氚水在模拟水生－陆生生态系中的迁移与分布

利用同位素示踪技术研究了进入水体的ＨＴＯ向陆地的迁移。结果表明：１．进入水体的ＨＴＯ将向系统各组分转移,池水中的ＨＴＯ单调地减少,底泥及水生生物中的ＨＴＯ浓度皆在经历某一最大值后平缓地下降;２．ＨＴＯ中的而以自由水沉和结合态氚存在于水生动植物和底泥中;３．ＨＴＯ还明显地向毗邻的陆地和作物迁移,在一个半月期间,陆地系统中的总而约占水体的２４％。     

Platycodin D,a bioactive component of Platycodon grandiflorum,induces cancer cell death associated with extreme vacuolation

Platycodin D (PD) is a major active component of the roots of Platycodon grandiflorum (Jacq.) A.DC. and possesses multiple biological and pharmacological properties, including anti-cancer activity. The aim of this study was to characterize PD-induced cytoplasmic vacuolation in human cancer cells and investigate the underlying mechanisms. PD-induced cancer cell death was associated with cytoplasmic pinocytic and autophagic vacuolation. Cellular energy levels were decreased by this compound, leading to the activation of AMP-activated protein kinase (AMPK). Additionally, compound C, an inhibitor of AMPK, completely prevented PD-induced vacuolation. These results suggest that PD induces cancer cell death, associated with excessive vacuolation through AMPK activation when cellular energy levels are low. Therefore, our findings provide a mechanistic rationale for a novel combinatorial approach using PD to treat cancer.     

Assessment of the restoration of a degraded semi-humid evergreen broadleaf forest ecosystem by combined single-indicator and comprehensive model method

We conducted a long-term restoration experiment in the degraded ecosystems of a semi-humid evergreen broadleaf forest in Muding County, Yunan Province, China. We used single-indicator assessment and our newly established comprehensive assessment model to compare the effects of four types of management (different historical disturbances + restoration measures) on forest restoration based on a vegetation survey. (1) Species richness in each of the four restoring communities was still lower than that of the zonal forest. There was a compensatory effect of species richness among different layers within communities. Restoration management by natural succession was clearly efficient at restoring species richness and composition, but the effect of disturbance history was minor. Human-assisted restoration had a great effect on biomass accumulation and model tree growth. Plant density was also affected by the different management types, which progressively led to differences in model tree growth and biomass accumulation. (2) The comprehensive assessment model, a simple method based on the restoration mechanism, can precisely quantify the overall restoration of ecosystems, historical disturbance and actual disturbance, using only one set of data. Restoration index (R_d), turning-point restoration index (R₀), restoration-effect index (R_a), turning-point disturbance index (D₀), actual disturbance index (D_r) and overcoming disturbance index (D_a) presented gradual changes in the four restoring communities. The combined single-indicator and comprehensive model method fully assessed the restoration of degraded ecosystems in a semi-humid evergreen broadleaf forest.     

Glucocorticoid sensitivity of interleukin-1 agonist and antagonist secretion: the effects of age and gender

Interleukin-1 (IL-1) is a primary mediator of inflammation that is regulated, in part, by the hypothalamic-pituitary-adrenal axis. The purpose of this study was to determine if gender- or age-related differences exist in the sensitivity of IL-1-producing cells to hydrocortisone. Peripheral blood mononuclear cells (PBMC) isolated from men and women (21-77 yr old) were incubated with hydrocortisone (0, 50, 100, 500, or 1,000 ng/ml) with or without lipopolysaccharide (LPS). Secretion of IL-1beta and IL-1 receptor antagonist was inhibited in a dose-dependent manner (P = 0.001) without age- or gender-related differences. Hydrocortisone decreased soluble IL-1 receptor type II (sIL-1RII) secretion by unstimulated cells (P = 0. 0001), but it increased secretion by LPS-stimulated cells (P = 0. 0001) in all groups. Unstimulated cell supernatants from men contained greater concentrations of sIL-1RII than the supernatants from women (P = 0.011). Compared with men, PBMCs from women were less responsive to hydrocortisone inhibition of sIL-1RII secretion, regardless of age (P = 0.001), and compared with the follicular phase, sIL-1RII secretion was lower in the luteal phase of the menstrual cycle (P < 0.05). These data indicate that basal secretion and glucocorticoid modulation of sIL-1RII secretion by cultured PBMCs are gender dependent. Moreover, glucocorticoid influences on sIL-1RII secretion depend on the presence or absence of gram-negative bacterial toxins.     

