生物和非生物逆境胁迫下的植物系统信号

复杂多变的自然环境使植物进化出许多适应策略, 其中由局部胁迫引起的系统响应广泛存在, 精细调节植物的生长发育和环境适应能力。植物系统响应的诱导因素首先引起植物从局部到全株范围的信号转导, 这类信号称为系统信号。当受到外界刺激时, 植物首先在受刺激细胞内触发化学信号分子的变化, 如茉莉酸和水杨酸甲酯等在浓度和信号强度方面发生变化; 进而, 伴随着一系列复杂的信号转换, 多种信号组分共同完成系统响应的激活。植物激素、小分子肽和RNA等被认为是缓慢系统信号通路中的关键组分, 而目前也有大量研究阐释了由活性氧、钙信号和电信号相互偶联组成的快速系统信号通路。植物系统信号对其生存和繁衍至关重要, 其精确的转导机制仍值得深入研究。该文综述了植物响应环境的系统信号转导研究进展, 对关键的系统信号组分及其转导机制进行了总结, 同时对植物系统信号传递的研究方向进行了展望。     

Systemic Non-Reproductive Effects of Sex Steroids in Adult Males and Females

Sex steroids are well known for their reproductive actions, however, their roles are not confined to reproduction only and they have been shown to exert wide ranging effects on systemic physiology. Further, the effects of the so-called male and female sex steroids are not limited to their respective genders but they are present in both sexes where they have a significant impact upon systemic functions, reproductive as well as non-reproductive. This work reviews the existing knowledge base and recent reports on the effects of sex steroids on non-reproductive physiology.     

Synthesis and pharmacological evaluation of conjugates of prednisolone and non-steroidal anti-inflammatory agents

Esters of prednisolone with ibuprofen and indomethacin were prepared by coupling the 21-hydroxy moiety of the glucocorticoid to the carboxylic group of the non-steroidal anti-inflammatory agents. The local and systemic anti-inflammatory activities of the conjugates were evaluated using the cotton pellet granuloma bioassay and their topical activity evaluated by the croton oil-induced ear edema assay, in male Sprague-Dawley rats. The results indicate that these conjugates possess greater local and topical anti-inflammatory activity than prednisolone. In the subacute ear edema bioassay, the conjugates displayed no discernible untoward systemic effects, unlike prednisolone and prednisolone acetate, which elicited significant adverse systemic effects, at equipotent doses. These findings suggest that the chemical coupling of prednisolone and non-steroidal anti-inflammatory agents produced compounds with enhanced anti-inflammatory potencies and reduced systemic toxicities, particularly when administered topically.     

Deletion of FADD in Macrophages and Granulocytes Results in RIP3- and MyD88-Dependent Systemic Inflammation

Myeloid cells, which include monocytes, macrophages, and granulocytes, are important innate immune cells, but the mechanism and downstream effect of their cell death on the immune system is not completely clear. Necroptosis is an alternate form of cell death that can be triggered when death receptor-mediated apoptosis is blocked, for example, in stimulated Fas-associated Death Domain (FADD) deficient cells. We report here that mice deficient for FADD in myeloid cells (mFADD^-/-) exhibit systemic inflammation with elevated inflammatory cytokines and increased levels of myeloid and B cell populations while their dendritic and T cell numbers are normal. These phenotypes were abolished when RIP3 deficiency was introduced, suggesting that systemic inflammation is caused by RIP3-dependent necroptotic and/or inflammatory activity. We further found that loss of MyD88 can rescue the systemic inflammation observed in these mice. These phenotypes are surprisingly similar to that of dendritic cell (DC)-specific FADD deficient mice with the exception that DC numbers are normal in mFADD^-/- mice. Together these data support the notion that innate immune cells are constantly being stimulated through the MyD88-dependent pathway and aberrations in their cell death machinery can result in systemic effects on the immune system.     

Regulation of Shoot and Root Development through Mutual Signaling

Plants adjust their development in relation to the availability of nutrient sources. This necessitates signaling between root and shoot. Aside from the well-known systemic signaling processes mediated by auxin, cytokinin, and sugars, new pathways involving carotenoid-derived hormones have recently been identified. The auxin-responsive MAX pathway controls shoot branching through the biosynthesis of strigolactone in the roots. The BYPASS1 gene affects the production of an as-yet unknown carotenoid-derived substance in roots that promotes shoot development. Novel local and systemic mechanisms that control adaptive root development in response to nitrogen and phosphorus starvation were recently discovered. Notably, the ability of the NITRATE TRANSPORTER 1.1 to transport auxin drew for the first time a functional link between auxin, root development, and nitrate availability in soil. The study of plant response to phosphorus starvation allowed the identification of a systemic mobile miRNA. Deciphering and integrating these signaling pathways at the whole-plant level provide a new perspective for understanding how plants regulate their development in response to environmental cues.     

