Syntaxin-1蛋白的多重功能(英文)

Syntaxin-1是特异性地分布在神经细胞突触前质膜上的蛋白。它早期被作为分子量为35 kD的synaptotagmin-1结合蛋白,但很快就被认识到是细胞质膜融合的关键蛋白。Syntaxin-1通过与SNAP25和Synaptobrevin/VAMP蛋白聚合,进而形成被认为是神经突触囊泡融合必要因子的SNARE核心复合体。作为一个多结构域的蛋白,syntaxin-1与多个突触蛋白相互作用,其作用远超出了仅作为SNARE核心复合体中一个蛋白质成员的作用。本文着重介绍了有关syntaxin-1与其它SNARE组份蛋白、munc18蛋白和钙离子通道的相互作用及其功能的最新研究进展。全面揭示syntaxin-1作为SNARE核心复合体成员的功能以及超越这一功能的作用,还有待于对其结构以及与其它突触蛋白相互作用特性的进一步深刻理解。     

Dynamics of the semantic priming shift: behavioral experiments and cortical network model

Multiple semantic priming processes between several related and/or unrelated words are at work during the processing of sequences of words. Multiple priming generates rich dynamics of effects depending on the relationship between the target word and the first and/or second prime previously presented. The experimental literature suggests that during the on-line processing of the primes, the activation can shift from associates to the first prime to associates to the second prime. Though the semantic priming shift is central to the on-line and rapid updating of word meanings in the working memory, its precise dynamics are still poorly understood and it is still a challenge to model how it functions in the cerebral cortex. Four multiple priming experiments are proposed that cross-manipulate delays and association strength between the primes and the target. Results show for the first time that association strength determines complex dynamics of the semantic priming shift, ranging from an absence of a shift to a complete shift. A cortical network model of spike frequency adaptive neuron populations is proposed to account for the non-continuous evolution of the priming shift over time. It allows linking the dynamics of the priming shift assessed at the behavioral level to the non-linear dynamics of the firing rates of neurons populations.     

Organization of lipid reserves in cotyledons of primed and aged sunflower seeds

Imbibing sunflower (Helianthus annuus L., cv. Briosol) seeds at water potentials between –2 MPa and –5 MPa leads to faster (priming) or slower (accelerated ageing) germination depending on the temperature and duration of treatment. Mobilization of food reserves may be associated with the changes in seed vigor. To study this, morphological, biochemical and phase properties of lipid, the major food reserve in sunflower, were compared in freshly harvested (i.e., control), primed and aged sunflower cotyledons using electron microscopy, biochemical analyses and differential scanning calorimetry, respectively. Lipid bodies became smaller and more dispersed throughout the cytoplasm during priming and ageing. Despite ultrastructural changes, there were few measured changes in biochemistry of the neutral lipid component; lipid content, proportion of saturated and unsaturated fatty acids and level of free fatty acids were unchanged in primed and slightly aged seeds, with only severely aged seeds showing a net decrease in polyunsaturated fatty acids and an increase in free fatty acids. Subtle changes in the calorimetric behavior of lipids within sunflower cotyledons were observed. Sunflower lipids exhibited polymorphic crystalline and amorphous solid phases when cooled to <–100°C, but priming decreased the rate of crystallization in vivo and ageing increased the rate of crystallization, but decreased percentage crystallinity. The observed changes in thermal behavior in vivo are consistent with losses and gains, respectively, of interacting non-lipid moieties in the triacylglycerol matrix.     

Memorizing environmental signals through feedback and feedforward loops

Cells in diverse organisms can store the information of previous environmental conditions for long periods of time. This form of cellular memory adjusts the cell's responses to future challenges, providing fitness advantages in fluctuating environments. Many biological functions, including cellular memory, are mediated by specific recurring patterns of interactions among proteins and genes, known as ‘network motifs.’ In this review, we focus on three well-characterized network motifs — negative feedback loops, positive feedback loops, and feedforward loops, which underlie different types of cellular memories. We describe the latest studies identifying these motifs in various molecular processes and discuss how the topologies and dynamics of these motifs can enable memory encoding and storage.     

Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration

Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.     

Priming for JA-dependent defenses using hexanoic acid is an effective mechanism to protect Arabidopsis against B. cinerea

