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2.
Biochem Pharmacol ; 171: 113710, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31726046

RESUMO

Enteric viruses that inhabit the intestine have profound effects on innate and adaptive immunity of the gut and thus distant organs. Acute pancreatitis (AP) is a common abdominal inflammatory disease, in which gut bacteria play an indispensable part, particularly in the severe form with local and systemic complications. So far, little is known about the role of enteric viruses in the pathophysiology of AP. In this study, we evaluated the effect of enteric virus depletion by oral anti-viral cocktail (AVC) on caerulein (Cae)-hyperstimulation induced experimental AP and underlying mechanisms. We found that AVC treatment alleviated experimental AP, accompanied by suppressed innate immune cell infiltration and TLR9 expression and signaling in pancreas and intestine. Furthermore, AVC administration reduced AP-induced interleukin-6 (IL-6) production, IL-6-activated signal transducers and activators of transcription 3 (STAT3) signaling. Concordantly, expression of AP-induced STAT3-responsive chemokines, especially monocyte chemotactic protein-1 (MCP-1) and chemokine (C-X-C motif) ligand 1 (CXCL1) was reduced, thereby contributing to modulated pancreatic immune milieu. Treatment of mice with a toll-like receptor 9 (TLR9) agonist abolished the protective effect of AVC by activation of IL6/STAT3 signaling and downstream chemokine production. Conversely, treatment of mice with TLR9 antagonists, mimicking AVC, exerted protective effects against AP. Collectively, these results suggest that depletion of enteric viruses protects mice from experimental AP through inhibiting TLR9 signaling. Our study therefore implies a previously unrecognized role of enteric viruses in AP.

3.
Pharmacol Res ; 152: 104592, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31830521

RESUMO

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease with mysterious pathogenesis and limited effective therapies. The aberrantly activated lung myofibroblasts with resultant excessive accumulation of extracellular matrix is a central event in the progression of pulmonary fibrosis. Lysine-specific demethylase 1 (LSD1) has been suggested to epigenetically regulate cell differentiation, migration and invasion in tumor microenvironment. However, its function in pulmonary fibrosis remains unclear. The present study aimed to investigate the potential effect and underlying mechanisms of LSD1 in pulmonary fibrosis. Here, we found that LSD1 expression was elevated in lung tissues of mice with bleomycin-induced pulmonary fibrosis and lung fibroblasts treated with transforming growth factor-ß1 (TGF-ß1). In vivo knockdown of LSD1 by lentiviral shRNA transfection attenuated pulmonary fibrosis in mice, as evidenced by improved lung morphology, decreased lung coefficient and collagen secretion, and down-regulated α-SMA, collagen type I alpha and fibronectin expression in lungs. Additionally, in vitro knockdown of LSD1 inhibited the differentiation of fibroblasts to myofibroblasts, and decreased myofibroblast migration. By further mechanistic analysis, we demonstrated that knockdown of LSD1 prevented fibroblast--to-myofibroblast differentiation and subsequent pulmonary fibrosis by suppressing TGF-ß1/Smad3 signaling pathway through modulation of a balance between histone H3 lysine 9 methylation and histone H3 lysine 4 methylation. Together, our data indicate that LSD1 activation contributes to pulmonary myofibroblast differentiation and fibrosis by targeting TGF-ß1/Smad3 signaling, and suggest LSD1 as a therapeutic target for the treatment of pulmonary fibrosis.

4.
Clin Infect Dis ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31734699

RESUMO

BACKGROUND: Evaluation of a licensed inactivated EV71 vaccine is needed in a phase IV study with a large population to identify its effectiveness and safety for further application. METHODS: An open-label and controlled trial involving a large population of 155,995 children aged 6-71 months is performed; 40,724 were enrolled in the vaccine group and received 2 doses of inactivated EV71 vaccine at an interval of 1 month, and the remaining children were used as the control group. The EV71-infected hand, foot and mouth disease (HFMD) cases were monitored in the vaccine and control groups during a follow-up period of 14 months since the 28th days post inoculation through the local database of Notifiable Infectious Diseases Network. The effectiveness of the vaccine was estimated by comparing the incidence density in the vaccine group versus that in the control group based upon EV71 infected patients identified via laboratory testing. In parallel, the active and passive surveillance for safety of the vaccine was conducted by home or telephone visits and by using the Adverse Event Following Immunization (AEFI) system, respectively. RESULTS: An overall level of 89.7% (95% confidence interval [CI], 24.0 to 98.6) vaccine effectiveness (VE) against EV71 infection and a 4.58% rate of reported AEs were observed. Passive surveillance demonstrated a 0.31% rate of reported common minor reactions. CONCLUSIONS: The clinical protection and safety of the EV71 vaccine were demonstrated in the immunization of a large population. CLINICAL TRIALS REGISTRATION: NCT03001986.