Consistent Inhibition of Cyclooxygenase Drives Macrophages towards the Inflammatory Phenotype

Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX) inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-derived macrophage culture and long-term COX inhibitor treatments in BALB/c mice and zebrafish, we showed that chronic COX inhibition drives macrophages into an inflammatory state. Macrophages differentiated in the presence of SC-560 (COX-1 inhibitor), NS-398 (COX-2 inhibitor) or indomethacin (COX-1/2 inhibitor) for 7 days produced more TNFα or IL-12p70 with enhanced p65/IκB phosphoylation. YmI and IRF4 expression was reduced significantly, indicative of a more inflammatory phenotype. We further observed that indomethacin or NS-398 delivery accelerated zebrafish death rates during LPS induced sepsis. When COX inhibitors were released over 30 days from an osmotic pump implant in mice, macrophages from peritoneal cavities and adipose tissue produced more TNFα in both the basal state and under LPS stimulation. Consequently, indomethacin-exposed mice showed accelerated systemic inflammation after LPS injection. Our findings suggest that macrophages exhibit a more inflammatory phenotype when COX activities are chronically inhibited.     

IDI2, a second isopentenyl diphosphate isomerase in mammals

We recently described the identification of a novel isopentenyl diphosphate isomerase, IDI2 in humans and mice. Our current data indicate that, in humans, IDI2 is expressed only in skeletal muscle. Expression constructs of human IDI2 in Saccharomyces cerevisiae can complement isomerase function in an idi1-deficient yeast strain. Furthermore, IDI2 has the ability to catalyze the isomerization of [(14)C]IPP to [(14)C]DMAPP. Enzyme kinetic analysis of partially purified IDI2 demonstrate the novel isozyme has a maximal relative specific activity of 1.2 x 10(-1) +/- 0.3 micromol min(-1) mg(-1) at pH 8.0 with a K(IPP)(m) value of 22.8 microm IPP. Both isozymes, IDI1 and IDI2 are localized to the peroxisome by a PTS1-dependent pathway. Finally, our data suggest that IDI2 is regulated independently from IDI1, by a mechanism that may involve PPARalpha.     

The role of phase shifts of sensory inputs in walking revealed by means of phase reduction

Detailed neural network models of animal locomotion are important means to understand the underlying mechanisms that control the coordinated movement of individual limbs. Daun-Gruhn and Tóth, Journal of Computational Neuroscience 31(2), 43–60 (2011) constructed an inter-segmental network model of stick insect locomotion consisting of three interconnected central pattern generators (CPGs) that are associated with the protraction-retraction movements of the front, middle and hind leg. This model could reproduce the basic locomotion coordination patterns, such as tri- and tetrapod, and the transitions between them. However, the analysis of such a system is a formidable task because of its large number of variables and parameters. In this study, we employed phase reduction and averaging theory to this large network model in order to reduce it to a system of coupled phase oscillators. This enabled us to analyze the complex behavior of the system in a reduced parameter space. In this paper, we show that the reduced model reproduces the results of the original model. By analyzing the interaction of just two coupled phase oscillators, we found that the neighboring CPGs could operate within distinct regimes, depending on the phase shift between the sensory inputs from the extremities and the phases of the individual CPGs. We demonstrate that this dependence is essential to produce different coordination patterns and the transition between them. Additionally, applying averaging theory to the system of all three phase oscillators, we calculate the stable fixed points - they correspond to stable tripod or tetrapod coordination patterns and identify two ways of transition between them.     

Protein S-glutathionylation induced by hypoxia increases hypoxia-inducible factor-1α in human colon cancer cells

Hypoxia is a common characteristic of many types of solid tumors. Intratumoral hypoxia selects for tumor cells that survive in a low oxygen environment, undergo epithelial–mesenchymal transition, are more motile and invasive, and show gene expression changes driven by hypoxia-inducible factor-1α (HIF-1α) activation. Therefore, targeting HIF-1α is an attractive strategy for disrupting multiple pathways crucial for tumor growth. In the present study, we demonstrated that hypoxia increases the S-glutathionylation of HIF-1α and its protein levels in colon cancer cells. This effect is significantly prevented by decreasing oxidized glutathione as well as glutathione depletion, indicating that S-glutathionylation and the formation of protein-glutathione mixed disulfides is related to HIF-1α protein levels. Moreover, colon cancer cells expressing glutaredoxin 1 are resistant to inducing HIF-1α and expressing hypoxia-responsive genes under hypoxic conditions. Therefore, S-glutathionylation of HIF-1α induced by tumor hypoxia may be a novel therapeutic target for the development of new drugs.     

