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1.
Theranostics ; 9(24): 7403-7416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695776

RESUMO

Bone marrow mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been widely used for treating myocardial infarction (MI). However, low retention and short-lived therapeutic effects are still significant challenges. This study aimed to determine whether incorporation of MSC-derived sEVs in alginate hydrogel increases their retention in the heart thereby improving therapeutic effects. Methods: The optimal sodium alginate hydrogel incorporating sEVs system was determined by its release ability of sEVs and rheology of hydrogel. Ex vivo fluorescence imaging was utilized to evaluate the retention of sEVs in the heart. Immunoregulation and effects of sEVs on angiogenesis were analyzed by immunofluorescence staining. Echocardiography and Masson's trichrome staining were used to estimate cardiac function and infarct size. Results: The delivery of sEVs incorporated in alginate hydrogel (sEVs-Gel) enhanced their retention in the heart. Compared with sEVs only treatment (sEVs), sEVs-Gel treatment significantly decreased cardiac cell apoptosis and promoted the polarization of macrophages at day 3 after MI. sEVs-Gel treatment also increased scar thickness and angiogenesis at four weeks post-infarction. Measurement of cardiac function and infarct size were significantly better in the sEVs-Gel group than in the group treated with sEVs only. Conclusion: Delivery of sEVs incorporated in alginate hydrogel provides a novel approach of cell-free therapy and optimizes the therapeutic effect of sEVs for MI.

2.
BMC Cancer ; 19(1): 1001, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31653236

RESUMO

BACKGROUND: The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM. METHODS: Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis. RESULTS: The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6-3.2%) and 1.8% (95% CI: 1.2-2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11-40 years old, plateaued for patients aged 41-90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75-0.84; p < .001) and a favourable prognosis for respiratory system cancers (pooled HR = 0.81; 95% CI: 0.71-0.92; p < .001). However, no significant associations existed for other cancers. Male non-sex-specific cancer patients and those with male-leaning genetic variations or hormonal status have a greater likelihood of developing BM than female patients. CONCLUSIONS: Female sex was associated with fewer BM in various non-sex-specific cancers, and the effect was constant with changes in age. Female sex showed a protective effect exclusively on the prognosis of respiratory system cancers.

3.
Chem Commun (Camb) ; 55(87): 13096-13099, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31612162

RESUMO

A fluorescence "turn-on" method for digestion-free analysis of 4-thiouridine (s4U) in nucleic acids was developed in this work based on the oxidative amination of s4U by fluoresceinamine (FAM-NH2) and periodate (IO4-). It was 125-fold more sensitive for s4U detection than the traditional UV330 absorption method, and showed excellent selectivity to s4U over 2-thiouridine (s2U) analogues and biological thiols.

4.
Bioinspir Biomim ; 14(6): 066015, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557748

RESUMO

Carpenter ants possess the characteristics of division of labor, communication between individuals, cooperation, and the ability to solve problems. Inspired by the carpenter ant, we designed electromagnetically controlled ant millirobots that can move, clamp, and work cooperatively. The robot can receive power wirelessly to actuate its ionic polymer-metal composite gripper. Further, two robots can be controlled to manipulate small components individually or cooperatively. Dual-robot manipulation is found to take 76.7% of the time required for single-robot manipulation. The results show that complicated manipulation can be performed by robots that are multifunctional and flexible by utilizing electromagnetic actuation, intelligent materials, and wireless power transmission.

5.
Cornea ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31517721

RESUMO

PURPOSE: Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis. METHODS: We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs. RESULTS: Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin. CONCLUSIONS: This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.

6.
Mater Sci Eng C Mater Biol Appl ; 105: 110036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546358

RESUMO

Rapid vascularization and long-term antibacterial property are desirable characteristics of the next-generation implants in orbital reconstruction. In this study, the new diopside-based orbital implants were developed by direct ink writing of diopside (CaMgSi2O6; DIO) and low-melt bioactive glass (BG)-assisted sintering approaches. The mechanical tests showed that the addition 5% or 10% BG could readily enhance the compressive strength of the DIO porous bioceramics after sintering at 1150 °C. The Tris buffer immersion test in vitro indicated that the porous bioceramics exhibited appreciable mechanical stability and very limited mass loss (<3.5%) after 8 weeks. The DIO/10BG porous bioceramic sintered at 1150 °C or 1250 °C could promote appreciable angiogenesis response at the early stage (2-6 weeks) of implantation in the rabbit panniculus carnosus muscle models in vivo. It is interesting that the steam autoclaved bioceramics exhibited outstanding contact-active inhibition against Staphylococcus aureus and Pseudomonas aeruginosa, but as-sintered bioceramics showed no antibacterial effect. It is reasonable to consider that our strategy paves the way toward a simple and effective approach to fabricate the multifunctional tailormade implants for orbital implantation, thus accelerating the clinical translation of biomaterials research.

