ε-聚赖氨酸抑菌性能的研究进展

ε-聚赖氨酸(ε-poly-L-lysine,ε-PL)是抑菌谱广泛的天然抑菌剂,由通过α-羧基与ε-氨基连接的25–35个赖氨酸聚合而成。ε-PL主要由白色链霉菌发酵生产所得,比化学生产更加高效和环保。ε-PL具有水溶性好、耐热和对环境无污染等特点,具有良好的应用前景。本文从发酵生产入手,着重综述了ε-PL对各种微生物抑菌性能、抑菌机制及抑菌机制模型的研究进展。推测ε-PL是通过对细胞膜的破坏而改变细胞的通透性,或者作用到细胞内引起活性氧(reactive oxygen species, ROS)胁迫而影响调节基因的表达,从而起到抑菌作用。根据这2种抑菌方式分别建立了相应的抑菌模型,即毡毯模型和ROS诱导细胞凋亡模型。本文可为ε-PL对微生物抑制性能的深入研究提供依据,同时也提出了ε-PL抑菌机制的新模型,为扩展ε-PL应用领域提供了一定的参考。     

Checkpoint-independent stabilization of kinetochore-microtubule attachments by Mad2 in human cells

Faithful chromosome segregation is required for cell and organism viability and relies on both the mitotic checkpoint and the machinery that corrects kinetochore-microtubule (k-MT) attachment errors. Most solid tumors have aneuploid karyotypes and many missegregate chromosomes at high rates in a phenomenon called chromosomal instability (CIN). Mad2 is essential for mitotic checkpoint function and is frequently overexpressed in human tumors that are CIN. For unknown reasons, cells overexpressing Mad2 display high rates of lagging chromosomes. Here, we explore this phenomenon and show that k-MT attachments are hyperstabilized by Mad2 overexpression and that this undermines the efficiency of correction of k-MT attachment errors. Mad2 affects k-MT attachment stability independently of the mitotic checkpoint because k-MT attachments are unaltered upon Mad1 depletion and Mad2 overexpression hyperstabilizes k-MT attachments in Mad1-deficient cells. Mad2 mediates these effects with Cdc20 by altering the centromeric localization and activity of Aurora B kinase, a known regulator of k-MT attachment stability. These data reveal a new function for Mad2 to stabilize k-MT attachments independent of the checkpoint and explain why Mad2 overexpression increases chromosome missegregation to cause chromosomal instability in human tumors.     

Distinct lung microbial community states in patients with pulmonary tuberculosis

An improved understanding of the lung microbiome may lead to better strategies to diagnose, treat, and prevent pulmonary tuberculosis(PTB). However, the characteristics of the lung microbiomes of patients with TB remain largely undefined. In this study, 163 bronchoalveolar lavage(BAL) samples were collected from 163 sputum-negative suspected PTB patients. Furthermore, 12 paired BAL samples were obtained from 12 Mycobacterium tuberculosis-positive(MTB+) patients before and after negative conversion following a two-month anti-TB treatment. The V3–V4 region of the 16 S ribosomal RNA(rRNA) gene was used to characterize the microbial composition of the lungs. The results showed that the prevalence of MTB in the BAL samples was 42.9%(70/163) among the sputum-negative patients. The α-diversity of lung microbiota was significantly less diverse in MTB+ patients compared with Mycobacterium tuberculosis-negative(MTB–) patients. There was a significant difference in β-diversity between MTB+ and MTB– patients. MTB+ patients were enriched with Anoxybacillus, while MTB– patients were enriched with Prevotella, Alloprevotella, Veillonella, and Gemella. There was no significant difference between the Anoxybacillus detection rates of MTB+ and MTB– patients. The paired comparison between the BAL samples from MTB+ patients and their negative conversion showed that BAL negative-conversion microbiota had a higher α-diversity. In conclusion, distinct features of airway microbiota could be identified between samples from patients with and without MTB. Our results imply links between lung microbiota and different clinical groups of active PTB.     

Effect of low sulfate concentrations on lactate oxidation and isotope fractionation during sulfate reduction by Archaeoglobus fulgidus strain Z

The effect of low substrate concentrations on the metabolic pathway and sulfur isotope fractionation during sulfate reduction was investigated for Archaeoglobus fulgidus strain Z. This archaeon was grown in a chemostat with sulfate concentrations between 0.3 mM and 14 mM at 80 degrees C and with lactate as the limiting substrate. During sulfate reduction, lactate was oxidized to acetate, formate, and CO2. This is the first time that the production of formate has been reported for A. fulgidus. The stoichiometry of the catabolic reaction was strongly dependent on the sulfate concentration. At concentrations of more than 300 microM, 1 mol of sulfate was reduced during the consumption of 1 mol of lactate, whereas only 0.6 mol of sulfate was consumed per mol of lactate oxidized at a sulfate concentration of 300 microM. Furthermore, at low sulfate concentrations acetate was the main carbon product, in contrast to the CO2 produced at high concentrations. We suggest different pathways for lactate oxidation by A. fulgidus at high and low sulfate concentrations. At about 300 microM sulfate both the growth yield and the isotope fractionation were limited by sulfate, whereas the sulfate reduction rate was not limited by sulfate. We suggest that the cell channels more energy for sulfate uptake at sulfate concentrations below 300 to 400 microM than it does at higher concentrations. This could explain the shift in the metabolic pathway and the reduced growth yield and isotope fractionation at low sulfate levels.     

