An Insertion Peptide in Yeast Glycyl-tRNA Synthetase Facilitates both Productive Docking and Catalysis of Cognate tRNAs

The yeast Saccharomyces cerevisiae possesses two distinct glycyl-tRNA synthetase (GlyRS) genes: GRS1 and GRS2. GRS1 is dually functional, encoding both cytoplasmic and mitochondrial activities, while GRS2 is dysfunctional and not required for growth. The protein products of these two genes, GlyRS1 and GlyRS2, are much alike but are distinguished by an insertion peptide of GlyRS1, which is absent from GlyRS2 and other eukaryotic homologues. We show that deletion or mutation of the insertion peptide modestly impaired the enzyme''s catalytic efficiency in vitro (with a 2- to 3-fold increase in K_m and a 5- to 8-fold decrease in k_cat). Consistently, GRS2 can be conveniently converted to a functional gene via codon optimization, and the insertion peptide is dispensable for protein stability and the rescue activity of GRS1 at 30°C in vivo. A phylogenetic analysis further showed that GRS1 and GRS2 are paralogues that arose from a gene duplication event relatively recently, with GRS1 being the predecessor. These results indicate that GlyRS2 is an active enzyme essentially resembling the insertion peptide-deleted form of GlyRS1. Our study suggests that the insertion peptide represents a novel auxiliary domain, which facilitates both productive docking and catalysis of cognate tRNAs.     

Cytochrome P450 2E1-derived reactive oxygen species mediate paracrine stimulation of collagen I protein synthesis by hepatic stellate cells.

To evaluate possible fibrogenic effects of CYP2E1-dependent generation of reactive oxygen species, a model was developed using co-cultures of HepG2 cells, which do (E47 cells) or do not (C34 cells) express cytochrome P450 2E1 (CYP2E1) with stellate cells. There was an increase in intra- and extracellular H(2)O(2), lipid peroxidation, and collagen type I protein in stellate cells co-cultured with E47 cells compared with stellate cells alone or co-cultured with C34 cells. The increase in collagen was prevented by antioxidants and a CYP2E1 inhibitor. CYP3A4 did not mimic the stimulatory effects found with CYP2E1. Collagen mRNA levels remained unchanged, and pulse-chase analysis indicated similar half-lives of collagen I protein between both co-cultures. However, collagen protein synthesis was increased in E47 co-culture. Hepatocytes from pyrazole-treated rats (with high levels of CYP2E1) induced collagen protein in primary stellate cells, and antioxidants and CYP2E1 inhibitors blocked this effect. These results suggest that increased translation of collagen mRNA by CYP2E1-derived reactive oxygen species is responsible for the increase in collagen protein produced by the E47 co-culture. These co-culture models may be useful for understanding the impact of CYP2E1-derived ROS on stellate cell function and activation.     

Identifying common prognostic factors in genomic cancer studies: A novel index for censored outcomes

Background  

With the growing number of public repositories for high-throughput genomic data, it is of great interest to combine the results produced by independent research groups. Such a combination allows the identification of common genomic factors across multiple cancer types and provides new insights into the disease process. In the framework of the proportional hazards model, classical procedures, which consist of ranking genes according to the estimated hazard ratio or the p-value obtained from a test statistic of no association between survival and gene expression level, are not suitable for gene selection across multiple genomic datasets with different sample sizes. We propose a novel index for identifying genes with a common effect across heterogeneous genomic studies designed to remain stable whatever the sample size and which has a straightforward interpretation in terms of the percentage of separability between patients according to their survival times and gene expression measurements.     

Pattern analysis of stem cell differentiation during <Emphasis Type="Italic">in vitro Arabidopsis</Emphasis> organogenesis

Plant somatic cells have the capability to switch their cell fates from differentiated to undifferentiated status under proper culture conditions, which is designated as totipotency. As a result, plant cells can easily regenerate new tissues or organs from a wide variety of explants. However, the mechanism by which plant cells have such remarkable regeneration ability is still largely unknown. In this study, we used a set of meristem-specific marker genes to analyze the patterns of stem cell differentiation in the processes of somatic embryogenesis as well as shoot or root organogenesis in vitro. Our studies furnish preliminary and important information on the patterns of the de novo stem cell differentiation during various types of in vitro organogenesis.     

