RESUMEN
We present the first ab initio lattice calculations of spin and density correlations in hot neutron matter using high-fidelity interactions at next-to-next-to-next-to-leading order in chiral effective field theory. These correlations have a large impact on neutrino heating and shock revival in core-collapse supernovae and are encapsulated in functions called structure factors. Unfortunately, calculations of structure factors using high-fidelity chiral interactions were well out of reach using existing computational methods. In this Letter, we solve the problem using a computational approach called the rank-one operator (RO) method. The RO method is a general technique with broad applications to simulations of fermionic many-body systems. It solves the problem of exponential scaling of computational effort when using perturbation theory for higher-body operators and higher-order corrections. Using the RO method, we compute the vector and axial static structure factors for hot neutron matter as a function of temperature and density. The ab initio lattice results are in good agreement with virial expansion calculations at low densities but are more reliable at higher densities. Random phase approximation codes used to estimate neutrino opacity in core-collapse supernovae simulations can now be calibrated with ab initio lattice calculations.
RESUMEN
Ab initio calculations have an essential role in our fundamental understanding of quantum many-body systems across many subfields, from strongly correlated fermions1-3 to quantum chemistry4-6 and from atomic and molecular systems7-9 to nuclear physics10-14. One of the primary challenges is to perform accurate calculations for systems where the interactions may be complicated and difficult for the chosen computational method to handle. Here we address the problem by introducing an approach called wavefunction matching. Wavefunction matching transforms the interaction between particles so that the wavefunctions up to some finite range match that of an easily computable interaction. This allows for calculations of systems that would otherwise be impossible owing to problems such as Monte Carlo sign cancellations. We apply the method to lattice Monte Carlo simulations15,16 of light nuclei, medium-mass nuclei, neutron matter and nuclear matter. We use high-fidelity chiral effective field theory interactions17,18 and find good agreement with empirical data. These results are accompanied by insights on the nuclear interactions that may help to resolve long-standing challenges in accurately reproducing nuclear binding energies, charge radii and nuclear-matter saturation in ab initio calculations19,20.
RESUMEN
Toxocara canis is a parasitic zoonose that is distributed worldwide and is one of the two pathogens causing toxocariasis. After infection, it causes serious public health and safety problems, which pose significant veterinary and medical challenges. To better understand the regulatory effects of T. canis infection on the host immune cells, murine macrophages (RAW264.7) were incubated with recombinant T. canis C-type lectin 4 (rTc-CTL-4) protein in vitro. The quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the nucleotide-binding oligomerization domain-containing protein 1/2 (NOD1/2), receptor-interacting protein 2 (RIP2), nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) on mRNA level and protein expression level in macrophages. Our results indicated that 10 µg/mL rTc-CTL-4 protein could modulate the expression of NOD1, NOD2, and RIP2 at both the transcriptional and translational levels. The protein translation levels of NF-κB, P-p65, p38, and P-p38 in macrophages were also modulated by rTc-CTL-4 protein. Macrophages were co-incubated with rTc-CTL-4 protein after siRNA silencing of NOD1, NOD2, and RIP2. The expression levels of NF-κB, P-p65, p38, and P-p38 were significantly changed compared with the negative control groups (Neg. Ctrl.). Taken together, rTc-CTL-4 protein seemed to act on NOD1/2-RIP2-NF-κB and MAPK signaling pathways in macrophages and might activate MAPK and NF-κB signaling pathways by regulating NOD1, NOD2, and RIP2. The insights from the above studies could contribute to our understanding of immune recognition and regulatory mechanisms of T. canis infection in the host animals.
Asunto(s)
FN-kappa B , Toxocara canis , Animales , Ratones , FN-kappa B/genética , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Toxocara canis/metabolismo , Transducción de Señal/fisiología , MacrófagosRESUMEN
Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.