Involvement of Presynaptic Histamine H3 Receptors in the Modulation of Somatostatin Binding and Its Effects on Adenylyl Cyclase Activity in the Rat Frontoparietal Cortex

Abstract: Thioperamide (2 mg/kg, i.p.), a histamine H₃-receptor antagonist, increased the number of somatostatin (SS) receptors, with no change in the affinity constant, in the rat frontoparietal cortex. This effect was prevented by treatment with ( R )-α-methylhistamine (3.2 mg/kg, i.p.), a histamine H₃-receptor agonist. Thioperamide also induced an increase in SS binding in rats pretreated with mepyramine, a histamine H₁-receptor antagonist, or cimetidine, a histamine H₂-receptor antagonist. Pretreatment with mepyramine plus cimetidine administered simultaneously antagonized the thioperamide effect on SS binding. The increase in the number of SS receptors was accompanied by a greater SS-mediated inhibition of basal and forskolin-stimulated adenylyl cyclase (AC) activity in frontoparietal cortical membranes in the thioperamide group. Furthermore, the functional activity of the guanine nucleotide-binding inhibitory protein (G_i protein) was not altered by thioperamide or ( R )-α-methylhistamine administration in frontoparietal cortical membranes. In rats treated with mepyramine plus thioperamide or cimetidine plus thioperamide, the increase in the number of SS receptors was also accompanied by an increased SS inhibition of AC activity. Thioperamide induced a significant increase in SS-like immunoreactivity content in the frontoparietal cortex. Altogether, these results suggest that frontoparietal cortical histamine may play, at least in part, a role in the regulation of the somatostatinergic system.     

Temporal and spatial dynamics of grapevine anthracnose and its relationship to pathogen survival

Anthracnose, caused by Elsinoë ampelina, is an economically important grapevine disease in south and southeast Brazil. Control is achieved by lime sulphur application during grapevine dormancy and foliar fungicide sprays until the berries are half-grown. This study assessed the temporal and spatial progress of grapevine anthracnose under field conditions in order to describe the disease dynamics and its relationship to pathogen survival. The experiment was carried out in a vineyard of table grape Vitis labrusca in Brazil, during the 2014 and 2015 growing seasons. The incidence of vines with diseased leaves, stems and berries and the disease severity on leaves were recorded from bud break to veraison. Monomolecular, logistic and Gompertz models were fitted by non-linear regression to the incidence and severity data over time to characterize the temporal progress. Ordinary runs, dispersion index, modified Taylor's power law and spatial hierarchy analyses were used to characterize the spatial pattern of diseased plants. The monomolecular model showed the best fit for the incidence progress, with disease progress rates ranging from 0.051 to 0.136 per day. In both seasons, the incidence of diseased plants reached 100% 1 month after bud break. However, the incidence of diseased leaves per plant was around 60% and leaf disease severity was lower than 5% for both years. Ordinary runs and dispersion index analyses revealed that diseased grapevines were distributed randomly on the majority of the assessment dates. Meanwhile, a slight aggregation of diseased vines was observed in the modified Taylor's power law analysis. Our results suggested that the progress of anthracnose incidence and severity over time was governed mainly by the income of the primary inoculum, which survived in the vineyard. Therefore, anthracnose control measures in Brazilian vineyards should be focused on the reduction in inoculum within the vineyard.     

School start time influences melatonin and cortisol levels in children and adolescents – a community-based study

School start time influences sleep parameters. Differences between circadian sleep parameters on weekends and weekdays have been associated with obesity, sleep, and psychiatric disorders. Moreover, circadian rhythm dysregulation affects the secretion of some hormones, such as melatonin and cortisol. In the current study, we investigate the effect of school start time on cortisol and melatonin levels in a community sample of Brazilian children and adolescents. This was a cross-sectional study of 454 students (mean age, 12.81 ± 2.56 years; 58.6% female). From this sample, 80 participants were randomly selected for saliva collection to measure melatonin and cortisol levels. Circadian sleep parameters were assessed by self-reported sleep and wake up schedules and the Morningness–Eveningness Questionnaire. The outcomes, salivary melatonin and cortisol levels, were measured in morning, afternoon and night saliva samples, and behavior problems were assessed using the Child Behavior Checklist (CBCL). The main results revealed that morning school start time decreased the secretion of melatonin. Morning melatonin levels were significantly positively correlated with the sleep midpoint on weekdays and on weekends. Afternoon melatonin levels were positively correlated with the sleep midpoint on weekends in the morning school students. Conversely, in the afternoon school students, night melatonin levels were negatively correlated with the sleep midpoint on weekdays. Cortisol secretion did not correlate with circadian sleep parameters in any of the school time groups. In conclusion, school start time influences melatonin secretion, which correlated with circadian sleep parameters. This correlation depends on the presence of psychiatric symptoms. Our findings emphasize the importance of drawing attention to the influence of school start time on the circadian rhythm of children and adolescents.