Reassessing Neotropical angiosperm distribution patterns based on monographic data: a geometric interpolation approach

Monographic data rely on specimens deposited in herbaria and museums, which have been thoroughly revised by experts. However, monographic data have been rarely used to map species richness at large scale, mainly because of the difficulties caused by spatially heterogeneous sampling effort. In this paper we estimate patterns of species richness and narrow endemism, based on monographic data of 4,055 Neotropical angiosperm species. We propose a geometric interpolation method to derive species ranges at a 1° grid resolution. To this we apply an inverse distance-weighted summation scheme to derive maps of species richness and endemism. In the latter we also adjust for heterogeneous sampling effort. Finally, we test the robustness of the interpolated species ranges and derived species richness by applying the same method but using a leave-one-out-cross-validation (LOOCV). The derived map shows four distinct regions of elevated species richness: (1) Central America, (2) the Northern Andes, (3) Amazonia and (4) the Brazilian Atlantic coast (‘Mata Atlantica’). The region with the highest estimated species richness is Amazonia, with Central America following closely behind. Centers of narrow endemism are located over the entire Neotropics, several of them coinciding with regions of elevated species richness. Sampling effort has a minor influence on the interpolation of overall species richness, but it substantially influences the estimation of regions of narrow endemism. Thus, in order to improve maps of narrow endemism and resulting conservation efforts, more collection and identification activity is required.     

Gentamicin and amikacin repress the growth of Plasmodium falciparum in culture, probably by inhibiting a parasite acid phospholipase

Human erythrocytes were loaded with either gentamicin or amikacin and subsequently infected with the human malarial parasite Plasmodium falciparum and grown in culture. Parasite invasion of erythrocytes was unaffected by the drugs, but subsequent development was retarded. The digestion of host cell cytosol in ring-stage parasites was inhibited by the drugs. A substantial acid, Ca2+-independent phospholipase activity could be monitored in parasite cytosol and was found to be inhibited by the drugs. These results imply that phospholipases are involved in the feeding mechanism of the parasite and that gentamicin and amikacin exert their inhibitory activity by affecting these enzymes.     

On the Robustness of the Geometrical Model for Cell Wall Deposition

All plant cells are provided with the necessary rigidity to withstand the turgor by an exterior cell wall. This wall is composed of long crystalline cellulose microfibrils embedded in a matrix of other polysaccharides. The cellulose microfibrils are deposited by mobile membrane bound protein complexes in remarkably ordered lamellar textures. The mechanism by which these ordered textures arise, however, is still under debate. The geometrical model for cell wall deposition proposed by Emons and Mulder (Proc. Natl. Acad. Sci. 95, 7215–7219, 1998) provides a detailed approach to the case of cell wall deposition in non-growing cells, where there is no evidence for the direct influence of other cellular components such as microtubules. The model successfully reproduces even the so-called helicoidal wall; the most intricate texture observed. However, a number of simplifying assumptions were made in the original calculations. The present work addresses the issue of the robustness of the model to relaxation of these assumptions, by considering whether the helicoidal solutions survive when three aspects of the model are varied. These are: (i) the shape of the insertion domain, (ii) the distribution of lifetimes of individual CSCs, and (iii) fluctuations and overcrowding. Although details of the solutions do change, we find that in all cases the overall character of the helicoidal solutions is preserved.     

New Intercommunity Infanticides by the Chimpanzees of Ngogo,Kibale National Park,Uganda

Hostile intercommunity relations, including attacking and killing extra-community infants of both sexes have occurred at most wild chimpanzee sites. We describe three recent cases of intercommunity attacks on infants committed by members of the Ngogo chimpanzee community in Kibale National Park, Uganda. Two of the attacks resulted in confirmed infanticides while a third attack probably resulted in the infant's death. In common with previous accounts of chimpanzee infanticides, the attacks described here occurred during boundary patrols outside the Ngogo community's usual range, adult and adolescent males were the main participants, one infant was cannibalized after being killed, and the victims’ mothers did not accompany the attacking party back to the Ngogo range. However, the patrol parties during each infanticide were larger than before and included females from the Ngogo community. Our observations indirectly support both the range expansion and imbalance of power hypotheses, which address why and under which conditions chimpanzee intercommunity encounters lead to aggression. These cases of intercommunity infanticide add to the growing database of the phenomenon in wild chimpanzees.     

Pendelluft flow in symmetric airway bifurcations.

We propose a mathematical model for pendelluft flow in a single airway bifurcation. The model is motivated by an apparatus used in an experimental study of the pendelluft by Ultman et al. (1988). We derive differential equations governing the fluid flow, which directly connect physiological parameters to the variables determining the pendelluft; this approach allows us to include nonlinearity in the model. If nonlinearity is neglected, our model is identical to the R-I-C circuits used by previous investigators. If nonlinearity is retained, we show that pendelluft can occur even in perfectly symmetric airway bifurcations. For the specific apparatus used in the experiments of High et al. (1991), we demonstrate that two qualitatively different pendelluft flows can occur in the system.