Soil drench treatments with hexanoic acid can effectively protect Arabidopsis plants against Botrytis cinerea through a mechanism based on a stronger and faster accumulation of JA-dependent defenses.Plants impaired in ethylene, salicylic acid, abscisic acid or glutathion pathways showed intact protection by hexanoic acid upon B. cinerea infection. Accordingly, no significant changes in the SA marker gene PR-1 in either the SA or ABA hormone balance were observed in the infected and treated plants. In contrast, the JA signaling pathway showed dramatic changes after hexanoic acid treatment, mainly when the pathogen was present. The impaired JA mutants, jin1-2 and jar1, were unable to display hexanoic acid priming against the necrotroph. In addition, hexanoic acid-treated plants infected with B. cinerea showed priming in the expression of the PDF1.2, PR-4 and VSP1 genes implicated in the JA pathways. Moreover, JA and OPDA levels were primed at early stages by hexanoic acid. Treatments also stimulated increased callose accumulation in response to the pathogen. Although callose accumulation has proved an effective IR mechanism against B. cinerea, it is apparently not essential to express hexanoic acid-induced resistance (HxAc-IR) because the mutant pmr4.1 (callose synthesis defective mutant) is protected by treatment.We recently described how hexanoic acid treatments can protect tomato plants against B. cinerea by stimulating ABA-dependent callose deposition and by priming OPDA and JA-Ile production. We clearly demonstrate here that Hx-IR is a dependent plant species, since this acid protects Arabidopsis plants against the same necrotroph by priming JA-dependent defenses without enhancing callose accumulation.     

Radioresponsiveness at low doses: hyper-radiosensitivity and increased radioresistance in mammalian cells

The rationale for and importance of research on effects after radiation at "low doses" are outlined. Such basic radiobiological studies on induction of repair enzymes, protective mechanisms, priming, and hypersensitivity are certainly all relevant to treatment of cancer (see Section 1, Studies at low doses - relevance to cancer treatment). Included are examples from many groups, using various endpoints to address the possibility of an induced resistance, which has been compared to the adaptive response [M.C. Joiner, P. Lambin, E.P. Malaise, T. Robson, J.E. Arrand, K.A. Skov, B. Marples, Hypersensitivity to very low single radiation doses: its relationship to the adaptive response and induced radioresistance, Mutat. Res. 358 (1996) 171-183.]. This is not intended to be an exhaustive review--rather a re-introduction of concepts such as priming and a short survey of molecular approaches to understanding induced resistance. New data on the response of HT29 cells after treatment (priming) with co-cultured activated neutrophils are included, with protection against X-rays (S1). Analysis of previously published results in various cells lines in terms of increased radioresistance (IRR)/intrinsic sensitivity are presented which complement a study on human tumour lines [P. Lambin, E.P. Malaise, M.C. Joiner, Might intrinsic radioresistance of human tumour cells be induced by radiation?, Int. Radiat. Biol. 69 (1996) 279-290].It is not feasible to extrapolate to low doses from studies at high doses. The biological responses probably vary with dose, LET, and have variable time frames. The above approaches may lead to new types of treatment, or additional means to assess radioresponsiveness of tumours. Studies in many areas of biology would benefit from considerations of different dose regions, as the biological responses vary with dose. There may also be some implications in the fields of radiation protection and carcinogenesis, and the extensions of concepts of hyper-radiosensitivity (HRS)/IRR extended to radiation exposure are considered in Section 2, Possible relevance of IRR concepts to radiation exposure (space). More knowledge on inducible responses could open new approaches for protection and means to assess genetic predisposition. Many endpoints are used currently--clonogenic survival, mutagenesis, chromosome aberrations and more direct--proteins/genes/functions/repair/signals, as well as different biological systems. Because of scant knowledge of the relevant aspects at low doses, such as inducible/protective mechanisms, threshold, priming, dose-rate effects, LET within one system, it is still too early to draw conclusions in the area of radiation exposure. Technological advances may permit much needed studies at low doses in the areas of both treatment and protection.     

分泌囊泡启动步骤和相关调节蛋白研究进展

囊泡启动是细胞调节性分泌中非常关键的一个步骤,囊泡启动后才具备与膜融合的能力.囊泡的启动过程需要SNARE复合体的形成和许多其它蛋白如Muncl3、RIM、CAPS等的参与,但不同类型的分泌囊泡其关键的启动因子并不相同.本文主要从分泌囊泡的启动过程和不同囊泡所特异的启动因子着手,综述了囊泡转运过程中启动步骤的最新研究进展.     

Resveratrol and curcumin reduce the respiratory burst of Chlamydia-primed THP-1 cells

The intracellular bacterium Chlamydia pneumoniae is involved in the inflammation process of atherosclerosis. We previously demonstrated that C. pneumonia infected monocytes (THP-1 cells) responded to stimulation by an increased respiratory burst linked to an increased NADPH oxidase (NOX) activity. We now tested agents acting on the assembly of the NOX subunits or on protein kinase C, a trigger of NOX activity. Apocynin, resveratrol, rutin, quercetin, curcumin, and tocopherols were tested. The cells were pre-incubated with Chlamydia and the agent for 19 h, and then stimulated with phorbol myristate acetate. The NOX activity was monitored by measuring the hydrogen peroxide production. Resveratrol and curcumin (10(-4)-10(-6) M) were better inhibitors than apocynin. alpha-Tocopherol was inactive, and gamma-tocopherol inhibitor at 10(-4) M only. Quercetin was inactive, and rutin a moderate but significant inhibitor. The inhibition by resveratrol was increased by 10(-6) M rutin or quercetin. Resveratrol and curcumin thus appeared to be interesting for atherosclerosis treatment.