Dyskeratosis congenita as a disorder of telomere maintenance

Since 1998, there have been great advances in our understanding of the pathogenesis of dyskeratosis congenita (DC), a rare inherited bone marrow failure and cancer predisposition syndrome with prominent mucocutaneous abnormalities and features of premature aging. DC is now characterized molecularly by the presence of short age-adjusted telomeres. Mutations in seven genes have been unequivocally associated with DC, each with a role in telomere length maintenance. These observations, combined with knowledge that progressive telomere shortening can impose a proliferative barrier on dividing cells and contribute to chromosome instability, have led to the understanding that extreme telomere shortening drives the clinical features of DC. However, some of the genes implicated in DC encode proteins that are also components of H/ACA-ribonucleoprotein enzymes, which are responsible for the post-translational modification of ribosomal and spliceosomal RNAs, raising the question whether alterations in these activities play a role in the pathogenesis of DC. In addition, recent reports suggest that some cases of DC may not be characterized by short age-adjusted telomeres. This review will highlight our current knowledge of the telomere length defects in DC and the factors involved in its development.     

Mouse and human dendritic cell subtypes

Dendritic cells (DCs) collect and process antigens for presentation to T cells, but there are many variations on this basic theme. DCs differ in the regulatory signals they transmit, directing T cells to different types of immune response or to tolerance. Although many DC subtypes arise from separate developmental pathways, their development and function are modulated by exogenous factors. Therefore, we must study the dynamics of the DC network in response to microbial invasion. Despite the difficulty of comparing the DC systems of humans and mice, recent work has revealed much common ground.     

DC6, a novel type of Dictyostelium discoideum gene regulated by secreted factors but not by cAMP

We have isolated a gene, DC6, which is induced in the early aggregative stages of development in Dictyostelium discoideum. The increase in DC6 expression is dependent on high cell density, indicating that cellular interactions are required for DC6 induction. In low-cell-density cultures, the induction of DC6 occurs if supplied with conditioned medium of developing cells, suggesting that secreted factors are involved in DC6 induction. The expression of DC6 is not affected (1) in the presence of caffeine or adenosine, which block the production or the action of cAMP pulses, (2) in the presence of high concentrations of cAMP, or (3) in mutant strains (Synag7 and FrigidA), which are defective in transduction pathways of cAMP pulse signals. These results indicate that the induction of DC6 does not require extracellular cAMP pulse signals, which are known to regulate the expression of many genes in the early development. Independence of cAMP signals and dependence on other unknown cellular interactions are prominent characteristics of DC6.     

Dendritic cell differentiation from hematopoietic CD34+ progenitor cells

Dendritic cells (DC) are the most powerful antigen presenting cells (APC) and play a pivotal role in initiating the immune response. In light of their unique properties, DC have been proposed as a tool to enhance immunity against infectious agents and in anticancer vaccine strategies. In the last few years, the development of DC has been extensively investigated. The present paper summarizes the most recent findings on the differentiation of myeloid DC from hematopoietic CD34+ progenitors and methods for DC generation in vitro. A better understanding of DC function has important implications for their use in clinical settings.     

Integration of pro- and anti-angiogenic signals by endothelial cells

Angiogenesis or neovascularization is a complex multi-step physiological process that occurs throughout life both in normal tissues and in disease. It is tightly regulated by the balance between pro-angiogenic and anti-angiogenic factors. The angiogenic switch has been identified as the key step during tumor progression in which the balance between pro-angiogenic and anti-angiogenic factors leans toward pro-angiogenic stimuli promoting the progression of tumors from dormancy to dysplasia and ultimately malignancy. This event can be described as either the outcome of a genetic event occurring in cancer cells themselves, or the positive and negative cross-talk between tumor-associated endothelial cells and other cellular components of the tumor microenvironment. In recent years, the mechanisms underlying the angiogenic switch have been extensively investigated in particular to identify therapeutic targets that can lead to development of effective therapies. In this review, we will discuss the current findings on the regulatory pathways in endothelial cells that are involved in the angiogenic switch with an emphasis on the role of anti-angiogenic protein, thrombospondin-1 (TSP-1) and pro-angiogenic factor, vascular endothelial growth factor (VEGF).     