7.
Chemosphere ; 237: 124490, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31394451

RESUMO

The occurrence of fungi in water supply systems causes many environmental problems (e.g., odor, taste, turbidity, formation of mycotoxins); it has been an area of increasing concern in recent years. Ultraviolet irradiation can inactivate fungi efficiently. However, its reactivation poses further challenges in water purification. The reactivation characteristics of waterborne fungi under different environmental conditions have rarely been reported. In this study, the effects of temperatures and dark delay on the reactivation of three genera of fungal spores (Trichoderma harzianum, Aspergillus niger, Penicillium polonicum) were evaluated. The reactivation levels among these fungal spores were compared in phosphate buffer solution (PBS) and in real groundwater. It was found that lower temperature can inhibit the photoreactivation of fungi, whereas higher temperatures would promote the process. A long-term dark delay can inhibit the photoreactivation of fungi effectively. The dark repair of fungal spores almost do not occur neither in PBS nor in real groundwater. Finally, the photoreactivation percentage in real groundwater was higher than that in PBS. This study will provide a basis for controlling the reactivation of fungi in water.

8.
Int J Cardiol ; 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400886

RESUMO

BACKGROUND: The role of family history in determining excess risk of coronary heart disease (CHD) in South Asians compared with Europeans is unclear. We hypothesized that family history would be more strongly associated with CHD in South Asians. METHODS: We performed cross-sectional analyses of 20-year follow-up data from SABRE (Southall And Brent Revisited) population-based study. Initial recruitment (1988-1991) was by random selection from general practitioners' lists in north-west London. 974 Europeans and 734 South Asians completed follow-up questionnaire (2008-2011) and had complete CHD and family history data. 831 participants without cardiovascular disease had complete coronary artery calcium (CAC) data. RESULTS: South Asians with family history of CHD were more likely to have diagnosed CHD (odds ratio 1.71 [95% CI 1.21, 2.42]; p = 0.002) and more previous CHD events (regression coefficient 0.44 [0.16, 0.72]; p = 0.002) than those without family history, independent of biological and sociodemographic risk factors. Family history associations with diagnosed CHD/number of events were weaker in Europeans (odds ratio 1.11 [0.78, 1.57]; p = 0.562/regression coefficient 0.02 [-0.25, 0.30]; p = 0.878), largely explained by biological risk factors. South Asians with family history had modestly increased CAC burden compared with Europeans. CONCLUSIONS: There were markedly stronger associations between family history and clinical CHD in South Asians, and a similar trend for subclinical CHD. Early preventive and therapeutic interventions are particularly important in South Asians with a family history of CHD.

9.
Water Res ; 164: 114956, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415966

RESUMO

The aim of this study was to investigate the effect of natural organic matter (NOM) including humic acid (HA) and fulvic acid (FA), intracellular organic matter (IOM) extracted from Microcystis aeruginosa (MA) and Chlorella sp. (CH), and their different molecular weight (MW) fractions on the aerobic denitrification performance of bacterial strain WGX-9 by monitoring nitrogen removal efficiency and testing changes in organic matter with HA, FA, MA-IOM and CH-IOM as the sole carbon source. Strain WGX-9 was identified as Acinetobacter johnsonii and exhibited excellent aerobic denitrification capability. The nitrate removal efficiency with IOM as the sole carbon source was relatively higher than that with NOM as the sole carbon source. The prepared NOM and extracted IOM samples were separated into six fractions with MW cut-offs of 100, 30, 10, 5 and 1 kDa. The fraction of MW > 100 kDa contributed the largest amount to the MW distribution, accounting for 77.11%, 29.00%, 44.97% and 24.81% of HA, FA, MA-IOM, and CH-IOM, respectively. Nitrate removal efficiency was improved with decreasing MW of organic matter. For example, nitrate removal efficiency was 26.50%, 32.41%, 27.88% and 43.89% using HA, FA, MA-IOM, and CH-IOM fractions of MW > 100 kDa as the carbon source, whereas with MW < 1 kDa, it increased to 36.67%, 37.88%, 60.90%, and 68.90%, respectively. This is probably because the smaller MW fraction is more suitable for bacterial growth. These results demonstrate that the strain WGX-9 can utilize lower MW organic matter, which lays the foundations for nitrogen removal in actual drinking water reservoirs.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31394567