Proteomic Analysis Reveals Distinct Metabolic Differences Between Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF) Grown Macrophages Derived from Murine Bone Marrow Cells*

Macrophages are crucial in controlling infectious agents and tissue homeostasis. Macrophages require a wide range of functional capabilities in order to fulfill distinct roles in our body, one being rapid and robust immune responses. To gain insight into macrophage plasticity and the key regulatory protein networks governing their specific functions, we performed quantitative analyses of the proteome and phosphoproteome of murine primary GM-CSF and M-CSF grown bone marrow derived macrophages (GM-BMMs and M-BMMs, respectively) using the latest isobaric tag based tandem mass tag (TMT) labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Strikingly, metabolic processes emerged as a major difference between these macrophages. Specifically, GM-BMMs show significant enrichment of proteins involving glycolysis, the mevalonate pathway, and nitrogen compound biosynthesis. This evidence of enhanced glycolytic capability in GM-BMMs is particularly significant regarding their pro-inflammatory responses, because increased production of cytokines upon LPS stimulation in GM-BMMs depends on their acute glycolytic capacity. In contrast, M-BMMs up-regulate proteins involved in endocytosis, which correlates with a tendency toward homeostatic functions such as scavenging cellular debris. Together, our data describes a proteomic network that underlies the pro-inflammatory actions of GM-BMMs as well as the homeostatic functions of M-BMMs.Macrophages are a heterogeneous population of immune cells that are essential for the initiation and resolution of pathogen- or tissue damage-induced inflammation (1). They show remarkable plasticity that allows them to respond efficiently to environmental signals and change their phenotype and physiology upon cytokine and microbial signaling (2). These changes can give rise to populations of cells with distinct functions that are phenotypically characterized by the production of pro-inflammatory and anti-inflammatory cytokines (3). Among the growth factors that affect macrophage activation states, two cytokines that appear to be important in controlling the functions of macrophage lineage populations in inflammatory conditions are granulocyte-macrophage colony stimulating factor (GM-CSF)¹ and macrophage colony stimulating factor (M-CSF) (4). These CSFs are critical to the proper maintenance of steady-state macrophage development, although with different roles. GM-CSF has a role in inducing emergency hematopoiesis not in steady state, and influences the pathogenesis of various inflammatory as well as autoimmune diseases (5). In this line, in vitro generated GM-CSF grown macrophages are now considered as pro-inflammatory macrophages that display a robust immune responses upon LPS stimulation compared with M-CSF grown macrophages (6). In contrast, M-CSF contributes the maintenance of most resident macrophages including osteoclast in vivo and is known to affect homeostatic anti-inflammatory characteristics of macrophages. M-CSF grown macrophages are widely accepted as in vitro-generated macrophage sources because they showed relatively homogenous and stable macrophage phenotypes (7). A number of genomic studies have been performed to analyze macrophage activation in response to pro-inflammatory/anti-inflammatory stimuli. However, to date, there have been no clear reports on the global proteomic differences that govern the functional characteristics of differently differentiated or activated macrophages (8–11). To fully elucidate what enables pro-inflammatory macrophages to be poised for rapid and robust immune responses requires assessing their global intracellular proteomic network signatures.There has long been an appreciation, especially in the cancer field, for how changes in cellular activation coincide with alterations in cellular metabolic states (12, 13). Importantly, over the last couple of years it is becoming increasingly clear that immune cell activation is also coupled to profound changes in cellular metabolism and that their fate and function are metabolically regulated (14). In line with this, in this study, we found that GM-CSF grown macrophages have a higher glycolytic capacity through up-regulated glycolytic enzymes, as well as high lipid/nitrogen compound biosynthetic enzymes compared with M-CSF grown macrophages. They produce robust inflammatory cytokines upon TLR ligand stimulation only when sufficient glucose is available.Here we performed a quantitative analysis of the proteome/phosphoproteome of primary GM-CSF and M-CSF grown macrophages using the latest isobaric tag based TMT labeling and LC-MS/MS (15). This proteomic approach with high throughput technology is the first attempt to show the fundamental differences between primary GM-CSF and M-CSF grown macrophages and finally reveals that innate cellular anabolic metabolism paves the way for inducing robust immune responses. In this study, we describe individual differentially expressed proteins in the total network maps of GM-CSF and M-CSF grown macrophages and predict how they are specifically involved in initiating inflammation or resolution.