Asunto(s)
Hipertensión Renal , Nefritis , Humanos , Inflamación , CitocinasRESUMEN
Introduction: Clonal integration of connected ramets within clones is an important ecological advantage. In this study, we tested the hypothesis that the effects of clonal integration on performance of donor and recipient ramets when one resource is heterogeneous can be influenced by the availability of another resource of donor ramets. Methods: We conducted a greenhouse experiment on the widespread, perennial herb Glechoma longituba. Clonal fragments consisting of pairs of connected ramets were grown for seven weeks. The younger, apical ramets were exposed under 30% or 100% light condition and the older, basal ramets were treated with three levels of nutrients. The connections between ramets were either severed or left intact. 30% light condition negatively affected the growth of apical ramets, basal ramets and the whole fragments. Results: Clonal integration significantly increased the growth of apical ramets, but decreased the growth of the basal ramets. Medium and high level nutrient availability of basal ramets significantly increased the growth of apical ramets, basal ramets and the whole fragments. At the high nutrient level, the reduction in growth of basal ramets from clonal integration was decreased, but the growth responses of apical ramets and the whole fragments to clonal integration were not influenced by nutrient availability. Conclusion: The results suggested that clonal integration was benefit to the growth of apical ramets of Glechoma longituba but at the cost of reducing the growth of basal ramets. Although the high nutrient level could reduce the cost that clonal integration brought to the unshaded basal ramets, but could not increase the benefit that clonal integration brought to the shaded apical ramets and whole fragment.
RESUMEN
Biodegradation is commonly employed for remediating trichloroethene- or toluene-contaminated sites. However, remediation methods using either anaerobic or aerobic degradation are inefficient for dual pollutants. We developed an anaerobic sequencing batch reactor system with intermittent oxygen supply for the codegradation of trichloroethylene and toluene. Our results showed that oxygen inhibited anaerobic dechlorination of trichloroethene, but dechlorination rates remained comparable to that at dissolved oxygen levels of 0.2 mg/L. Intermittent oxygenation engendered reactor redox fluctuations (-146 to -475 mV) and facilitated rapid codegradation of targeting dual pollutants, with trichloroethene degradation constituting only 27.5% of the noninhibited dechlorination. Amplicon sequencing analysis revealed the predominance of Dehalogenimonas (16.0% ± 3.5%) over Dehalococcoides (0.3% ± 0.2%), with ten times higher transcriptomic activity in Dehalogenimonas. Shotgun metagenomics revealed numerous genes related to reductive dehalogenases and oxidative stress resistance in Dehalogenimonas and Dehalococcoides, as well as the enrichment of diversified facultative populations with functional genes related to trichloroethylene cometabolism and aerobic and anaerobic toluene degradation. These findings suggested that the codegradation of trichloroethylene and toluene may involve multiple biodegradation mechanisms. Overall results of this study demonstrate the effectiveness of intermittent micro-oxygenation in aiding trichloroethene-toluene degradation, suggesting the potential for the bioremediation of sites with similar organic pollutants.