RESUMO

There is increasing interest in developing drugs that act at α4ß2 nicotinic acetylcholine receptors (nAChRs) to treat alcohol use disorder. The smoking cessation agent varenicline, a partial agonist of α4ß2 nAChRs, reduces alcohol intake, but its use can be limited by side effects at high therapeutic doses. There are two stoichiometric forms of α4ß2 nAChRs, (α4)3(ß2)2 and (α4)2(ß2)3. Here we investigated the hypothesis that NS9283, a positive allosteric modulator selective for the (α4)3(ß2)2 form, reduces ethanol consumption. NS9283 increased the potency of varenicline to activate and desensitize (α4)3(ß2)2 nAChRs in vitro without affecting other known targets of varenicline. In male and female C57BL/6J mice, NS9283 (10 mg/kg) reduced ethanol intake in a two-bottle choice, intermittent drinking procedure without affecting saccharin intake, ethanol-induced incoordination or ethanol-induced loss of the righting reflex. Subthreshold doses of NS9283 (2.5 mg/kg) plus varenicline (0.1 mg/kg) synergistically reduced ethanol intake in both sexes. Finally, despite having no aversive valence of its own, NS9283 enhanced ethanol-conditioned place aversion. We conclude that compounds targeting the (α4)3(ß2)2 subtype of nAChRs can reduce alcohol consumption, and when administered in combination with varenicline, may allow use of lower varenicline doses to decrease varenicline side effects.

11.
Sensors (Basel) ; 19(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443486

RESUMO

Mobile video applications are becoming increasingly prevalent and enriching the way people learn and are entertained. However, on mobile terminals with inherently limited resources, mobile video streaming services consume too much energy and bandwidth, which is an urgent problem to solve. At present, research on cost-effective mobile video streaming typically focuses on the management of data transmission. Among such studies, some new approaches consider the user's behavior to further optimize data transmission. However, these studies have not adequately discussed the specific impact of the physical environment on user behavior. Therefore, this paper takes into account the environment-aware watching state and proposes a cost-effective mobile video streaming scheme to reduce power consumption and mobile data usage. First, the watching state is predicted by machine learning based on user behavior and the physical environment during a given time window. Second, based on the resulting prediction, a downloading algorithm is introduced based on the user equipment (UE) running mode in the LTE system and the VLC player. Finally, according to the corresponding experimental results obtained in a real-world environment, the proposed approach, compared to its benchmarks, effectively reduces the data usage (14.4% lower than that of energy-aware, on average) and power consumption (about 19% when there are screen touches) of mobile devices.

12.
Nat Plants ; 5(8): 810-821, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31308504

RESUMO

Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.

13.
Ann Bot ; 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-31329816

RESUMO

BACKGROUND AND AIMS: Root system morphology is important for sustainable agriculture, but the genetic basis of root traits and their relationship to shoot traits remain to be elucidated. The aim of the present study was to dissect the genetic basis of root traits at late growth stages and its implications on shoot traits in wheat. METHODS: Among 323 wheat accessions, we investigated phenotypic differences in root traits at booting and mid-grain fill stages in PVC tubes, shoot traits including plant height (PH), canopy temperature (CT) and grain yield per plant (YPP) in a field experiment, and performed a genome-wide association study with a Wheat 660K SNP Array. KEY RESULTS: Deep-rooted accessions had lower CT and higher YPP than those with shallow roots, but no significant relationship was identified between root dry weight and shoot traits. Ninety-three significantly associated loci (SALs) were detected by the mixed linear model, among which three were hub SALs (Co-6A, Co-6B and Co-6D) associated with root depth at both booting and mid-grain fill stages, as well as CT and YPP. Minirhizotron system scanning results suggested that the causal genes in the three SALs may regulate root elongation in the field. The heritable independence between root depth and PH was demonstrated by linkage disequilibrium analysis. The YPP was significantly higher in genotypes which combined favourable marker alleles (FMAs) for root depth and PH, suggesting that a deep root and shorter plant height are suitable traits for pyramiding target alleles by molecular marker-assisted breeding. CONCLUSIONS: These results uncovered promising genomic regions for functional gene discovery of root traits in the late growth period, enhanced understanding of correlation between root and shoot traits, and will facilitate intensive study on root morphology and breeding through molecular design.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31350163

