A complex containing the CCR4 and CAF1 proteins is involved in mRNA deadenylation in Drosophila

The CCR4-NOT complex is the major enzyme catalyzing mRNA deadenylation in Saccharomyces cerevisiae. We have identified homologs for almost all subunits of this complex in the Drosophila genome. Biochemical fractionation showed that the two likely catalytic subunits, CCR4 and CAF1, were associated with each other and with a poly(A)-specific 3' exonuclease activity. In Drosophila, the CCR4 and CAF1 proteins were ubiquitously expressed and present in cytoplasmic foci. Individual knock-down of several potential subunits of the Drosophila CCR4-NOT complex by RNAi in tissue culture cells led to a lengthening of bulk mRNA poly(A) tails. Knock-down of two individual subunits also interfered with the rapid deadenylation of Hsp70 mRNA during recovery from heat shock. Similarly, ccr4 mutant flies had elongated bulk poly(A) and a defect in Hsp70 mRNA deadenylation. A minor increase in bulk poly(A) tail length was also observed in Rga mutant flies, which are affected in the NOT2 subunit. The data show that the CCR4-NOT complex is conserved in Drosophila melanogaster and plays a role in general and regulated mRNA deadenylation.     

Increased p21(ras) activity in human fibroblasts transduced with survivin enhances cell proliferation

Survivin is critically involved in mitosis and when overexpressed enhances the activity of the Aurora B kinase, a serine-threonine kinase belonging to the family of oncogenic Aurora/IpI1p-related kinases. Both proteins interact with Ras GTPase-activating protein suggesting an impact on the Ras pathway. This study aimed at defining the role of survivin in proliferation and potential transformation of cells. When survivin was overexpressed in normal human lung fibroblasts, the characteristic track lanes of fibroblasts were disturbed and the rate of cell proliferation was increased. An enhanced level of p21(ras) mRNA and protein expression and concomitant rise in levels of activated p21(ras) were observed. Despite increased proliferation cell survival remained dependent on serum and cells were not able to form colonies in soft agar assays. These data suggest that overexpression of survivin increases cell growth but, despite the increase in active p21(ras), is not sufficient to transform primary cells. Yet, in addition to its anti-apoptotic function it might contribute to the accelerated growth of tumour cells by increasing p21(ras) activity.     

Beitrag zur Kenntnis des Vorkommens ostpal?arktischer Limikolen auf Mindoro, Philippinen

Summary From September 1970 till March 1972 field observations on birds were carried out on the Philippine Island Mindoro Occ., in the vicinity of the town San José. This paper deals with plovers, snipes and waders which were either on the passage, or wintering in that area. A few individuals of ten species probably remain also during sommer season in the Philippines. The evaporation lakes of the Philippine Salt Industry (PSI), the ricefields and fishponds of the adjacent National Investment and Development Corporation (NIDC), including the coast of the South China Sea and two large rivers are an important habitat for these birds. Therefore, 14 additions have been made to the avifaunal list of Mindoro Island.     

A randomised sham controlled trial of vertebroplasty for painful acute osteoporotic vertebral fractures (VERTOS IV)

Background

Combination of erlotinib and bevacizumab is a promising regimen in advanced non-squamous non-small-cell lung cancer (NSCLC). We are conducting a single arm phase II trial which aims to evaluate the efficacy and safety of this regime as a second- or third-line chemotherapy.

Methods

Key eligibility criteria were histologically or cytologically confirmed non-squamous NSCLC, stage III/IV or recurrent NSCLC not indicated radical chemoradiation, prior one or two regimen of chemotherapy, age 20 years or more, and performance status of two or less. The primary endpoint is objective response rate. The secondary endpoints include overall survival, progression-free survival, disease control rate and incidence of adverse events. This trial plans to accrue 80 patients based on a two-stage design employing a binomial distribution with an alternative hypothesis response rate of 35% and a null hypothesis threshold response rate of 20%. A subset analysis according to EGFR mutation status is planned.

Discussion

We have presented the design of a single arm phase II trial to evaluate the efficacy and safety of combination of bevacizumab and erlotinib in advanced non-squamous NSCLC patients. In particular we are interested in determining the merit of further development of this regimen and whether prospective patient selection using EGFR gene is necessary in future trials.

Trial registration

This trial was registered at the UMIN Clinical Trials Registry as UMIN000004255 (http://www.umin.ac.jp/ctr/index.htm).     