Asunto(s)
Chloroflexi , Contaminantes Ambientales , Tricloroetileno , Chloroflexi/genética , Chloroflexi/metabolismo , Tricloroetileno/metabolismo , Anaerobiosis , Biodegradación Ambiental , OxígenoRESUMEN
Two novel Gram-stain-negative, aerobic and rod-shaped bacterial strains, designated DHG64T and 4D114T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. DHG64T grew at 12-37 °C (optimum 33 °C), pH 4.5-10.0 (optimum 6.5-7.5) and in the presence of 0-2.0â% NaCl (w/v); while 4D114T grew at 12-37 °C (optimum 20-33 °C), pH 4.0-7.0 (optimum 4.5-6.0) and in the presence of 0-1.0â% NaCl (w/v). DHG64T and 4D114T showed 97.1-98.0 and 97.5-98.4â% 16S rRNA gene sequence similarities with seven species of the genus Trinickia with validly published names, respectively. In the phylogenetic trees based on 16S rRNA gene and genome sequences, both strains formed a clade with the members of genus Trinickia but well separated from each other. The average nucleotide identity and digital DNA-DNA hybridisation values for the novel strains to all species of the genus Trinickia with validly published names were in the ranges of 80.6-85.0 and 22.4-28.0â%, respectively. DHG64T contained C16â:â0, C17â:â0 cyclo and C19â:â0 cyclo ω8c, while 4D114T had C16â:â0, C17â:â0 cyclo, C19â:â0 cyclo ω8c and summed feature 2 (iso-C16â:â1 I and/or C14â:â0 3-OH) as the major cellular fatty acids. The major polar lipids for strains DHG64T and 4D114T were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C contents of DHG64T and 4D114T were 63.0 and 62.8 mol%, respectively. Genomic analyses indicated that DHG64T and 4D114T may have potential for various applications, such as developing drugs against certain health problems and restoring environments polluted with metal ions and/or benzoate. On the basis of the results of morphological, physiological, biochemical and phylogenetic analyses, strains DHG64T and 4D114T were classified as representing two novel species of the genus Trinickia, for which the names Trinickia mobilis sp. nov. (type strain DHG64T = KACC 21223T = GDMCC 1.1282T) and Trinickia acidisoli sp. nov. (type strain 4D114T = KCTC 82876T = GDMCC 1.2131T) are proposed.
Asunto(s)
Burkholderiaceae , Ácidos Grasos , Ácidos Grasos/química , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Cloruro de Sodio , ADN Bacteriano/genética , Análisis de Secuencia de ADN , Composición de Base , Microbiología del Suelo , Técnicas de Tipificación BacterianaRESUMEN
The carbon atom provides the backbone for the complex organic chemistry composing the building blocks of life. The physics of the carbon nucleus in its predominant isotope, 12C, is similarly full of multifaceted complexity. Here we provide a model-independent density map of the geometry of the nuclear states of 12C using the ab initio framework of nuclear lattice effective field theory. We find that the well-known but enigmatic Hoyle state is composed of a "bent-arm" or obtuse triangular arrangement of alpha clusters. We identify all of the low-lying nuclear states of 12C as having an intrinsic shape composed of three alpha clusters forming either an equilateral triangle or an obtuse triangle. The states with the equilateral triangle formation also have a dual description in terms of particle-hole excitations in the mean-field picture.
RESUMEN
Introduction: Chronic hypertension may have a contributory role toward cognitive impairment. Acupuncture exerts protective effects on cognitive functions while controlling the blood pressure. However, the neural mechanism underlying the dual attenuating effect of acupuncture remains unclear. In this study, we investigated the effects of electroacupuncture (EA) and manual acupuncture (MA) on the functional activity of the brain regions of spontaneously hypertensive rats (SHRs) by through resting-state functional magnetic resonance imaging (rs-fMRI). We also evaluated the differences in these functional activities between the EA and MA groups. Methods: We randomly assigned 30 SHRs into the EA, MA, and model (SHR) groups. Wistar Kyoto rats (n = 10) were used as normal control (WKY). The interventions were administered once every alternate day for 12 weeks. The systolic blood pressure of all rats was recorded every 2 weeks until the end of the intervention. After the intervention, rs-fMRI scanning was performed to access the whole brain data of rats randomly selected from each group evenly. The amplitude of low frequency fluctuation (ALFF) analysis, regional homogeneity (ReHo) analysis, and functional connectivity (FC) analysis were also conducted. The Morris water maze (MWM) test was conducted to evaluate the learning and memory of the rats. Hematoxylin-eosin staining and Nissl staining were performed to observe histopathological changes in the key brain regions. Results: We demonstrated that, when compared with the SHR group, the EA and MA groups had significantly lower blood pressure and better performance for behavioral test indices, and that the effect of EA was better than that of MA. ALFF and ReHo analyses revealed enhancement of the neuronal activity of some functionally impaired brain areas in the EA and MA groups. The main callback brain regions included the hypothalamus, entorhinal cortex, brain stem, prelimbic cortex, cingulate cortex, corpus callosum, and cerebellum. The FC analysis demonstrated that EA and MA enhanced the functional connectivity between the seeds and brain regions such as the brain stem, entorhinal cortex, hippocampus, prelimbic cortex, and cerebellum. The pathological test of the entorhinal cortex also verified the protective effect of acupuncture on the neuronal functional activity. Discussion: Our findings suggested that EA and MA exhibited attenuating effects on hypertension and cognitive dysfunction by enhancing the functional activities in the corresponding brain regions. Moreover, EA activated more callback brain regions and functional connectivity than MA, which may explain why the effect of EA was better than that of MA.