5.
Adv Mater ; 31(48): e1905405, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31595583

RESUMO

Most natural materials expand uniformly in all directions upon heating. Artificial, engineered systems offer opportunities to tune thermal expansion properties in interesting ways. Previous reports exploit diverse design principles and fabrication techniques to achieve a negative or ultralow coefficient of thermal expansion, but very few demonstrate tunability over different behaviors. This work presents a collection of 2D material structures that exploit bimaterial serpentine lattices with micrometer feature sizes as the basis of a mechanical metamaterials system capable of supporting positive/negative, isotropic/anisotropic, and homogeneous/heterogeneous thermal expansion properties, with additional features in unusual shearing, bending, and gradient modes of thermal expansion. Control over the thermal expansion tensor achieved in this way provides a continuum-mechanics platform for advanced strain-field engineering, including examples of 2D metamaterials that transform into 3D surfaces upon heating. Integrated electrical and optical sources of thermal actuation provide capabilities for reversible shape reconfiguration with response times of less than 1 s, as the basis of dynamically responsive metamaterials.

6.
Front Neurosci ; 13: 851, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474821

RESUMO

This study aimed to identify the mechanism behind idiopathic sudden sensorineural hearing loss (ISSNHL) in patients with tinnitus by investigating aberrant activity in areas of the brain and functional connectivity. High-density electroencephalography (EEG) was used to investigate central nervous changes in 25 ISSNHL subjects and 27 healthy controls. ISSNHL subjects had significantly reduced activity in the left frontal lobe at the alpha 2 frequency band compared with controls. Linear lagged connectivity and lagged coherence analysis showed significantly reduced functional connectivity between the temporal gyrus and supramarginal gyrus at the gamma 2 frequency band in the ISSNHL group. Additionally, a significantly reduced functional connectivity was found between the central cingulate gyrus and frontal lobe under lagged phase synchronization analysis. These results strongly indicate inhibition of brain area activity and change in functional connectivity in ISSNHL with tinnitus patients.

7.
Front Immunol ; 10: 1733, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417546

RESUMO

Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25+Foxp3+CD4+ regulatory T cell (Foxp3+ Treg) in the pancreas, pancreatic and mesenteric lymph nodes was analyzed by flow cytometry. We found that LMP supplementation ameliorated T1D development in non-obese diabetic (NOD) mice, as evidenced by decreasing diabetes incidence and fasting glucose levels in LMP fed NOD mice. Further microbiota analysis revealed that LMP supplementation prevented T1D-associated caecal dysbiosis and selectively enriched caecal bacterial species to produce more SCFAs. The LMP-mediated microbial balance further enhanced caecal barrier function and shaped gut-pancreatic immune environment, as characterized by higher expression of tight junction proteins claudin-1, ZO-2 in caecum, increased Foxp3+ Treg population and decreased NLRP3 inflammasome activation in both caecum and pancreas. The microbiota-dependent beneficial effect of LMP on T1D was further proven by the fact that aberration of caecal microbiota by ABX treatment worsened T1D autoimmunity and could be restored with transfer of feces of LMP-fed NOD mice. These data demonstrate that this novel LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment. This finding opens a realistic option for gut microbiota manipulation and prevention of T1D in humans.

8.
Mol Nutr Food Res ; 63(21): e1900307, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31423661

RESUMO

SCOPE: This study aims to examine the protective effects of specific low-methoxyl pectin (LMP) on the development of type 1 diabetes (T1D). METHODS AND RESULTS: Female non-obese diabetic (NOD) mice are weaned onto either control or 5% LMP supplemented diets for up to 22 weeks of age. T1D incidence, gut barrier function, and pancreatic-gut immune responses are analyzed. LMP supplementation significantly dampened the onset of T1D in NOD mice. LMP supplementation induces caecal homeostasis, as indicated by the increasing SCFAs production, higher expression of tight junction proteins claudin 1, zonula occludens-2 in caecum. Furthermore, LMP-mediated caecal homeostasis impacts gut-pancreatic immunity, as evidenced by increased regulatory T cell population, modulated inflammatory cytokine expression, and suppressed NOD like receptor protein 3 (NLRP3) inflammasome activation in both caecum and pancreas. CONCLUSION: The data demonstrate that LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment, providing a scientific basis for using LMP as a novel functional supplementation to intervene T1D.