The gene encoding interleukin-13: a susceptibility locus for asthma and related traits

Respirable antisense oligonucleotides (RASONs), which attenuate specific disease-associated mRNAs, represent a new class of respiratory therapeutics with considerable potential. RASONs overcome previous obstacles that have impeded the development of antisense therapeutics targeting diseases in other organ systems. RASONs are delivered directly to the target tissue via inhalation; their uptake seems to be enhanced by cationic properties inherent in pulmonary surfactant, and, because of the markedly different target properties of mRNA and proteins, they can have very long durations of effect compared with traditional drugs targeting the protein of the same gene. RASONs contain chemical modifications that decrease their degradation by cellular nucleases. However, total insensitivity to nucleases is probably not an optimal design criterion for RASONs, because moderate nuclease sensitivity can prevent their systemic delivery, decreasing the potential for systemic toxicity. EPI-2010 is a 21-mer phosphorothioate RASON that attenuates bronchoconstriction, inflammation and surfactant depletion in preclinical models of human asthma, has a duration of effect of seven days, and seems to undergo minimal systemic delivery.     

Gene expression profiling in circulating endothelial cells from systemic sclerosis patients shows an altered control of apoptosis and angiogenesis that is modified by iloprost infusion

Introduction  

Circulating endothelial cells are increased in patients affected by systemic sclerosis (SSc) and their number strongly correlates with vascular damage. The effects of iloprost in systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of iloprost infusion and gene expression in patients with systemic sclerosis.     

APOE genotype and an ApoE-mimetic peptide modify the systemic and central nervous system inflammatory response

Human apolipoprotein E is the major apolipoprotein expressed in the brain and exists as three isoforms, designated E2, E3, and E4. Although evidence suggests that apolipoprotein E plays an important role in modifying systemic and brain inflammatory responses, there is little data investigating apoE isoform-specific effects in vivo. In this study, we compared the inflammatory responses of targeted-replacement mice expressing the human APOE3 and APOE4 genes after intravenous administration of lipopolysaccharide. Animals expressing the E4 allele had significantly greater systemic and brain elevations of the pro-inflammatory cytokines TNFalpha and IL-6 as compared with their APOE3 counterparts, suggesting an isoform-specific effect of the immunomodulatory properties of apoE. Furthermore, intravenous administration of a small apoE-mimetic peptide derived from the receptor-binding region of the apoE holoprotein (apoE-(133-149)) similarly suppressed both systemic and brain inflammatory responses in mice after lipopolysaccharide administration. These results suggest that apoE plays an isoform-specific role in mediating the systemic and brain inflammatory responses. Moreover, because exogenous administration of this apoE mimetic peptide is effective at suppressing both systemic and brain inflammation, it may represent a novel therapeutic strategy for diseases characterized by systemic or central nervous system inflammation, such as septic shock, multiple sclerosis, and traumatic brain injury.     

Isotypic characteristics of serum and secretory O antibodies and local immunological memory in the parenteral immunization of guinea pigs with a ribosomal Shigella vaccine

Guinea pigs were immunized subcutaneously with ribosomal vaccine prepared from S. sonnei and their systemic and local humoral response was studied by means of ELISA techniques with the use of monospecific antisera to guinea pig IgA and IgG. Injection of the ribosomal vaccine leads to a significant rise in the levels of IgA O-antibodies in tears, IgG and IgA O-antibodies in the serum. The presence of IgA O-antibodies in tears was seemingly the result of their local synthesis rather than the seepage of serum IgA. The stimulation of the local and systemic anti-O response was more pronounced after parenteral immunization with the ribosomal vaccine than after immunization with the corresponding dose of lipopolysaccharide (LPS). Parenteral immunization with the ribosomal vaccine induced the development of both systemic and local memory. The priming effect produced by relatively small doses of this vaccine (40 micrograms), administered parenterally, was similar to the effect of prolonged and intensive stimulation ensured by 10-day feeding with LPS (the total dose being 5,000 micrograms).     

Separation of fNIRS Signals into Functional and Systemic Components Based on Differences in Hemodynamic Modalities

In conventional functional near-infrared spectroscopy (fNIRS), systemic physiological fluctuations evoked by a body''s motion and psychophysiological changes often contaminate fNIRS signals. We propose a novel method for separating functional and systemic signals based on their hemodynamic differences. Considering their physiological origins, we assumed a negative and positive linear relationship between oxy- and deoxyhemoglobin changes of functional and systemic signals, respectively. Their coefficients are determined by an empirical procedure. The proposed method was compared to conventional and multi-distance NIRS. The results were as follows: (1) Nonfunctional tasks evoked substantial oxyhemoglobin changes, and comparatively smaller deoxyhemoglobin changes, in the same direction by conventional NIRS. The systemic components estimated by the proposed method were similar to the above finding. The estimated functional components were very small. (2) During finger-tapping tasks, laterality in the functional component was more distinctive using our proposed method than that by conventional fNIRS. The systemic component indicated task-evoked changes, regardless of the finger used to perform the task. (3) For all tasks, the functional components were highly coincident with signals estimated by multi-distance NIRS. These results strongly suggest that the functional component obtained by the proposed method originates in the cerebral cortical layer. We believe that the proposed method could improve the reliability of fNIRS measurements without any modification in commercially available instruments.     

