传粉昆虫下降背景下的授粉生态弹性: 内涵、机制和展望

全球传粉昆虫多样性正在下降, 如何保障农林生态系统传粉功能是当前研究的热点。理论上说, 传粉功能不仅与生态系统的传粉昆虫多样性相关, 还与生态系统的调节能力有关。近年来, 学者们逐渐认识到授粉生态弹性对传粉功能的影响。本文在回顾已有研究的基础之上, 总结传粉昆虫授粉生态弹性的内涵, 厘清授粉生态弹性与工程弹性、稳定性和抗性的异同。目前, 学者对授粉生态弹性形成机制开展广泛探讨, 提出功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 但这5个假说间的关系仍不清楚, 存在一词多义、词意混淆等现象。我们依次阐述功能冗余假说、密度补偿假说、响应多样性假说、连接周转假说和跨尺度弹性假说, 介绍不同假说中授粉生态弹性形成过程、研究热点和发展动态。通过解析授粉生态弹性的形成机制可知, 5个假说在内涵上存在紧密联系, 它们从不同空间尺度和研究对象下解释传粉昆虫授粉生态弹性的形成机制。未来授粉生态弹性研究将整合传粉昆虫群落动态和传粉功能动态的量化方法, 通过实验验证5个假说的合理性, 并揭示不同假说间的联系, 由此阐明授粉生态弹性的发生条件、形成阈值和动态规律。随着研究的深入, 授粉生态弹性理论有望用于指导农林生态系统传粉功能的经营管理。     

支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率等指标的影响

目的探讨支气管镜肺泡灌洗联合抗生素对小儿重症肺炎的疗效及对痰细菌清除率和其他指标的影响。方法选取我科收治的重症肺炎患儿126例,分为研究组及对照组,各63例。其中研究组在常规治疗基础上联合支气管镜肺泡灌洗及局部应用抗生素治疗,对照组采用常规治疗,比较2组患者的临床治疗效果。结果治疗后,研究组的临床有效率为90.5%,高于对照组的76.2%(χ~2=4.629,P=0.031);治疗后研究组患者的痰液中病菌清除率为77.7%,显著高于对照组的57.2%(χ~2=6.110,P=0.013);治疗后研究组患者的相关炎性指标(高敏C反应蛋白、肿瘤坏死因子α及白介素-6)均较对照组显著降低(t=3.522、4.912、4.183,P=0.033、0.032、0.033);治疗后研究组患者的相关血气指标(动脉血氧分压及氧合指数)均较对照组显著升高,而二氧化碳分压较对照组显著降低(t=3.612、3.312、6.162,P=0.039、0.040、0.028)。结论 BAL联合抗生素对小儿重症肺炎的疗效更为显著,值得临床推广应用。     

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 10⁶/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.     

Role of vimentin in cell migration

Cell migration plays a crucial role in embryonic development, wound healing, regeneration, inflammation, and immune response, as well as in dissemination of malignant tumors. Vimentin is the marker of migrating cells, but its role in cell migration is still unclear. However, recent studies have revealed novel functions for vimentin related to the migration, such as determination of cellular polarity, regulation of cell contact formation, and arrangement and transport of signal proteins involved in cell motility. The review sums up the latest data on vimentin functions and its involvement in molecular mechanisms underlying cell migration. Early studies demonstrated that vimentin expression during embryonic development is associated with cell migration. However, having obtained vimentin knockout mice without apparent impairments in development and ability to reproduce, doubts have appeared if vimentin is required for cell migration during embryonic development. In the present review, we also discuss involvement of vimentin in migration processes at different stages of development and try to resolve current contradictions concerning the role of vimentin in various events of cell migration.     

Heterologous expression of a halophilic archaeon manganese superoxide dismutase enhances salt tolerance in transgenic rice

In order to investigate new gene resource for enhancing rice tolerance to salt stress, manganese superoxide dismutase gene from halophilic archaeon (Natrinema altunense sp.) (NaMnSOD) was isolated and introduced into Oryza sativa L. cv. Nipponbare by Agrobacterium-mediated transformation. The transformants (L1 and L2) showed some NaMnSOD expression and increased total SOD and CAT activity, which contributed to higher efficiency of ROS elimination under salt stress. The levels of superoxide anion radicals (O ₂ ^·? ) and hydrogen peroxide (H₂O₂) were significantly decreased. In addition, they exhibited higher levels of photosynthesis, whereas lower relative ion leakage and MDA content compared to wild-type plants. Therefore, transgenic seedlings were phenotypically healthier, and heterologous expression of NaMnSOD could improve rice salt tolerance.     