9.
Br J Pharmacol ; 176(23): 4446-4461, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31347703

RESUMO

BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a common acute abdominal condition, frequently associated with intestinal barrier dysfunction, which aggravates AP retroactively. Butyrate exhibits anti-inflammatory effects in a variety of inflammatory diseases. However, its potential beneficial effect on AP and the underlying mechanisms have not been investigated. EXPERIMENTAL APPROACH: Experimental AP was induced by caerulein hyperstimulation in wild-type and GPR109A-/- mice. Sodium butyrate was administered intragastrically for 7 days prior to caerulein hyperstimulation. Anti-inflammatory mechanisms of butyrate were further investigated in peritoneal macrophages. KEY RESULTS: Butyrate prophylaxis attenuated AP as shown by reduced serum amylase and lipase levels, pancreatic oedema, myeloperoxidase activity, and improved pancreatic morphology. Amelioration of pancreatic damage by butyrate was associated with reduced levels of TNF-α, IL-6, and CCL2 and suppressed activation of the NLRP3 inflammasome in both pancreas and colon. Further, butyrate ameliorated pancreatic inflammation by suppressing interactions between histone deacetylase 1 (HDAC1) and AP1 and STAT1 with increased histone acetylation at H3K9, H3K14, H3K18, and H3K27 loci, resulting in suppression of NLRP3 inflammasome activation and modulation of immune cell infiltration in pancreas. Additionally, butyrate mediated STAT1/AP1-NLRP3 inflammasome suppression via HDAC1 inhibition was demonstrated in peritoneal macrophage. In colon, butyrate inhibited NLRP3 inflammasome activation via GPR109A. Accordingly, the modulatory effects of butyrate on AP, AP-associated gut dysfunction, and NLRP3 inflammasome activation were diminished in GPR109A-/- mice. CONCLUSION AND IMPLICATIONS: Our study dissected tissue-specific anti-inflammatory mechanisms of butyrate during AP, suggesting that increased colonic levels of butyrate may be a strategy to protect against AP.

10.
J Environ Manage ; 244: 189-198, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31125870

RESUMO

In this study, a new two-stage stochastic interval-parameter fuzzy programming strategy model is developed for regional economic-environment sustainability, considering the planning and management of water-resources and water-environment systems under uncertainty. The model is capable in addressing the complexity and uncertainties of the water system,which contains the concepts of economics and environment within an optimization framework. The objective of this research is to develop a participatory integrated assessment model, based on the water benefit and water environment security, with an application in the Sanjiang Plain area, China. The methodology intendeds to capture the complexity and scarcity of water management problems, incorporating the relevant sectors, as well as the different levels of water involved in water management decision. The model is applied through maximizing the benefits of water during livelihood, production and ecology. In addition, the model considers the constraints of water quantity and water quality. Then, a variety of decision results are calculated under different conditions of water shortage. The developed method is applied to plan resources management and develop regional environment sustainability. The generated results can assist the decision makers in not only making resources allocation strategies but also gaining insights into the benefit between economic and environment objective.


Assuntos
Modelos Teóricos , Água , China , Processos Estocásticos , Recursos Hídricos
11.
Front Neurosci ; 13: 443, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31133786

RESUMO

In order to clarify the central reorganization in acute period of hearing loss, this study explored the aberrant dynamics of electroencephalogram (EEG) microstates and the correlations with the features of idiopathic sudden sensorineural hearing loss (ISSNHL) and tinnitus. We used high-density EEG with 128 channels to investigate alterations in microstate parameters between 25 ISSNHL patients with tinnitus and 27 healthy subjects. This study also explored the associations between microstate characteristics and tinnitus features. Microstates were clustered into four categories. There was a reduced presence of microstate A in amplitude, coverage, lifespan, frequency and an increased presence of microstate B in frequency in ISSNHL patients with tinnitus. According to the syntax analysis, a reduced transition from microstate C to microstate A and an increased transition from microstate C to microstate B were found in ISSNHL subjects. In addition, the significant negative correlations were found between Tinnitus Handicap Inventory (THI) scores and frequency of microstate A as well as between THI scores and the probability of transition from microstate D to microstate A. While THI was positively correlated with the transition probability from microstate D to microstate B. To sum up, the significant differences in the characteristics of resting-state EEG microstates were found between ISSNHL subjects with tinnitus and healthy controls. This study suggests that the alterations of central neural networks occur in acute stage of hearing loss and tinnitus. And EEG microstate may be considered as a useful tool to study the whole brain network in ISSNHL patients.

