Herpesvirus saimiri encodes homologues of G protein-coupled receptors and cyclins.

Herpesvirus saimiri (HVS) is a T-lymphotropic gammaherpesvirus which establishes asymptomatic infections in its natural host the squirrel monkey (Saimiri sciureus), but which causes fatal lymphoproliferative diseases in other New World primates. Sequencing studies show HVS is closely related to the human B-lymphotropic gammaherpesvirus Epstein-Barr virus (EBV). However, despite the general colinearity between the genomes of HVS and EBV, HVS contains genes not found in EBV or in the genomes of any of the other sequenced herpesviruses. We have identified two genes, occurring in a region of divergence between HVS and EBV, that have cellular homologues. One of these, ECRF3, is homologous to the genes encoding the human cytomegalovirus (HCMV) and cellular G protein-coupled receptor family of proteins. The other HVS gene, ECLF2, is homologous to the genes encoding cellular cyclins and to our knowledge is the first reported example of a viral cyclin. The presence of G protein-coupled receptor and cyclin homologues in HVS suggests that these genes may be important in the regulation of viral and cellular processes during productive and/or latent infection of host cells, and in particular may be of relevance in the transformation and rapid proliferation of T cells during HVS infections of hosts susceptible to HVS-induced lymphoproliferative diseases.     

Positive feedback sharpens the anaphase switch

At the onset of anaphase, sister-chromatid cohesion is dissolved abruptly and irreversibly, ensuring that all chromosome pairs disjoin almost simultaneously. The regulatory mechanisms that generate this switch-like behaviour are unclear. Anaphase is initiated when a ubiquitin ligase, the anaphase-promoting complex (APC), triggers the destruction of securin, thereby allowing separase, a protease, to disrupt sister-chromatid cohesion. Here we demonstrate that the cyclin-dependent kinase 1 (Cdk1)-dependent phosphorylation of securin near its destruction-box motif inhibits securin ubiquitination by the APC. The phosphatase Cdc14 reverses securin phosphorylation, thereby increasing the rate of securin ubiquitination. Because separase is known to activate Cdc14 (refs 5 and 6), our results support the existence of a positive feedback loop that increases the abruptness of anaphase. Consistent with this model, we show that mutations that disrupt securin phosphoregulation decrease the synchrony of chromosome segregation. Our results also suggest that coupling securin degradation with changes in Cdk1 and Cdc14 activities helps coordinate the initiation of sister-chromatid separation with changes in spindle dynamics.     

Induced intragenic recombination in yeast can occur during the G1 mitotic phase.

The conditional cell division cycle yeast mutants cdc have been used to demonstrate that intragenic recombination induced by ultraviolet or gamma rays occurs in diploids arrested in G1, a short time after irradiation and before the initiation of the S phase. This implies that pairing of homologous chromosomes does not require duplicated chromatids.     

Evidence that a free-running oscillator drives G1 events in the budding yeast cell cycle.

In yeast and somatic cells, mechanisms ensure cell-cycle events are initiated only when preceding events have been completed. In contrast, interruption of specific cell-cycle processes in early embryonic cells of many organisms does not affect the timing of subsequent events, indicating that cell-cycle events are triggered by a free-running cell-cycle oscillator. Here we present evidence for an independent cell-cycle oscillator in the budding yeast Saccharomyces cerevisiae. We observed periodic activation of events normally restricted to the G1 phase of the cell cycle, in cells lacking mitotic cyclin-dependent kinase activities that are essential for cell-cycle progression. As in embryonic cells, G1 events cycled on schedule, in the absence of S phase or mitosis, with a period similar to the cell-cycle time of wild-type cells. Oscillations of similar periodicity were observed in cells responding to mating pheromone in the absence of G1 cyclin (Cln)- and mitotic cyclin (Clb)-associated kinase activity, indicating that the oscillator may function independently of cyclin-dependent kinase dynamics. We also show that Clb-associated kinase activity is essential for ensuring dependencies by preventing the initiation of new G1 events when cell-cycle progression is delayed.     

Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor stimulation.

Glutamate is important in several forms of synaptic plasticity such as long-term potentiation, and in neuronal cell degeneration. Glutamate activates several types of receptors, including a metabotropic receptor that is sensitive to trans-1-amino-cyclopenthyl-1,3-dicarboxylate, coupled to G protein(s) and linked to inositol phospholipid metabolism. The activation of the metabotropic receptor in neurons generates inositol 1,4,5-trisphosphate, which causes the release of Ca2+ from intracellular stores and diacylglycerol, which activates protein kinase C. In nerve terminals, the activation of presynaptic protein kinase C with phorbol esters enhances glutamate release. But the presynaptic receptor involved in this protein kinase C-mediated increase in the release of glutamate has not yet been identified. Here we demonstrate the presence of a presynaptic glutamate receptor of the metabotropic type that mediates an enhancement of glutamate exocytosis in cerebrocortical nerve terminals. Interestingly, this potentiation of glutamate release is observed only in the presence of arachidonic acid, which may reflect that this positive feedback control of glutamate exocytosis operates in concert with other pre- or post-synaptic events of the glutamatergic neurotransmission that generate arachidonic acid. This presynaptic glutamate receptor may have a physiological role in the maintenance of long-term potentiation where there is an increase in glutamate release mediated by postsynaptically generated arachidonic acid.     

