational cost or introduce artificial restraints to the system. In this work, we developed a novel adaptive QM/MM scheme and applied it to the study of a nucleophilic addition reaction. In this scheme, the configuration sampling was performed with a small QM region (without solvent molecules), and the thermodynamic properties under another potential energy function with a larger QM region (with a certain number of solvent molecules and/or different levels of QM theory) are computed via extrapolation using the reference-potential method. Our simulation results show that this adaptive QM/MM scheme is numerically stable, at least for the case studied in this work. Furthermore, this method also offers an inexpensive way to examine the convergence of the QM/MM calculation with respect to the size of the QM region.

19.
Mitochondrion ; 57: 222-229, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33401012

RESUMO

Childhood-onset dystonia with optic atrophy and basal ganglia abnormalities is an extremely rare autosomal recessive mitochondrial disease caused by biallelic mutations in MECR. Using whole-exome sequencing, we identified a novel homozygous MECR mutation (c.910G > T, p.Asp304Tyr) in a Chinese patient with childhood-onset dystonia and basal ganglia abnormalities, without optic atrophy. With lipoic acid treatment, the disease progression was under control, and neither visual impairment nor optic atrophy was observed. To our knowledge, this is the first study about MECR-related mitochondrial disease in a Chinese patient and the first to report that supplementation with lipoic acid is a possible effective therapeutic strategy for this disease.

20.
Chemosphere ; 271: 129566, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33460896

RESUMO

Nitrogen amendment is known to effectively enhance the bioremediation of hydrocarbon-contaminated soil, but the nitrogen metabolism in this process is not well understood. To unravel the nitrogen metabolic pathway(s) of diesel contaminated soil, six types of nitrogen sources were added to the diesel contaminated soil. Changes in microbial community and soil enzyme genes were investigated by metagenomics analysis and chemical analysis through a 30-day incubation study. The results showed that ammonium based nitrogen sources significantly accelerated the degradation of total petroleum hydrocarbon (TPH) (79-81%) compared to the control treatment (38%) and other non-ammonium based nitrogen amendments (43-57%). Different types of nitrogen sources could dramatically change the microbial community structure and soil enzyme gene abundance. Proteobacteria and Actinobacteria were identified as the two dominant phyla in the remediation of diesel contaminated soil. Metagenomics analysis revealed that the preferred metabolic pathway of nitrogen was from ammonium to glutamate via glutamine, and the enzymes governing this transformation were glutamine synthetase and glutamate synthetase; while in nitrate based amendment, the conversion from nitrite to ammonium was restrained by the low abundance of nitrite reductase enzyme and therefore retarded the TPH degradation rate. It is concluded that during the process of nitrogen enhanced bioremediation, the most efficient nitrogen cycling direction was from ammonium to glutamine, then to glutamate, and finally joined with carbon metabolism after transforming to 2-oxoglutarate.


Assuntos
Petróleo , Poluentes do Solo , Biodegradação Ambiental , Hidrocarbonetos , Redes e Vias Metabólicas/genética , Metagenômica , Nitrogênio/análise , Solo , Microbiologia do Solo , Poluentes do Solo/análise
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