12.
ChemMedChem ; 14(6): 645-662, 2019 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-30702807

RESUMO

Since the discovery of a flavin-dependent thymidylate synthase (ThyX or FDTS) that is absent in humans but crucial for DNA biosynthesis in a diverse group of pathogens, the enzyme has been pursued for the development of new antibacterial agents against Mycobacterium tuberculosis, the causative agent of the widespread infectious disease tuberculosis (TB). In response to a growing need for more effective anti-TB drugs, we have built upon our previous screening efforts and report herein an optimization campaign of a novel series of inhibitors with a unique inhibition profile. The inhibitors display competitive inhibition toward the methylene tetrahydrofolate cofactor of ThyX, enabling us to generate a model of the compounds bound to their target, thus offering insight into their structure-activity relationships.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Timidilato Sintase/antagonistas & inibidores , Mycobacterium tuberculosis/enzimologia , Relação Estrutura-Atividade
13.
Phlebology ; 34(1): 40-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29635965

RESUMO

OBJECTIVES: To report *The first two authors contributed equally to this work. our clinical experience on diagnostic criteria and endovascular management in patients with iliac venous compression syndrome. METHOD: Between July 2013 and May 2015, 85 consecutive patients with suspected iliac venous compression syndrome were evaluated by transfemoral venography and intravascular ultrasonography. Venographic evidence of iliac venous occlusion, stenosis, or pelvic collateral vessels, and the degree of stenosis as examined with intravascular ultrasonography were recorded. The endovascular procedure, complications, clinical outcome, and the Venous Clinical Severity Score were evaluated before and after the intervention. RESULTS: Of the 85 limbs, 66 cases of iliac venous compression syndrome were confirmed and 19 cases were excluded. In all of the 66 patients, we successfully performed endovascular intervention (22 balloon dilations, 44 balloon dilations + stenting). Two patients with stent implantation developed acute lower extremity deep vein thrombosis, resulted in successful lysis of the thrombus with catheter-directed thrombolysis. CONCLUSIONS: The presence of intraluminal spurs and pelvic collateral vessels represents not only pathological and anatomical changes by long-term mechanical compression, but also indicators of the severity of iliac venous compression syndrome. The degree of stenosis cannot accurately represent the severity and treatment of iliac venous compression syndrome, especially in the right iliac vein. Endovascular intervention is a safe and effective treatment that reduces lower extremity symptoms. Full and intentional dilation of the intraluminal spurs is an important technical aspect, which is often ignored.


Assuntos
Procedimentos Endovasculares , Veia Ilíaca , Síndrome de May-Thurner , Flebografia , Ultrassonografia de Intervenção , Adulto , Idoso , Feminino , Seguimentos , Humanos , Veia Ilíaca/diagnóstico por imagem , Veia Ilíaca/fisiopatologia , Veia Ilíaca/cirurgia , Masculino , Síndrome de May-Thurner/diagnóstico por imagem , Síndrome de May-Thurner/fisiopatologia , Síndrome de May-Thurner/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
IEEE Trans Cybern ; 49(7): 2431-2443, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29994295

RESUMO

For multisensor linear time-varying system with non-Gaussian measurement noise, how to design distributed robust estimator to increase the accuracy and robustness to outliers at a relatively low computation and communication cost is a fundamental task. This paper proposes a fast distributed variational Bayesian (VB) filtering algorithm to recursively estimate the state and noise distribution over three conventional sensor networks: 1) incremental-based; 2) diffusion-based; and 3) consensus-based. To be specific, the non-Gaussian measurement noise of each sensor is modeled as Student- t distribution, and the system state and the parameters of the distribution are estimated via VB approach in each iteration step. An interaction scheme is then added to obtain the global optimal parameter by fusing the local optimal parameters over incremental, diffusion, and consensus communication topology. An efficient sensor selection criterion under these topologies based on the Cramér-Rao lower bound is proposed to reduce the communication and computation burden. Compared with the existing centralized VB filtering algorithms, the proposed algorithm in this paper can extensively increase the robustness to node or link failure at a lower computation cost with acceptable estimation performance and communication load. The theoretic results and simulation results are given to show the efficiency of our proposed algorithm.

15.
Stand Genomic Sci ; 13: 29, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386456

RESUMO

Pseudaminobacter manganicus JH-7T (= KCTC 52258T = CCTCC AB 2016107T) is a Gram-staining-negative, aerobic and non-motile strain that was isolated from a manganese mine. The strain JH-7T shows multiple heavy metal resistance and can effectively remove Mn2+ and Cd2+. In addition, it is able to produce exopolysaccharides (EPS), which may contribute to metal remove/adsorption. Thus, strain JH-7T shows a great potential in bioremediation of heavy metal-contaminated environment. In this study, we report the draft genomic sequence of P. manganicus JH-7T and compare it to related genomes. Strain JH-7T has a 4,842,937 bp genome size with a G + C content of 61.2%, containing 4504 protein-coding genes and 71 RNA genes. A large number of putative genes associated with heavy metal resistance and EPS synthesis are found in the genome.