Cell cycle regulation in the developing lens

Regulation of cell proliferation is a critical aspect of the development of multicellular organisms. The ocular lens is an excellent model system in which to unravel the mechanisms controlling cell proliferation during development. In recent years, several cell cycle regulators have been shown to be essential for maintaining normal patterns of lens cell proliferation. Additionally, many growth factor signaling pathways and cell adhesion factors have been shown to have the capacity to regulate lens cell proliferation. Given this complexity, understanding the cross talk between these many signaling pathways and how they are coordinated are important directions for the future.     

Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections

Influenza is still one of the major plagues worldwide with the threatening potential to cause pandemics. In recent years, increasing levels of resistance to the four FDA approved anti-influenza virus drugs have been described. This situation underlines the urgent need for novel anti-virals in preparation for future influenza epidemics or pandemics. Although the anti-virals currently in use target viral factors such as the neuraminidase or the M2 ion channel, there is an increase in pre-clinical approaches that focus on cellular factors or pathways that directly or indirectly interact with virus replication. This does not only include inhibitors of virus-supportive signaling cascades but also interaction blockers of viral proteins with host cell proteins. This review aims to highlight some of these novel approaches that represent a paradigm change in anti-viral strategies against the influenza virus. Although most of these approaches are still in an early phase of preclinical development they might be very promising particularly with respect to the prevention of viral resistance to potential drugs.     

The role of dendritic cell subsets in selection between tolerance and immunity

Dendritic cells (DC) are considered nature's adjuvants. They are potent stimulators of naive T cells and key inducers of primary immune responses. In recent times it has become clear that they can also play a central role in the development of T cell tolerance. Further complicating our understanding of DC function is the realization that DC can no longer be viewed as a homogeneous cell type. Rather, they exist as a complex mixture of strikingly different cell populations. The mechanisms that drive the conflicting immunological outcomes of tolerance and immunity have been the subject of intense scrutiny in recent years, most recently in terms of how the various DC subsets are involved in these events. Here we review recent experiments that provide insights into how DC subsets control the outcome of T cell activation and in so doing select between immunity and tolerance induction.     

Pax基因家族在果蝇发育过程中的调控作用

Pax是一个在进化上相当保守的基因家族, 它们编码的产物是一组极为重要的转录调控因子, 并存在于从果蝇到人类的各种生物体中, 参与细胞内信号传导通路的调控, 在胚胎发育过程中对细胞分化、更新、凋亡起重要的调控作用, 影响器官和组织的形成。果蝇中已发现10个Pax基因家族成员, 它们对果蝇胚胎发育及成虫组织器官的分化有非常重要的调控作用。文章结合最新的研究进展, 就果蝇中Pax基因的结构、表达模式和主要功能做一简要综述。     

Dendritic cell dysfunction in cancer: a mechanism for immunosuppression

Several reports have demonstrated that tumours are not intrinsically resistant to the immune response. However, neoplasias commonly fail to initiate and maintain adequate immunity. A number of factors have been implicated in causing the failure, including aberrant antigen processing by tumour cells, anergy or deletion of T cells, and recruitment of inhibitory/regulatory cell types. It has been suggested that dysfunction of dendritic cells (DC) induced by the tumour is one of the critical mechanisms to escape immune surveillance. As a minor subset of leucocytes, DC are the key APC for initiating immune responses. DC are poised at the boundaries of the periphery and the inner tissues, sampling antigens of diverse origin. Following their encounter with antigen or danger signals, DC migrate to lymph nodes, where they activate effector cells essential for tumour clearance. Although the DC system is highly heterogeneous, the differentiation and function of DC populations is largely regulated by exogenous factors. Malignancies appear to exploit this by producing a plethora of immunosuppressive factors capable of affecting DC, thus exerting systemic effects on immune function. This review examines recent findings on the effects of tumour-derived factors inducing DC dysfunction and in particular examines the findings on alteration of DC differentiation, maturation and longevity as a potent mechanism for immune suppression in cancer.     