The Arabidopsis METACASPASE9 Degradome

Metacaspases are distant relatives of the metazoan caspases, found in plants, fungi, and protists. However, in contrast with caspases, information about the physiological substrates of metacaspases is still scarce. By means of N-terminal combined fractional diagonal chromatography, the physiological substrates of METACASPASE9 (MC9; AT5G04200) were identified in young seedlings of Arabidopsis thaliana on the proteome-wide level, providing additional insight into MC9 cleavage specificity and revealing a previously unknown preference for acidic residues at the substrate prime site position P1′. The functionalities of the identified MC9 substrates hinted at metacaspase functions other than those related to cell death. These results allowed us to resolve the substrate specificity of MC9 in more detail and indicated that the activity of phosphoenolpyruvate carboxykinase 1 (AT4G37870), a key enzyme in gluconeogenesis, is enhanced upon MC9-dependent proteolysis.     

Differential responses of juvenile and adult South African abalone (Haliotis midae Linnaeus) to low and high oxygen levels

Marine invertebrates have evolved multiple responses to naturally variable environmental oxygen, all aimed at either maintaining cellular oxygen homeostasis or limiting cellular damage during or after hypoxic or hyperoxic events. We assessed organismal (rates of oxygen consumption and ammonia excretion) and cellular (heat shock protein expression, anti-oxidant enzymes) responses of juvenile and adult abalone exposed to low (~ 83% of saturation), intermediate (~ 95% of saturation) and high (~ 115% of saturation) oxygen levels for one month. Using the Comet assay, we measured DNA damage to determine whether the observed trends in the protective responses were sufficient to prevent oxidative damage to cells. Juveniles were unaffected by moderately hypoxic and hyperoxic conditions. Elevated basal rates of superoxide dismutase, glutathione peroxidase and catalase were sufficient to prevent DNA fragmentation and protein damage. Adults, with their lower basal rate of anti-oxidant enzymes, had increased DNA damage under hypoxic and hyperoxic conditions, indicating that the antioxidant enzymes were unable to prevent oxidative damage under hypoxic and hyperoxic conditions. The apparent insensitivity of juvenile abalone to decreased and increased oxygen might be related to their life history and development in algal and diatom biofilms where they are exposed to extreme diurnal fluctuations in dissolved oxygen levels.     

Enhanced Phase II Detoxification Contributes to Beneficial Effects of Dietary Restriction as Revealed by Multi-platform Metabolomics Studies