Identification of a G1-type cyclin puc1+ in the fission yeast Schizosaccharomyces pombe

In rapidly growing cells of the budding yeast Saccharomyces cerevisiae, the cell cycle is regulated chiefly at Start, just before the G1-S boundary, whereas in the fission yeast Schizosaccharomyces pombe, the cycle is predominantly regulated at G2-M. Both control points are present in both yeasts, and both require the p34cdc2 protein kinase. At G2-M, p34cdc2 kinase activity in S. pombe requires a B-type cyclin in a complex with p34cdc2; this complex is the same as MPF (maturation promoting factor). The p34cdc2 activity at the G1-S transition in S. cerevisiae may be regulated by a similar cyclin complex, using one of the products of a new class of cyclin genes (CLN1, CLN2 and WHI1 (DAF1/CLN3)). At least one is required for progression through the G1-S phase, and deletion of all three leads to G1 arrest. WHI1 was isolated as a dominant allele causing budding yeast cells to divide at a reduced size and was later independently identified as DAF1, a dominant allele of which rendered the cells refractory to the G1-arrest induced by the mating pheromone alpha-factor. The dominant alleles are truncations thought to yield proteins of increased stability, and the cells are accelerated through G1. Without WHI1 function, the cells are hypersensitive to alpha-factor, enlarged and delayed in G1. Heretofore, this G1-class of cyclins has not been identified in other organisms. We have isolated a G1-type cyclin gene called puc1+ from S. pombe, using a functional assay in S. cerevisiae. Expression of puc1+ in S. pombe indicates that it has a cyclin-like role in the fission yeast distinct from the role of the B-type mitotic cyclin.     

S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28.

In somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosine 15 (Y15) of p34cdc2, the protein kinase subunit of maturation promoting factor, accelerate the entry into mitosis and abolish the ability of unreplicated DNA to arrest cells in G2. Because the tyrosine phosphorylation of p34cdc2 is conserved in S. pombe, Xenopus, chicken and human cells, the regulation of p34cdc2-Y15 phosphorylation could be a universal mechanism mediating the S-phase feedback control and regulating the initiation of mitosis. We have investigated these phenomena in the budding yeast Saccharomyces cerevisiae. We report here that the CDC28 gene product (the S. cerevisiae homologue of cdc2) is phosphorylated on the equivalent tyrosine (Y19) during S phase but that mutations that prevent tyrosine phosphorylation do not lead to premature mitosis and do not abolish feedback controls. We have therefore demonstrated a mechanism that does not involve tyrosine phosphorylation of p34 by which cells arrest their division in response to the presence of unreplicated or damaged DNA. We speculate that this mechanism may not involve the inactivation of p34 catalytic activity.     

多重休假的Bernoulli反馈M/G/1排队系统的稳态存在条件

休假排队是经典排队理论的延伸和发展，并已发展成为一个有独立特色的研究方向，形成了以随机分解为核心的基本理论框架。本文系统地研究了多重休假的Bernoulli反馈M／G／1排队模型，这是一类新服务机制的休假排队系统。本文给出了此排队模型的稳态存在的条件。     

Action of brefeldin A blocked by activation of a pertussis-toxin-sensitive G protein.

In many mammalian cells brefeldin A interferes with mechanisms that keep the Golgi appartus separate from the endoplasmic reticulum. The earliest effect of brefeldin A is release of the coat protein beta-COP from the Golgi. This release is blocked by pretreatment with GTP-gamma S or AlF4- (ref. 12). The AlF4- ion activates heterotrimeric G proteins but not proteins of the ras superfamily, suggesting that a heterotrimeric G protein might control membrane transfer from the endoplasmic reticulum to the Golgi. We report here that mastoparan, a peptide that activates heterotrimeric G proteins, promotes binding of beta-COP to Golgi membranes in vitro and antagonizes the effect of brefeldin A on beta-COP in perforated cells and on isolated Golgi membranes. This inhibition is greatly diminished if cells are pretreated with pertussis toxin before perforation. Thus, a heterotrimeric G protein of the Gi/Go subfamily regulates association of coat components with Golgi membranes.     

关于G/G/1排队模型中排队长度的积分

考虑了一个具有中度正则变化服务时间的G/G/1模型.假设Q(t)是排队长度,则在忙期[0,l]上,Q(t)下方所扫过的面积也具有中度正则变化的性质.     

Regulation of the G1-S transition in postembryonic neuronal precursors by axon ingrowth.

In the newly cellularized Drosophila embryo, progress through the cell cycle is regulated at the G2-M transition. We have examined cell-cycle regulation later in Drosophila development, in a group of postembryonic neuronal precursors. The S-phase precursor cells, which generate photoreceptor target neurons (lamina neurons) in the central nervous system, are not present in the absence of photoreceptor innervation. Here we report that axons selectively approach G1-phase precursors. Without axon ingrowth, lamina precursors do not enter their final S phase and by several criteria, arrest in the preceding G1 phase. These findings provide evidence that at this stage in development the control of cell division can occur at the G1-S transition.     

具有二次可选服务反馈的MX/G/1(E,SV)排队系统

研究了批量到达的具有第二次可选择服务且两次服务均可反馈的单重休假排队系统.建立了休假、反馈、可选服务多类型的排队模型.采用补充变量法,首先建立了系统稳态下的状态转移方程,通过求解得到了稳态下系统队长的概率母函数,进而计算出稳态下系统的平均队长.对稳态队长进行分析之后,又给出了稳态队长的随机分解定理,其中给出了附加队长的明确概率解释.     

Catalan方程x~n+1=y~2的正整数解

研究了一类不定方程求正整数解的问题.借助数论中的一些简单结果,推导并证明了Catalan方程xn+1=y2的正整数解的一般公式.Catalan方程xn+1=y2的一切正整数解可表示为(x,y,n)=(k2-1,k,1)或(2,3,3),这里k为大于1的正整数.