Analysis of responses to endothelins in the rabbit pulmonary and systemic vascular beds

The effects of two isoforms of human endothelin (ET) on the pulmonary and systemic vascular beds were compared in the anesthetized intact-chest rabbit under conditions of constant pulmonary blood flow and left atrial pressure. Intralobar bolus injections of ET-1 (0.1-1 micrograms) and ET-3 (1-3 micrograms) produced modest vasoconstriction in the pulmonary vascular bed, whereas both peptides decreased systemic arterial pressure. The pulmonary vasoconstrictor response to ET-1 and ET-3 was inhibited by intralobar infusion of nitrendipine but was not altered by indomethacin. In contrast to the small effects of ET-1 and ET-3 on intact pulmonary resistance vessels, both peptides markedly contracted isolated pulmonary conductance vessels, with greater activity on venous than on arterial segments. Intravenous bolus injection of ET-1 (0.1-0.3 micrograms) or ET-3 (0.3-1 microgram) decreased systemic arterial pressure, increased cardiac output, and markedly decreased systemic vascular resistance. Higher doses of ET-1 produce a biphasic systemic vascular response with a prominent secondary pressor component. The present data suggest that the pulmonary vasoconstrictor activity of ET-1 is greater than that of ET-3 and their pressor activity depends on an extracellular source of calcium. The pulmonary and systemic hemodynamic effects of ET-1 and ET-3 in the rabbit do not depend on cyclooxygenase products. The systemic vasodilator response to ET-1 is not altered by first-pass lung transit. Furthermore the systemic vasodilator response to both peptides occurs independent of activation of muscarinic, beta 2-adrenergic, and platelet-activating factor receptors. Although ET-1 and ET-3 were initially reported as vasoconstrictor peptides, the present data suggest that, by having unique and potent systemic vasodilator activity, ET-1 and ET-3 act differently in the systemic and pulmonary vascular beds under resting conditions in the rabbit.     

The FMRFamide Neuropeptide FLP-20 Acts as a Systemic Signal for Starvation Responses in Caenorhabditis elegans

Most animals face frequent periods of starvation throughout their entire life and thus need to appropriately adjust their behavior and metabolism during starvation for their survival. Such adaptive responses are regulated by a complex set of systemic signals, including hormones and neuropeptides. While much progress has been made in identifying pathways that regulate nutrient-excessive states, it is still incompletely understood how animals systemically signal their nutrient-deficient states. Here, we showed that the FMRFamide neuropeptide FLP-20 modulates a systemic starvation response in Caenorhabditis elegans. We found that mutation of flp-20 rescued the starvation hypersensitivity of the G protein β-subunit gpb-2 mutants by suppressing excessive autophagy. FLP-20 acted in AIB neurons, where the metabotropic glutamate receptor MGL-2 also functions to modulate a systemic starvation response. Furthermore, FLP-20 modulated starvation-induced fat degradation in a manner dependent on the receptor-type guanylate cyclase GCY-28. Collectively, our results reveal a circuit that senses and signals nutrient-deficient states to modulate a systemic starvation response in multicellular organisms.     

Identification and typing of Malassezia yeasts using amplified fragment length polymorphism (AFLP), random amplified polymorphic DNA (RAPD) and denaturing gradient gel electrophoresis (DGGE)

Three molecular tools, amplified fragment length polymorphism (AFLP), denaturing gradient gel electrophoresis (DGGE) and random amplified polymorphic DNA (RAPD) analysis, were explored for their usefulness to identify isolates of Malassezia yeasts. All seven species could be separated by AFLP and DGGE. Using AFLP, four genotypes could be distinguished within M. furfur. AFLP genotype 4 contained only isolates from deep human sources, and ca. 80% of these isolates were from patients with systemic disease. Most of the systemic isolates belonged to a single RAPD genotype. This suggests that systemic conditions strongly select for a particular genotype. Although the clinical use of DGGE may be limited due to technical demands, it remains a powerful tool for the analysis of complex clinical samples.     

The tumor macroenvironment and systemic regulation of breast cancer progression

Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.     