MYB类转录因子对花药和花粉发育的调控途径

花药发育和花粉形成的各个步骤由众多基因控制,一些转录因子通过调控花药发育相关基因的表达,是功能性花粉形成的关键因子。MYB类转录因子作为植物中最大的转录因子家族,是其中非常重要的一类转录因子。该文结合近年来国内外有关被子植物花粉发育相关MYB转录因子在花药发育和花粉形成的调控途径,包括绒毡层发育、胼胝质的沉积和降解、光合产物的运输、花药的开裂以及雄配子体形成过程中所起的重要作用等方面的研究进展,重点对MYB类转录因子通过形成对绒毡层发育、同化物分配、苯丙烷物质代谢等相关靶位基因的控制网络,转录调控植物花粉发育和花药开裂过程等研究进行综述讨论。     

Controlling of bone morphogenetic protein signaling

Bone morphogenetic proteins (BMPs) are multifunctional growth factors and play crucial roles during embryonic development, skeletal development, and cell fate determination. Their signals are transduced from cell membrane to the nucleus through intracellular signaling mediators. At present, different signaling pathways have been identified, and elaborate of network of regulators involved in the signaling control. The aim of the present review is to describe the recent understanding of BMPs signaling with emphasis on the regulation of its signal transduction at extracellular level, intracellular level, Smad-interacting factors in the nucleus, and Smad-independent signaling pathways, respectively.     

高等植物叶绿素生物合成的联乙烯还原酶及编码基因研究进展

联乙烯还原酶(DVR)将各种叶绿素中间物质的8-乙烯基转化为乙基,是叶绿素生物合成必不可少的一个关键酶。迄今已在高等植物中检测到5种DVR活性。水稻和玉米的重组DVR蛋白能将联乙烯叶绿素a、叶绿素酸酯a、原叶绿素酸酯a、镁原卟啉Ⅸ单甲酯和镁原卟啉Ⅸ分别转化为相应的单乙烯物质,从而证实了这5种DVR活性。在高等植物中各种DVR活性是由一个基因编码的具有广谱底物专化性的DVR蛋白所催化,但来源于不同物种的DVR蛋白的催化活性可能具有极显著的差异,并且即使是同一个DVR蛋白,对不同的联乙烯底物也可能具有显著不同的催化活性。在此基础上,提出了"源于一个联乙烯还原酶的叶绿素生物合成多分支路径"假说。该文对近年来国内外有关高等植物叶绿素生物合成途径中联乙烯中间物质与联乙烯还原酶活性、联乙烯还原酶基因的克隆及重组酶活性检测、联乙烯还原酶的数目与叶绿素生物合成的多分支路径等方面的研究进展进行综述,并讨论了有待进一步探讨的若干问题。     

Nuclear receptor signalling in dendritic cells connects lipids, the genome and immune function

Dendritic cells (DCs) are sentinels of the immune system and represent a heterogeneous cell population. The existence of distinct DC subsets is due to their inherent plasticity and to the changing microenvironment modulating their immunological properties. Numerous signalling pathways have impacts on DCs. It appears that besides cytokines/chemokines, lipid mediators also have profound effects on the immunogenicity of DCs. Some of these lipid mediators exert an effect through nuclear hormone receptors. Interestingly, more recent findings suggest that DCs are able to convert precursors to active hormones, ligands for nuclear receptors. Some of these DC-derived lipids, in particular retinoic acid (RA), have a central function in shaping T-cell development and effector functions. In this review, we summarize and highlight the function of a set of nuclear receptors (PPARgamma, RA receptor, vitamin D receptor and glucocorticoid receptor) in DC biology. Defining the contribution of nuclear hormone receptor signalling in DCs can help one to understand the regulatory logic of lipid signalling and allow the exploitation of their potential for therapeutic intervention in various immunological diseases.     

Molecular interactions between light and hormone signaling to control plant growth

As sessile organisms, plants modulate their growth rate and development according to the continuous variation in the conditions of their surrounding environment, an ability referred to as plasticity. This ability relies on a web of interactions between signaling pathways triggered by endogenous and environmental cues. How changes in environmental factors are interpreted by the plant in terms of developmental or growth cues or, in other words, how they contribute to plant plasticity is a current, major question in plant biology. Light stands out among the environmental factors that shape plant development. Plants have evolved systems that allow them to monitor both quantitative and qualitative differences in the light that they perceive, that render important changes in their growth habit. In this review we focus on recent findings about how information from this environmental cue is integrated during de-etiolation and in the shade-avoidance syndrome, and modulated by several hormone pathways—the endogenous cues. In some cases the interaction between a hormone and the light signaling pathways is reciprocal, as is the case of the gibberellin pathway, whereas in other cases hormone pathways act downstream of the environmental cue to regulate growth. Moreover, the circadian clock adds an additional layer of regulation, which has been proposed to integrate the information provided by light with that provided by hormone pathways, to regulate daily growth.