A sampling theory for asymmetric communities

We introduce the first analytical model of asymmetric community dynamics to yield Hubbell's neutral theory in the limit of functional equivalence among all species. Our focus centers on an asymmetric extension of Hubbell's local community dynamics, while an analogous extension of Hubbell's metacommunity dynamics is deferred to an appendix. We find that mass-effects may facilitate coexistence in asymmetric local communities and generate unimodal species abundance distributions indistinguishable from those of symmetric communities. Multiple modes, however, only arise from asymmetric processes and provide a strong indication of non-neutral dynamics. Although the exact stationary distributions of fully asymmetric communities must be calculated numerically, we derive approximate sampling distributions for the general case and for nearly neutral communities where symmetry is broken by a single species distinct from all others in ecological fitness and dispersal ability. In the latter case, our approximate distributions are fully normalized, and novel asymptotic expansions of the required hypergeometric functions are provided to make evaluations tractable for large communities. Employing these results in a Bayesian analysis may provide a novel statistical test to assess the consistency of species abundance data with the neutral hypothesis.     

Degradation of hsp70 and other mRNAs in Drosophila via the 5' 3' pathway and its regulation by heat shock

Two general pathways of mRNA decay have been characterized in yeast. Both start with deadenylation. The major pathway then proceeds via cap hydrolysis and 5'-exonucleolytic degradation whereas the minor pathway consists of 3'-exonucleolytic decay followed by hydrolysis of the remaining cap structure. In higher eukaryotes, these pathways of mRNA decay are believed to be conserved but have not been well characterized. We have investigated the decay of the hsp70 mRNA in Drosophila Schneider cells. As shown by the use of reporter constructs, rapid deadenylation of this mRNA is directed by its 3'-untranslated region. The main deadenylase is the CCR4.NOT complex; the PAN nuclease makes a lesser contribution. Heat shock prevents deadenylation not only of the hsp70 but also of bulk mRNA. A completely deadenylated capped hsp70 mRNA decay intermediate accumulates transiently and is degraded via cap hydrolysis and 5'-decay. Thus, decapping is a slow step in the degradation pathway. Cap hydrolysis is also inhibited during heat shock. Degradation of reporter RNAs from the 3'-end became detectable only upon inhibition of 5'-decay and thus represents a minor decay pathway. Because two reporter RNAs and at least two endogenous mRNAs were degraded primarily from the 5'-end with cap hydrolysis as a slow step, this pathway appears to be of general importance for mRNA decay in Drosophila.     

Potential risk of biologic pollution associated to the introduction of <i>Pinus radiata</i> in grassland areas

Afforestation is a recommended practice to mitigate global warming. However, their implementation may generate undesirable impacts, mostly if exotic species are used. Plantations of Pinus radiata D Don in Ventania (Bs. As., Argentina) soils showed notorious increments of extractable P (Pe), which could affect the dynamic of this element as well as the degree of phosphorus saturation (GSP_Bray). The objectives of this study were: i) to quantify the GSP_Bray in Mollisols afforested with P. radiata comparing the results with those coming from adjacent, natural grassland areas (base line); ii) to evaluate the potential environmental risk induced by afforestation through the identification of a change point (PC) in the GSP_Bray indicative of a phosphate leaching increment. Treatments included mature stands of P. radiata (TB) and adjacent areas with natural grassland vegetation (TP). Samples were taken at 0-15; 15-30 and 30-45 cm soil depth, and texture, pH, total organic carbon (COT), Pe, soluble reactive phosphorus (PSR), phosphorus sorption index (ISP) and GSP_Bray were determined. The results showed a significant acidification in TB and an increase in the COT stock, indicating an additional atmospheric CO₂ sequestration by the trees. The Pe and PSR values were notoriously higher in TB, and they were reflected in a significant increment in the GSP_Bray with respect to TP. The detection of a significant PC in the GSP_Bray-PSR regression indicates higher chances of phosphate leaching in the forest stands, which could reach water courses, lakes and artificial reservoirs promoting their eutrophication. Because of the potential environmental pollution risk of biologic origin derived from the afforestation with P. radiata in Mollisols areas, their inclusion in clean development practices must be reconsidered.     

Critical conditions for phytoplankton blooms

We motivate and analyse a reaction—advection—diffusion model for the dynamics of a phytoplankton species. The reproductive rate of the phytoplankton is determined by the local light intensity. The light intensity decreases with depth due to absorption by water and phytoplankton. Phytoplankton is transported by turbulent diffusion in a water column of given depth. Furthermore, it might be sinking or buoyant depending on its specific density. Dimensional analysis allows the reduction of the full problem to a problem with four dimensionless parameters that is fully explored. We prove that the critical parameter regime for which a stationary phytoplankton bloom ceases to exist, can be analysed by a reduced linearized equation with particular boundary conditions. This problem is mapped exactly to a Bessel function problem, which is evaluated both numerically and by asymptotic expansions. A final transformation from dimensionless parameters back to laboratory parameters results in a complete set of predictions for the conditions that allow phytoplankton bloom development. Our results show that the conditions for phytoplankton bloom development can be captured by a critical depth, a compensation depth, and zero, one or two critical values of the vertical turbulent diffusion coefficient. These experimentally testable predictions take the form of similarity laws: every plankton—water—light-system characterized by the same dimensionless parameters will show the same dynamics.