Dietary restriction (DR) has many beneficial effects, but the detailed metabolic mechanism remains largely unresolved. As diet is essentially related to metabolism, we investigated the metabolite profiles of urines from control and DR animals using NMR and LC/MS metabolomic approaches. Multivariate analysis presented distinctive metabolic profiles and marker signals from glucuronide and glycine conjugation pathways in the DR group. Broad profiling of the urine phase II metabolites with neutral loss scanning showed that levels of glucuronide and glycine conjugation metabolites were generally higher in the DR group. The up-regulation of phase II detoxification in the DR group was confirmed by mRNA and protein expression levels of uridinediphospho-glucuronosyltransferase and glycine-N-acyltransferase in actual liver tissues. Histopathology and serum biochemistry showed that DR was correlated with the beneficial effects of low levels of serum alanine transaminase and glycogen granules in liver. In addition, the Nuclear factor (erythroid-derived 2)-like 2 signaling pathway was shown to be up-regulated, providing a mechanistic clue regarding the enhanced phase II detoxification in liver tissue. Taken together, our metabolomic and biochemical studies provide a possible metabolic perspective for understanding the complex mechanism underlying the beneficial effects of DR.It has been known for more than 70 years that dietary restriction (DR)¹ can extend the life span and delay the onset of age-related diseases, based on an early rodent study showing such effects (1). However, not until the 1980s was DR recognized as a good model for studying the mechanism of or inhibitory measures for aging (2). So far, extensive studies employing model organisms such as yeasts, nematodes, fruit flies, and rodents have shown that DR has beneficial effects in most of the species studied (for a review, see Ref. 3). Most notably, a recent 20-year-long study showed that monkeys, the species closest to humans, also benefit from DR similarly (4). Although there has not been (or could not have been) a systematic study on the effects of DR on the human life span, several longitudinal studies strongly suggest that changes in dietary intake can affect the life span and/or disease-associated marker values greatly (5–7).This inverse correlation between dietary intake and long-term health strongly indicates that DR''s effects should involve metabolism, and that DR elicits the reorganization of metabolic pathways. It also seems quite natural that something we eat should affect the body''s metabolism. Despite this seemingly straightforward relationship between diet and metabolism, the mechanisms underlying the beneficial effects of DR are anything but simple. Intensive efforts, spanning decades, to understand the mechanisms of DR have identified several genes that might mediate the effects of DR, such as mTOR, IGF-1, AMPK, and SIRT1 (for a review, see Ref. 8). Still, most of them are involved in early nutrient-sensing steps, and specific metabolic pathways, especially those at the final steps actually responsible for the effects of DR, are largely unknown.This might be at least partially due to the fact that previous studies have focused mostly on genomic or proteomic changes induced by DR, instead of looking at changes in metabolism or metabolites directly. Metabolomics, which has gained much interest in recent years (9–11), might be a good alternative for addressing the mechanistic uncertainty of DR''s effects, with the direct profiling of metabolic changes elicited by environmental factors. In contrast to genomics or proteomics, which often employ DNA or proteins extracted from particular tissues, metabolomics studies mostly employ body fluids (i.e. urine or blood), which can reflect the metabolic status of multiple organs, enabling investigations at a more systemic level. In particular, urine has been used extensively to study the mechanism of external stimuli (i.e. drugs or toxic insults) at most major target organs, such as the lung, kidney, liver, or heart (12–18). Still, metabolomics studies of DR effects have been very limited. A few previous ones reported the changes in phenomenological urine metabolic markers with DR, without identification and/or validation of specific metabolic pathways reflected at the actual tissue or enzyme level (19, 20). Therefore, those studies fell short of providing a mechanistic perspective on DR''s effects. In addition, they employed either NMR or LC/MS approaches without validation across the two analytical platforms.Among the metabolic pathways that can directly affect the integrity of multiple organs, and hence long-term health, are phase II detoxification pathways (21). Typically, lipophilic endo/xenobiotics are metabolized first by a phase I system, such as cytochrome P450, which modifies the compounds so that they have hydrophilic functional groups for increased solubility. In many cases, though, these modifications might increase the reactivity of the compounds, leading to cellular damage. The phase II detoxification systems involve conjugation reactions that attach charged hydrophilic molecular moieties to reactive metabolites, thus facilitating the elimination of the harmful metabolites from body, ultimately reducing their toxicity (22). These systems are thus especially important in protecting cellular macromolecules, such as DNA and proteins, from reactive electrophilic or nucleophilic metabolites. The enzymes involved in these processes include glutathione-S-transferase (GST), sulfotransferase, glycine-N-acyltransferase (GLYAT), and uridinediphospho-glucuronosyltransferase (UGT), with the last enzyme being the most prevalent (23). The beneficial effects of phase II reactions have been particularly studied in relation to the mechanism of healthy dietary ingredients. It is well believed that many such foods can prevent cancers (hence the term “chemoprevention”) by inducing phase II detoxification systems (24–26). Although DR also substantially reduces the incidence of cancers, the exact mechanism remains elusive.Here, we employed multi-platform metabolomics to obtain metabolic perspectives on the beneficial effects of DR on rats. Our results about urine metabolomics markers suggest that DR enhances the phase II detoxification pathway, which was confirmed by means of conjugation metabolite profiling and changes in mRNA/protein expression levels of phase II enzymes in actual liver tissues. A possible molecular mechanism was also addressed through the exploration of Nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) pathway activation upon DR. We believe the current study provides new metabolic insights into DR''s beneficial effects, as well as a workflow for studying DR''s effects from a metabolic perspective.     

A Bacterial Phosphatase-Like Enzyme of the Malaria Parasite Plasmodium falciparum Possesses Tyrosine Phosphatase Activity and Is Implicated in the Regulation of Band 3 Dynamics during Parasite Invasion

Eukaryotic parasites of the genus Plasmodium cause malaria by invading and developing within host erythrocytes. Here, we demonstrate that PfShelph2, a gene product of Plasmodium falciparum that belongs to the Shewanella-like phosphatase (Shelph) subfamily, selectively hydrolyzes phosphotyrosine, as shown for other previously studied Shelph family members. In the extracellular merozoite stage, PfShelph2 localizes to vesicles that appear to be distinct from those of rhoptry, dense granule, or microneme organelles. During invasion, PfShelph2 is released from these vesicles and exported to the host erythrocyte. In vitro, PfShelph2 shows tyrosine phosphatase activity against the host erythrocyte protein Band 3, which is the most abundant tyrosine-phosphorylated species of the erythrocyte. During P. falciparum invasion, Band 3 undergoes dynamic and rapid clearance from the invasion junction within 1 to 2 s of parasite attachment to the erythrocyte. Release of Pfshelph2 occurs after clearance of Band 3 from the parasite-host cell interface and when the parasite is nearly or completely enclosed in the nascent vacuole. We propose a model in which the phosphatase modifies Band 3 in time to restore its interaction with the cytoskeleton and thus reestablishes the erythrocyte cytoskeletal network at the end of the invasion process.