RESUMEN
Cytochrome P450 enzymes are promising biocatalysts for industrial use because they catalyze site-selective C-H oxidation and have diverse catalytic reactions and a broad substrate range. In this study, the 2α-hydroxylation activity of CYP154C2 from Streptomyces avermitilis MA-4680T toward androstenedione (ASD) was identified by an in vitro conversion assay. The testosterone (TES)-bound structure of CYP154C2 was solved at 1.42 Å, and this structure was used to design eight mutants, including single, double, and triple mutants, to improve the conversion efficiency. Mutants L88F/M191F and M191F/V285L were found to enhance the conversion rates significantly (i.e., 8.9-fold and 7.4-fold for TES, 46.5-fold and 19.5-fold for ASD, respectively) compared with the wild-type (WT) enzyme while retaining high 2α-position selectivity. The substrate binding affinity of the L88F/M191F mutant toward TES and ASD was enhanced compared with that of WT CYP154C2, supporting the measured increase in the conversion efficiencies. Moreover, the total turnover number and kcat/Km of the L88F/M191F and M191F/V285L mutants increased significantly. Interestingly, all mutants containing L88F generated 16α-hydroxylation products, suggesting that L88 in CYP154C2 plays a vital role in substrate selectivity and that the amino acid corresponding to L88 in the 154C subfamily affects the orientation of steroid binding and substrate selectivity. IMPORTANCE Hydroxylated derivatives of steroids play essential roles in medicine. Cytochrome P450 enzymes selectively hydroxylate methyne groups on steroids, which can dramatically change their polarity, biological activity and toxicity. There is a paucity of reports on the 2α-hydroxylation of steroids, and documented 2α-hydroxylate P450s show extremely low conversion efficiency and/or low regio- and stereoselectivity. This study conducted crystal structure analysis and structure-guided rational engineering of CYP154C2 and efficiently enhanced the conversion efficiency of TES and ASD with high regio- and stereoselectivity. Our results provide an effective strategy and theoretical basis for the 2α-hydroxylation of steroids, and the structure-guided rational design of P450s should facilitate P450 applications in the biosynthesis of steroid drugs.
Asunto(s)
Sistema Enzimático del Citocromo P-450 , Esteroides , Hidroxilación , Esteroides/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Oxidación-Reducción , Testosterona/metabolismo , Especificidad por SustratoRESUMEN
Purpose: Mutation in the USH2A gene is the most common cause of inherited retinal dystrophy (IRD), including non-syndromic retinitis pigmentosa (RP) and Usher syndrome II (USH2). Gene editing and therapy targeting USH2A, especially the hotspot region, would benefit a large proportion of IRD patients. In this study, we comprehensively analyzed the genetic spectrum of the USH2A gene, aiming to identify global hot spot mutations in USH2A-related IRDs and differences in hot spot regions across continents. Materials and methods: A retrospective USH2A-related IRD study was conducted, including our IRD cohort, and reported USH2A studies worldwide. Results: A total of 3,972 mutated USH2A alleles of approximately 1,935 patients were collected from 33 cohort studies worldwide, containing 102 alleles of 51 patients in our IRD cohort. Mutations in exon 13 were the most common, reaching 18.4% globally and a higher frequency of 22% in America, 19.2% in Europe, and a lower 12% in East Asia. Pathogenic mutations that affected 10 of the 72 exons of USH2A, exon 2, exon 13, exon 41-43, exon 50, exon 54, exon 57, exon 61, and exon 63 in total were responsible for half of global USH2A mutant alleles. With base editors including adenine base editor (ABE), cytidine base editor (CBE), and glycosylase base editor (GBE), 76.3% of single nucleotide variations (SNVs) and 58% of all mutations in USH2A are correctable. Meantime, four novel pathogenic mutations were revealed in our IRD cohort, p. (Val1130Cysfs*72), p. (Ala2139fs*14), p. (Gly4139Arg), and p. (Val4166Cysfs*7). Conclusion: In this study, we revealed four novel mutations, expanding the spectrum of USH2A mutations, and importantly presented global hotspot exons and mutations of USH2A as well as the proportion of SNVs that can be restored by different base editors, providing a perspective for exploring high-efficiency and broader-reaching gene editing and gene therapies.