16.
Front Immunol ; 9: 751, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719535

RESUMO

Acute pancreatitis (AP) is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF)-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications.


Assuntos
Fatores Imunológicos/uso terapêutico , Lactose/uso terapêutico , Macrófagos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Pancreatite/tratamento farmacológico , Doença Aguda , Animais , Ceruletídeo , Citocinas/imunologia , Feminino , Fatores Imunológicos/farmacologia , Lactose/farmacologia , Macrófagos/imunologia , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/imunologia , Pancreatite/patologia , Fenótipo
17.
Front Immunol ; 9: 849, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29719542

RESUMO

[This corrects the article on p. 762 in vol. 8, PMID: 28713382.].

18.
Horm Behav ; 102: 129-138, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29778459

RESUMO

Bisphenol-A (BPA) is a well-known environmental endocrine disruptor. Developmental exposure to BPA affected a variety of behaviors in multiple model organisms. Our recent study found that exposure to BPA during adulthood aggravated anxiety- and depression-like states in male mice but not in females. In this study, 11-w-old gonadectomied (GDX) male mice daily received subcutaneous injections of testosterone propionate (TP, 0.5 mg/kg), TP and BPA (0.04, 0.4, or 4 mg/kg), or vehicle for 45 days. BPA (0.4 or 4 mg/kg) did not affect the elevated plus maze task of GDX mice but shortened the time on open arms and decreased the frequency of head dips of sham and TP-GDX mice. In forced swim task, BPA prolonged the total time of immobility of both sham and TP-GDX mice but not GDX mice. In addition, BPA reduced the levels of T in the serum and the brain of sham and TP-GDX mice. Western blot analysis further showed that BPA reduced the levels of androgen receptor (AR) and GABA(A)α2 receptor of the hippocampus and the amygdala in sham and inhibited the rescue of TP in these proteins levels of GDX mice. Meanwhile, BPA decreased the level of phospho-ERK1/2 in these two brain regions of sham and TP-GDX mice. These results suggest that long-term exposure to BPA inhibited TP-improved anxiety- and depression-like behaviors in GDX male mice. The down-regulated levels of GABA(A)α2 receptor and AR and an inhibited activity of ERK1/2 pathway in the hippocampus and the amygdala may be involved in these process.


Assuntos
Ansiedade/prevenção & controle , Compostos Benzidrílicos/farmacologia , Depressão/prevenção & controle , Disruptores Endócrinos/farmacologia , Fenóis/farmacologia , Testosterona/farmacologia , Animais , Ansiedade/induzido quimicamente , Comportamento Animal/efeitos dos fármacos , Depressão/induzido quimicamente , Antagonismo de Drogas , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Orquiectomia , Testosterona/sangue
19.
Nat Commun ; 9(1): 1383, 2018 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-29643375

RESUMO

Understanding the mechanisms that promote cooperative behaviors of bacteria in their hosts is of great significance to clinical therapies. Environmental stress is generally believed to increase competition and reduce cooperation in bacteria. Here, we show that bacterial cooperation can in fact be maintained because of environmental stress. We show that Pseudomonas aeruginosa regulates the secretion of iron-scavenging siderophores in the presence of different environmental stresses, reserving this public good for private use in protection against reactive oxygen species when under stress. We term this strategy "conditional privatization". Using a combination of experimental evolution and theoretical modeling, we demonstrate that in the presence of environmental stress the conditional privatization strategy is resistant to invasion by non-producing cheaters. These findings show how the regulation of public goods secretion under stress affects the evolutionary stability of cooperation in a pathogenic population, which may assist in the rational development of novel therapies.


Assuntos
Antibiose/fisiologia , Ferro/metabolismo , Oligopeptídeos/biossíntese , Pseudomonas aeruginosa/fisiologia , Sideróforos/biossíntese , Simbiose/fisiologia , Antibacterianos/farmacologia , Antibiose/efeitos dos fármacos , Antibiose/efeitos da radiação , Evolução Biológica , Contagem de Colônia Microbiana , Fluoresceínas/química , Corantes Fluorescentes/química , Oligopeptídeos/metabolismo , Fótons/efeitos adversos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Sideróforos/metabolismo , Estresse Fisiológico , Simbiose/efeitos dos fármacos , Simbiose/efeitos da radiação , Tobramicina/farmacologia
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