RESUMO

OBJECTIVE: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aß) and Aß transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for Aß, which can prevent plasma Aß from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aß, sLRP1, sRAGE levels. DESIGN: Cross-sectional study. SETTING: The committee office of the village. PARTICIPANTS: Residents lived in the village for more than 3 years, aged 40-85 years (n = 1,119, 63.5% women). MEASUREMENTS: Plasma biomarkers include ApoE genotype, Aß, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. RESULTS: After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of Aß42 was higher and log-transformed sLRP1 was lower in ApoE ε4 carriers than that in noncarriers (ßAß42 = 1.214, 95% confidence interval: 0.105-2.316, pAß42 = 0.031; ßsLRP1 = -0.075, 95% confidence interval: -0.129 to -0.021, psLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aß40 was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (rsLRP1 = 0.116, psLRP1 <0.001; rsRAGE = 0.078, psLRP1 = 0.009, respectively). Plasma Aß42 was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). CONCLUSION: ApoE ε4 carriers had higher plasma Aß42 levels and lower sLRP1 levels. These data indicated that the ApoE ε4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aß42 and sLRP1 levels, but it needs to be further elucidated.

15.
J Oral Rehabil ; 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31175668

RESUMO

Wound healing can be divided into different phases, and timely initiation and cessation of these stages is key to successful wound healing; otherwise, scar tissue forms in the wounded area. Connexins (Cxs) were confirmed to influence scar formation, and Cx43, an indispensable member of the Cx family, was shown to be involved in this process. Our study investigated the regulatory role of Cx43 in scar formation and the possible cell signalling pathways. We established oral mucosa and skin wound healing models in C57BL/6J mice. RT-PCR, western blotting, immunohistochemistry and immunofluorescence were used to examine the expression of ECM components and key proteins in cell signalling pathways (TGF-ß1, Smad2/3, Cx43, Erk1/2 MMP-1 and collagen III). After injury, buccal mucosa wounds healed with no scar, whereas skin wounds healed with an evident scar. Nevertheless, TGF-ß1 expression gradually increased by the 5th day after injury; Cx43 expression showed a similar response, with a progressive increase in the skin and a peak on day 14. In contrast, TGF-ß1 and Cx43 expression in the oral mucosa remained low. The high level of TGF-ß1 increased p-Smad2/3 levels and then induced Cx43, whereas increased expression of Cx43 antagonised the phosphorylation of Erk1/2, a protein downstream of Cx43, which affected MMP-1 synthesis. MMP-1 deficiency led to collagen III accumulation and facilitated scar formation. We demonstrated that TGF-ß1-induced Cx43 promotes scar formation via the Erk/MMP-1/collagen III pathway.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31222412

RESUMO

PURPOSE: Loneliness is an important issue for mental health service users. However, it has not been a particularly prominent focus of recent mental health research. This paper aimed to explore the severity of loneliness among people leaving mental health community crisis services, and to identify factors associated with loneliness. METHODS: A total of 399 participants experiencing mental health crises recruited for a research trial from community crisis services were included in this cross-sectional study. They completed the eight-item measure of the University of California at Los Angeles Loneliness Scale and a set of instruments assessing socio-demographic, psychosocial, and psychiatric variables. RESULTS: Severity of loneliness was high among people leaving community crisis services. Longer years since first contact with mental health services (2-10 years, coefficient = 1.83, 95% CI 0.49-3.16; more than 10 years, coefficient = 1.91, 95% CI 0.46-3.36) and more severe affective symptoms (coefficient = 0.32, 95% CI 0.23-0.40) were associated with greater loneliness, whereas bigger social network size (coefficient = - 0.56, 95% CI - 0.76 to - 0.36) and greater social capital (coefficient = - 0.16, 95% CI - 0.31 to - 0.003) were associated with less severe loneliness. CONCLUSIONS: This paper supports a view that people experiencing mental health crises often report relatively severe loneliness, and that loneliness tends to become more severe during the course of illness. A greater awareness of loneliness among mental health professionals may be beneficial. Loneliness is a potential focus of the development of interventions to improve the lives and outcomes of people with significant mental health problems.