RESUMEN
While first order perturbation theory is routinely used in quantum Monte Carlo (QMC) calculations, higher-order terms present significant numerical challenges. We present a new approach for computing perturbative corrections in projection QMC calculations. We demonstrate the method by computing nuclear ground state energies up to second order for a realistic chiral interaction. We calculate the binding energies of several light nuclei up to ^{16}O by expanding the Hamiltonian around the Wigner SU(4) limit and find good agreement with data. In contrast to the natural ordering of the perturbative series, we find remarkably large second-order energy corrections. This occurs because the perturbing interactions break the symmetries of the unperturbed Hamiltonian. Our method is free from the sign problem and can be applied to QMC calculations for many-body systems in nuclear physics, condensed matter physics, ultracold atoms, and quantum chemistry.
RESUMEN
Rice (Oryza sativa L.) is an important crop worldwide. Functional rice has exhibited health benefits. The aim of this study was to use marker-assisted selection (MAS) to introgress two genes, GE (giant embryo) and OsALDH7 (aldehyde dehydrogenase, golden-like endosperm) into colored rice and obtain high yield functional rice. CNY103108 and CNY103107 are two rice lines with golden-like endosperms and giant embryos. They were used as the donor parents. CNY922401, an elite purple waxy rice line, and TNGSW26, an indica red waxy rice cultivar were used as the recurrent parents. Foreground selection of the progenies was completed using functional markers for GE and OsALDH7, and background selection was completed using molecular markers to recover the background of the recurrent parents. MAS results showed a purple functional rice population (PFR) (CNY922401/CNY103108), with the recovery rate of the recurrent parental genome as 91.3%, and a red functional rice population (RFR) (TNGSW26/CNY103107) with the recovery as 89.8%. After five-season yield trials and several antioxidant activities analyses, PFR32 and RFR13 lines, which have similar yields and antioxidant activities, were selected as the recurrent parents with a golden-like endosperm and a giant embryo. For a biofortification purpose, they can become valuable products and be adapted to the current agricultural community.
Asunto(s)
Oryza , Agricultura , Antioxidantes , Marcadores Genéticos , Oryza/genética , Fitomejoramiento/métodosRESUMEN
Cytochrome P450 enzymes (CYPs or P450s) are ubiquitous heme-dependent enzymes that catalyze the monooxygenation of non-activated C-H bonds to modify the structure of the substrate. In this study, we heterologously expressed CYP107X1 from Streptomyces avermitilis and conducted inâ vitro substrate screening using the alternative redox partners putidaredoxin and putidaredoxin reductase. CYP107X1 catalyzed the 16α-hydroxylation of progesterone with regio- and stereoselectivity. The spectroscopic analyses showed that CYP107X1 bound progesterone with a relatively high Kd value of 65.3±38.9â µM. The Km and kcat values for progesterone were estimated to be 47.7±12.0â µM and 0.30â min-1 , respectively. Furthermore, a crystal structure was obtained of CYP107X1 bound with glycerol from the buffer solution. Interestingly, a conserved threonine was replaced with asparagine in CYP107X1, indicating that it may adopt an unnatural proton transfer process and play a crucial role in its catalytic activity.
