Organization of Enzyme Concentration across the Metabolic Network in Cancer Cells

Rapid advances in mass spectrometry have allowed for estimates of absolute concentrations across entire proteomes, permitting the interrogation of many important biological questions. Here, we focus on a quantitative aspect of human cancer cell metabolism that has been limited by a paucity of available data on the abundance of metabolic enzymes. We integrate data from recent measurements of absolute protein concentration to analyze the statistics of protein abundance across the human metabolic network. At a global level, we find that the enzymes in glycolysis comprise approximately half of the total amount of metabolic proteins and can constitute up to 10% of the entire proteome. We then use this analysis to investigate several outstanding problems in cancer metabolism, including the diversion of glycolytic flux for biosynthesis, the relative contribution of nitrogen assimilating pathways, and the origin of cellular redox potential. We find many consistencies with current models, identify several inconsistencies, and find generalities that extend beyond current understanding. Together our results demonstrate that a relatively simple analysis of the abundance of metabolic enzymes was able to reveal many insights into the organization of the human cancer cell metabolic network.     

Insecticidal and Repellent Activity of Siparuna guianensis Aubl. (Negramina) against Aedes aegypti and Culex quinquefasciatus

This study investigated the toxic effects of essential oils isolated from Siparuna guianensis against Aedes aegypti, Culex quinquefasciatus (eggs, larvae, pupae, and adult) and Aedes albopictus (C6/36) cells. The oviposition-deterring activity, egg viability, and repellence activity in the presence of different essential oils concentrations were determined. The essential oils showed high toxicity to all developmental stages of A. aegypti and C. quinquefasciatus. Furthermore, the oils also showed high repellent activity towards the adult stage of mosquitoes (0.025 to 0.550 μg/cm2 skin conferred 100% repellence up to 120 min) and in contact with cultured insect cells (C6/36) induced death possibly by necrosis. The results presented in this work show the potential of S. guianensis essential oils for the development of an alternative and effective method for the natural control of mosquitoes in homes and urban areas.     

Inhibition of Autoimmune Diabetes in NOD Mice by miRNA Therapy

Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes. Treatment of NOD mice with TA1 resulted in a systemic broad-spectrum upregulation of tolerogenic T cell subsets with a parallel downregulation of Teff subsets yielding a dramatic increase in the Treg:Teff ratio. Moreover, the murine-derived TA1 was highly effective in the inhibition of allorecognition of HLA-disparate human PBMC. TA1 demonstrated dose-responsiveness and exhibited equivalent or better inhibition of allorecognition driven proliferation than etanercept (a soluble TNF receptor). These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest autoimmune disease processes and may be of significant utility in a broad range of autoimmune diseases including Type 1 diabetes.     

The detection of two antigenic groups among Renibacterium salmoninarum isolates

The analysis of the membrane proteins and their antigenic properties in a group of 14 geographically diverse strains of Renibacterium salmoninarum revealed the existence of antigenic diversity within this species. Eleven isolates, including the type strain ATCC 33209, shared a similar protein profile with a major component of 57 kDa whereas three strains showed a common pattern with a major protein of 30 kDa. The quantitative agglutination tests and Western blotting assays seem to indicate the existence of serological heterogeneity, with two distinct groups being detected.     

Harder,better, faster,stronger: Weapon size is more sexually dimorphic than weapon biomechanical components in two freshwater anomuran species

Sexual selection influences the evolution of morphological traits that increase the likelihood of monopolizing scarce resources. When such traits are used during contests, they are termed weapons. Given that resources are typically linked to monopolizing mating partners, theory expects only males to bear weapons. In some species, however, females also bear weapons, although typically smaller than male weapons. Understanding why females bear smaller weapons can thus help us understand the selective pressures behind weapon evolution. However, most of our knowledge comes from studies on weapon size, while the biomechanics of weapons, such as the size of the muscles, efficiency, and shape are seldom studied. Our goal was to test if the theoretical expectations for weapon size sexual dimorphism also occur for weapon biomechanics using two aeglid crab species. Males of both species had larger claws which were also stronger than female claws. Male claws were also more efficient than females' claws (although we used only one species in this analysis). For weapon shape, though, only one species differed in the mean claw shape. Regarding scaling differences, in both species, male claws had higher size scaling than females, while only one species had a higher shape scaling. However, male weapons did not have higher scaling regarding strength and efficiency than females. Thus, males apparently allocate more resources in weapons than females, but once allocated, muscle and efficiency follow a similar developmental pathway in both sexes. Taken together, our results show that sexual dimorphism in weapons involves more than differences in size. Shape differences are especially intriguing because we cannot fully understand its causes. Yet, we highlight that such subtle differences can only be detected by measuring and analysing weapon shape and biomechanical components. Only then we might better understand how weapons are forged.     

beta, a novel repetitive DNA element associated with tRNA genes in the pathogenic yeast Candida albicans

We have identified a novel 399 bp repetitive DNA element (which we designate beta  ) 9 bp upstream of a seryl-tRNA_CAG gene in the genome of Candida albicans . There are two copies of the seryl-tRNA_CAG gene, one on each homologue of chromosome VI, and the beta element is found upstream of one copy of the gene in C. albicans strain 2005E. The beta element is not present upstream of either copy of the seryl-tRNA_CAG gene in eight other laboratory strains of C. albicans tested, but was detected in this location in several fresh clinical isolates. Southern blot analysis indicated that there are approximately eight copies of the beta element per diploid C. albicans genome and that it is a mobile element, being present on at least two different chromosomes. Three unique genomic DNA clones containing the beta element were isolated from strain 2005E; in each case, a different tRNA gene was found immediately adjacent to the beta element. Three new tRNA genes from C. albicans have thus been identified: tRNA^Asp, tRNA^Ala and tRNA^Ile. The beta element shows no significant sequence homology to other known prokaryotic or eukaryotic repetitive elements, although an 8 bp repeat at the 3' end of the element is identical to that of the Ty3 retrotransposable element of Saccharomyces cerevisiae . We propose that the beta element is a solo long terminal repeat (LTR) sequence of a Ty3/gypsy-like transposable element in C. albicans that is closely associated with tRNA genes.     

The Interaction between Root Herbivory and Competitive Ability of Native and Invasive-Range Populations of Brassica nigra

The evolution of increased competitive ability (EICA) hypothesis predicts that escape from intense herbivore damage may enable invasive plants to evolve higher competitive ability in the invasive range. Below-ground root herbivory can have a strong impact on plant performance, and invasive plants often compete with multiple species simultaneously, but experimental approaches in which EICA predictions are tested with root herbivores and in a community setting are rare. Here, we used Brassica nigra plants from eight invasive- and seven native-range populations to test whether the invasive-range plants have evolved increased competitive ability when competing with Achillea millefolium and with a community (both with and without A. millefolium). Further, we tested whether competitive interactions depend on root herbivory on B. nigra by the specialist Delia radicum. Without the community, competition with A. millefolium reduced biomass of invasive- but not of native-range B. nigra. With the community, invasive-range B. nigra suffered less than native-range B. nigra. Although the overall effect of root herbivory was not significant, it reduced the negative effect of the presence of the community. The community produced significantly less biomass when competing with B. nigra, irrespective of the range of origin, and independent of the presence of A. millefolium. Taken together, these results offer no clear support for the EICA hypothesis. While native-range B. nigra plants appear to be better in dealing with a single competitor, the invasive-range plants appear to be better in dealing with a more realistic multi-species community. Possibly, this ability of tolerating multiple competitors simultaneously has contributed to the invasion success of B. nigra in North America.