Plant age, communication, and resistance to herbivores: young sagebrush plants are better emitters and receivers

Plants progress through a series of distinct stages during development, although the role of plant ontogeny in their defenses against herbivores is poorly understood. Recent work indicates that many plants activate systemic induced resistance after herbivore attack, although the relationship between resistance and ontogeny has not been a focus of this work. In addition, for sagebrush and a few other species, individuals near neighbors that experience simulated herbivory become more resistant to subsequent attack. Volatile, airborne cues are required for both systemic induced resistance among branches and for communication among individuals. We conducted experiments in stands of sagebrush of mixed ages to determine effects of plant age on volatile signaling between branches and individuals. Young and old control plants did not differ in levels of chewing damage that they experienced. Systemic induced resistance among branches was only observed for young plants. Young plants showed strong evidence of systemic resistance only if airflow was permitted among branches; plants with only vascular connections showed no systemic resistance. We also found evidence for volatile communication between individuals. For airborne communication, young plants were more effective emitters of cues as well as more responsive receivers of volatile cues.     

Mesenchymal stem cells: biological characteristics and potential clinical applications

Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal-like cells. Several methods are currently available for isolation of the MSC based on their physical and physico-chemical characteristics, for example, adherence to plastics or other extracellular matrix components. Because of the ease of their isolation and their extensive differentiation potential, MSC are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.     

Shining light on lupus and UV

People exposed to sunlight can develop erythema, DNA damage, and photoimmunosupression. Extended exposure of normal epidermis to sunlight will induce dysmorphic keratinocytes with pyknotic nuclei scattered throughout the spinous layer. These 'sunburn cells' are apoptotic keratinocytes and are usually cleared within 48 hours after sunburn. Patients with lupus erythematosus, however, whether it be the discoid, subacute cutaneous, systemic, or tumid form, develop new cutaneous lesions and can experience systemic worsening of their disease. Are sunlight-induced keratinocyte apoptosis and the immune response to these cells abnormal in lupus patients?     

Oxygen free radicals and the systemic inflammatory response

The generation of oxygen free radicals is known to be involved in the development of the systemic inflammatory response syndrome. In addition to their actions as noxious mediators generated by inflammatory cells, these molecules play also a crucial role contributing to the onset and progression of inflammation in distant organs. In the early stages of the process, free radicals exert their actions via activation of nuclear factors, as NFkappaB or AP-1, that induce the synthesis of cytokines. In later stages, endothelial cells are activated due to the synergy between free radicals and cytokines, promoting the synthesis of inflammatory mediators and adhesion molecules. Finally, free radicals exert their toxic effects at the site of inflammation by reacting with different cell components, inducing loss of function and cell death. This review focuses on progress in the understanding the different actions of free radicals at the sequential stages of the development of the systemic inflammatory response.     

Investigations on fungicides

A series of pyrazole derivatives, which are structural analogues of the systemic fungicide, carboxin (5,6-dihydro-2-methyl-i,4-oxathiin-3-carboxani-lide), have been synthesized and their antifungal properties investigated. 3,5-dimethylpyrazole-i-carboxanilides, although active in vitro and in leaf disk tests, showed no systemic antifungal activity. Certain 3,5-dimethylpyra-zole-4-carboxanilides, however, and their corresponding 1 -methyl derivatives, showed good activity in spore germination tests and high activity against wheat and broad bean rusts in vivo. In several instances, systemic antifungal activity was of the same order as that of carboxin, although generally accompanied by higher levels of phytotoxicity. 1 -Phenyl derivatives were essentially inactive. Substitution in the anilide ring by 3-methyl, 2-methyl or 3-chloro groups resulted in enhanced systemic activity, while 4-chloro, 4-ethoxy, 2-nitro and 3,4-dichloro substituents reduced activity.     

Form and Function in Reptilian Circulations

Consistent with the great variation in their circulatory morphology,there are distinct variations in the cardiovascular physiologyof extant reptiles. The chelonian and squamate reptiles havea complexly structured heart that includes three partially separatedventricular cava. In most species (under most conditions), theventricle acts as a single pressure pump perfusing both thepulmonary and systemic circuits. However, the varanid lizardsprovide a striking exception. Subtle evolutionary changes incardiac morphology allow the ventricle of the varanid lizardto divide functionally during systole into a low pressure, pulmonarypump and a high pressure, systemic pump. The crocodilians representyet another anatomical and physiological pattern. The ventricleis completely divided into left and right chambers as in homeotherms,but the systemic and pulmonary circuits may still communicatethrough the left aorta that arises from the right ventricle. A fundamental feature of all reptilian circulations is the abilityto regulate the distribution of cardiac output between systemicand pulmonary circuits via central vascular blood shunts.Regardlessof species, mechanisms for regulating intracardiac shuntinginvolve changes in the balance between peripheral resistanceof the pulmonary and systemic circulations, and adjustmentsin cardiac performance per se. Several hypotheses are presentedthat suggest selective advantages for central vascular shuntingin intermittent breathing reptiles with variable body temperatureand metabolic rate.