Asunto(s)
Progesterona , Streptomyces , Sistema Enzimático del Citocromo P-450/metabolismo , Hidroxilación , Progesterona/metabolismo , Streptomyces/metabolismoRESUMEN
Studies on rodents and nonhuman primates suggest that exposure to anesthetics, particularly in the young brain, is associated with neuronal apoptosis as well as hippocampaldependent cognitive dysfunction. Disruption of the development of dentate gyrus may play an important role in anestheticsinduced neurotoxicity. However, the anesthetics triggered molecular events in the dentate gyrus of the developing brain are poorly understood. By integrating two independent data sets obtained from miRNAseq and mRNAseq respectively, this study aims to profile the network of miRNA and potential target genes, as well as relevant events occurring in the dentate gyrus of isoflurane exposed 7dayold mice. We found that a single four hours exposure to isoflurane yielded 1059 pairs of differently expressed miRNAs/target genes in the dentate gyrus. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further indicates that dysregulated miRNAs/target genes have farreaching effects on the cellular pathophysiological events, such as cell apoptosis, axon development, and synaptic transmission. Our results would greatly broaden our functional understanding of the role of miRNA/target gene in the context of anestheticsinduced neurotoxicity.
Asunto(s)
Anestésicos , Isoflurano , MicroARNs , Anestésicos/farmacología , Animales , Giro Dentado , Hipocampo , Isoflurano/toxicidad , Ratones , MicroARNs/genéticaRESUMEN
OBJECTIVE: To determine whether singleton pregnancy achieved after preimplantation genetic testing (PGT) is associated with a higher risk of adverse perinatal outcomes than in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) singleton pregnancy. DESIGN: A retrospective cohort study. SETTING: A university-affiliated fertility center. PATIENT(S): This cohort study included singleton live births resulting from PGT (n = 232) and IVF/ICSI singleton pregnancies (n = 2,829) with single frozen-thawed blastocyst transfer. Multiple baseline covariates were used for propensity score matching, yielding 214 PGT singleton pregnancies matched to 617 IVF/ICSI singleton pregnancies. INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): The primary outcome was gestational hypertension, and various clinical perinatal secondary outcomes related to maternal and neonatal health were measured. RESULT(S): Compared with IVF/ICSI singleton pregnancy, PGT singleton pregnancy was associated with a significantly higher risk of gestational hypertension (adjusted odds ratio, 2.58; 95% confidence interval, 1.32, 5.05). In the matched sample, the risk of gestational hypertension remained higher with PGT singleton pregnancy (odds ratio, 2.33; 95% confidence interval, 1.04, 5.22) than with IVF/ICSI singleton pregnancy. No statistical differences were noted in any other measured outcomes between the groups. CONCLUSION(S): The perinatal outcomes of PGT and IVF/ICSI singleton pregnancies were similar except for the observed potentially higher risk of gestational hypertension with PGT singleton pregnancy. However, because the data on PGT singleton pregnancies are limited, this conclusion warrants further investigation.