17.
Mol Oncol ; 13(7): 1589-1604, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31162799

RESUMO

Activation of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway induces glial differentiation of glioblastoma (GBM) cells, but the mechanism by which microRNA (miRNA) regulate this process remains poorly understood. In this study, by performing miRNA genomics and loss- and gain-of-function assays in dibutyryl-cAMP-treated GBM cells, we identified a critical negative regulator, hsa-miR-1275, that modulates a set of genes involved in cancer progression, stem cell maintenance, and cell maturation and differentiation. Additionally, we confirmed that miR-1275 directly and negatively regulates the protein expression of glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. Of note, tri-methyl-histone H3 (Lys27) (H3K27me3), downstream of the PKA/polycomb repressive complex 2 (PRC2) pathway, accounts for the downregulation of miR-1275. Furthermore, decreased miR-1275 expression and induction of GFAP expression were also observed in dibutyryl-cAMP-treated primary cultured GBM cells. In a patient-derived glioma stem cell tumor model, a cAMP elevator and an inhibitor of H3K27me3 methyltransferase inhibited tumor growth, induced differentiation, and reduced expression of miR-1275. In summary, our study shows that epigenetic inhibition of miR-1275 by the cAMP/PKA/PRC2/H3K27me3 pathway mediates glial induction of GBM cells, providing a new mechanism and novel targets for differentiation-inducing therapy.

18.
J Integr Plant Biol ; 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31161629

RESUMO

Arabidopsis thaliana CERK1 is an essential receptor-like kinase in the chitin signal transduction pathway. The juxtamembrane (JM) domain of CERK1 regulates the kinase activity of this receptor. Here we demonstrate that the JM domains of LysM-RLKs, CERK1, and OsCERK1 play a functionally conserved role in the activation of chitin signaling in Arabidopsis. The C-termini of the JM domains of both CERK1 and OsCERK1 are indispensable for their function. Moreover, after replacing the JM domain of CERK1 with that of the nonhomologous RLK, BAK1 (CJBa) or FLS2 (CJFl), the chimeric CERK1 receptors maintained their ability to activate chitin signaling in Arabidopsis. Interestingly, the heterologous expression of CJBa and CJFl did not induce cell death in Nicotiana benthamiana leaves. These results suggest that the JM domains of CERK1, BAK1, and FLS2 play a conserved role in chitin signaling via a mechanism not related to sequence homology.

19.
J Biol Chem ; 294(32): 12132-12145, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31221718

RESUMO

Nicotinic acetylcholine receptor (nAChR) ligands that lack agonist activity but enhance activation in the presence of an agonist are called positive allosteric modulators (PAMs). nAChR PAMs have therapeutic potential for the treatment of nicotine addiction and several neuropsychiatric disorders. PAMs need to be selectively targeted toward certain nAChR subtypes to tap this potential. We previously discovered a novel PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which selectively potentiates the opening of α4ß2*, α2ß2*, α2ß4*, and (α4ß4)2α4 nAChRs and reactivates some of these subtypes when desensitized (* indicates the presence of other subunits). We located the Br-PBTC-binding site through mutagenesis and docking in α4. The amino acids Glu-282 and Phe-286 near the extracellular domain on the third transmembrane helix were found to be crucial for Br-PBTC's PAM effect. E282Q abolishes Br-PBTC potentiation. Using (α4E282Qß2)2α5 nAChRs, we discovered that the trifluoromethylated derivatives of Br-PBTC can potentiate channel opening of α5-containing nAChRs. Mutating Tyr-430 in the α5 M4 domain changed α5-selectivity among Br-PBTC derivatives. There are two kinds of α4 subunits in α4ß2 nAChRs. Primary α4 forms an agonist-binding site with another ß2 subunit. Accessory α4 forms an agonist-binding site with another α4 subunit. The pharmacological effect of Br-PBTC depends both on its own and agonists' occupancy of primary and accessory α4 subunits. Br-PBTC reactivates desensitized (α4ß2)2α4 nAChRs. Its full efficacy requires intact Br-PBTC sites in at least one accessory and one primary α4 subunit. PAM potency increases with higher occupancy of the agonist sites. Br-PBTC and its derivatives should prove useful as α subunit-selective nAChR PAMs.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31242548

RESUMO

This research aims to explore the interaction between environmental performance and employment China's manufacturing industries. Based on the environmental performance of 32 industries in China's manufacturing industry during 2006-2015, a panel vector autoregressive model was constructed to study the interaction between industry output and employment in clean industries and dirty industries. The dynamic impact and internal transmission mechanism between environmental performance is analyzed. The study found that in the early stage, due to the reduction of production scale, there was a weak and short-term negative correlation effect on employment, and the mutual promotion relationship between economic benefits and employment was unsustainable. In return, employment affects environmental performance, but the effect differs due to the different forms of environmental performance. For dirty industries, the impact of environmental performance on employment through technical effects is more significant and, thus, a win-win situation of ecological environment and employment stability will be achieved. This research has practical significance regarding how to scientifically and effectively carry out environmental regulation and green management.

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