Asunto(s)
Criopreservación/tendencias , Transferencia de Embrión/tendencias , Pruebas Genéticas/tendencias , Nacimiento Vivo/epidemiología , Diagnóstico Preimplantación/tendencias , Puntaje de Propensión , Adulto , Estudios de Cohortes , Criopreservación/métodos , Transferencia de Embrión/métodos , Femenino , Fertilización In Vitro , Congelación , Pruebas Genéticas/métodos , Humanos , Hipertensión Inducida en el Embarazo/diagnóstico , Hipertensión Inducida en el Embarazo/epidemiología , Recién Nacido , Masculino , Embarazo , Diagnóstico Preimplantación/métodos , Estudios RetrospectivosRESUMEN
A Gram-stain-negative, aerobic, chemoheterotrophic and rod-shaped strain, designated as C5T, was isolated from intertidal surface seawater in Taizhou, Zhejiang Province, PR China and characterized using a polyphasic taxonomic approach. Strain C5T could produce carotenoids and bacteriochlorophyll a. Growth was observed at 20-45 °C, at pH 6.0-9.0 and with 0-8.0â% (w/v) NaCl. The 16S rRNA gene sequence identity analysis revealed that strain C5T was the most closely related to Qipengyuania nanhaisediminis CGMCC 1.7715T (98.8%) and Erythrobacter litoralis DSM 8509T (98.7%). The phylogenetic reconstruction based on core genes demonstrated that strain C5T was clustered into the members of the genus Erythrobacter. The average nucleotide identity and digital DNA-DNA hybridization values between strain C5T and Erythrobacter type strains were lower than 76 and 25â%, respectively. The predominant and minor respiratory quinones were identified as ubiquinone-10 and ubiquinone-9. The major fatty acids were summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c) and iso-C18â:â0. Polar lipids included phosphatidylethanolamine, phosphatidylglycerol, a glycosphingolipid and an unidentified aminolipid. Based on the genetic, chemotaxonomic and phenotypic data, strain C5T is concluded to represent a novel species in the genus Erythrobacter, for which the name Erythrobacter aurantius sp. nov. is proposed. The type strain is C5T (=MCCC 1K05108T=KCTC 92307T).
Asunto(s)
Ácidos Grasos , Sphingomonadaceae , Ácidos Grasos/química , Fosfolípidos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Composición de Base , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Agua de MarRESUMEN
OBJECTIVE: To elucidate the mechanisms of 4 effective components from a Chinese medicine formula, namely Qingre Huoxue Jiedu Formula (QHJ heat- and toxin-clearing and blood-activating formula), in the treatment of nerve growth factor (NGF)-induced psoriasis. METHODS: Keratinocyte proliferation and T cell proliferation models were developed using NGF. An NGF solution (NGF+DMEM, 100 ng/mL) was added to all induced groups and treated groups and were cultured for 24 h, while a solution with NTRK1 antagonist (K252a+DEME, 300 nmol/L) was added and cultured for 1 h. The models were used to evaluate the effects of the treatment with each of the 4 components of QHJ, namely shikonin, paeonol, astilbin and ursolic acid. Cell apoptosis and proliferation were measured by flow cytometry analysis and CCK8 assay, respectively. The mRNA expression levels of Bax, Bcl-xl, and NGF receptor (NGFR) were assessed by quantitative real-time PCR (qRT-PCR) and Western blot analysis, respectively. RESULTS: (1) All QHJ-treated groups showed significantly increased cell apoptosis and inhibition of cell proliferation compared with the NGF-induced groups (P<0.05). In addition, treatment with QHJ plus NTRK1 significantly enhanced cell apoptosis and inhibition of cell proliferation compared with cells treated with QHJ only (P<0.05), particularly in cells treated with ursolic acid. (2) QHJ-treated groups showed higher protein expression levels of Bax, Bcl-xl compared with other groups (P<0.05). Additionally, treatment with QHJ plus NTRK1 significantly increased the protein expression levels of Bax, Bcl-xl and NGFR compared with those treated with QHJ only (all P<0.05), especially in those treated with shikonin. CONCLUSION: The action mechanism of QHJ on psoriasis might be through enhancing cell apoptosis and inhibition of cell proliferation, and upregulating the expression level of Bax, Bcl-xl and NGFR.
Asunto(s)
Medicamentos Herbarios Chinos , Psoriasis , Apoptosis , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Factor de Crecimiento Nervioso/metabolismo , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológicoRESUMEN
In temporal lobe epilepsy (TLE), abnormal axon guidance and synapse formation lead to sprouting of mossy fibers in the hippocampus, which is one of the most consistent pathological findings in patients and animal models with TLE. Glypican 4 (Gpc4) belongs to the heparan sulfate proteoglycan family, which play an important role in axon guidance and excitatory synapse formation. However, the role of Gpc4 in the development of mossy fibers sprouting (MFS) and its underlying mechanism remain unknown. Using a pilocarpine-induced mice model of epilepsy, we showed that Gpc4 expression was significantly increased in the stratum granulosum of the dentate gyrus at 1 week after status epilepticus (SE). Using Gpc4 overexpression or Gpc4 shRNA lentivirus to regulate the Gpc4 level in the dentate gyrus, increased or decreased levels of netrin-1, SynI, PSD-95, and Timm score were observed in the dentate gyrus, indicating a crucial role of Gpc4 in modulating the development of functional MFS. The observed effects of Gpc4 on MFS were significantly antagonized when mice were treated with L-leucine or rapamycin, an agonist or antagonist of the mammalian target of rapamycin (mTOR) signal, respectively, demonstrating that mTOR pathway is an essential requirement for Gpc4-regulated MFS. Additionally, the attenuated spontaneous recurrent seizures (SRSs) were observed during chronic stage of the disease by suppressing the Gpc4 expression after SE. Altogether, our findings demonstrate a novel control of neuronal Gpc4 on the development of MFS through the mTOR pathway after pilocarpine-induced SE. Our results also strongly suggest that Gpc4 may serve as a promising target for antiepileptic studies.
Asunto(s)
Glipicanos/biosíntesis , Fibras Musgosas del Hipocampo/metabolismo , Pilocarpina/toxicidad , Transducción de Señal/fisiología , Estado Epiléptico/metabolismo , Serina-Treonina Quinasas TOR/biosíntesis , Animales , Células Cultivadas , Glipicanos/antagonistas & inhibidores , Masculino , Ratones , Fibras Musgosas del Hipocampo/efectos de los fármacos , Agonistas Muscarínicos/toxicidad , Transducción de Señal/efectos de los fármacos , Estado Epiléptico/inducido químicamente , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
Three yellow-pigmented, Gram-stain-negative, aerobic, motile by flagella and rod-shaped strains, designated as MCT, PC and RC, were isolated from stems of Populus euphratica. Growth of those three strains occurs at 4-40 °C, pH 6.0-10.0 and with 0.5-18.0% (w/v) NaCl. Respiratory quinones contained ubiquinone-9 and ubiquione-8 as major and minor components, respectively. Major fatty acids (> 10%) were summed feature 8 (C18:1ω6c and/or C18:1ω7c), summed feature 3 (C16:1ω6c and/or C16:1ω7c) and C16:0. Polar lipids included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified phospholipids, one unidentified aminolipid, one unidentified glycolipid and four unidentified lipids. Strains MCT, PC and RC shared pairwise 16S rRNA gene sequence similarities of 99.9-100.0%, and showed higher similarities of 98.4-98.5% with Halomonas songnenensis NEAU-ST10-39T and 98.3-98.4% with Halomonas nanhaiensis YIM M 13059T than to other Halomonas type strains. Genomic comparisons revealed that those three strains had the pan-genome consisting of 4446 orthologous clusters, among which 676 orthologous clusters were absent in other Halomonas type strains. Phylogenomic tree indicated that strains MCT, PC and RC formed an independently stable clade with Halomonas nanhaiensis YIM M 13059T and Halomonas songnenensis NEAU-ST10-39T. The average nucleotide identity and digital DNA-DNA hybridization values between those three strains and other Halomonas type strains were < 89.9% and < 39.3%, respectively. Based upon phenotypic, chemotaxonomic, phylogenetic and genomic results, strains MCT, PC and RC represent a novel species in the genus Halomonas, for which the name Halomonas populi sp. nov. is proposed. The type strain is MCT (= JCM 33545T = MCCC 1K03942T).