Stoichiometry of bacterial anaerobic oxidation of elemental sulfur by ferric iron

The conventional stoichiometry of the oxidation of elemental sulfur by ferric iron in Acidithiobacillus ferrooxidans was not in agreement with our experimental data in terms of ferrous iron and proton formation. Reaction modelling under the actual conditions of bacterial activity resulted in a different stoichiometry, where additional iron species participate in the process to affect the number of released protons. The suggested reaction equation may more accurately predict the intensity of environmental acidification during the anaerobic bioprocess.     

Crown age estimation of a monocotyledonous tree species Dracaena cinnabari using logistic regression

Unique woodlands of Dracaena cinnabari (DC) are at risk throughout most of their range (Socotra Island, Yemen) as a result of missing regeneration and overmaturity. Effective conservation measures depend on reliable predictions of future population dynamics, which depend on accurate data on current age structure. However, age determination of Dracaena sp. has long been a scientific challenge, because the common method of tree ring counts cannot be applied to this or to most other monocotyledonous trees. In the present study, the indirect method for crown age estimation proposed by Adolt and Pavlis (Trees 18:43–53, 2004) was further developed using a more appropriate statistical technique and an intuitive model formulation. This new technique is based on the relationship between the number of branching orders and the number of flowering events that result from a specific growth pattern. We used logistic regression to directly model annual flowering probability, the reciprocal value of which corresponds to the length of the interval between flowering events. Our methodology was applied to data sets collected at two ecologically distinct sites. In Firmihin, the time between flowering events decreases from 28?years between the first and second event to 10?years between the 25th and 26th event. The length of time between flower events in Skant, however, was estimated to be a constant value of 6.5?years. We propose the application of generalised mixed-effects models and methods of survey sampling to improve the accuracy of crown age estimation in DC. Our methodology may also be useful for age estimations of other tree species with similar growth patterns, such as Dracaena draco and Aloe dichotoma.     

Plant Aurora kinases play a role in maintenance of primary meristems and control of endoreduplication

? The conserved family of Aurora kinases has multiple functions during mitosis. The roles of plant Aurora kinases have been characterized using inhibitor treatments. ? We down-regulated Aurora kinases in Arabidopsis thaliana using RNA interference (RNAi). We carried out a detailed phenotypic analysis of Aurora RNAi plants, biochemical and microscopic studies of AtAurora1 kinase together with AtTPX2 (targeting protein for Xklp2) and γ-tubulin. ? Cell division defects were observed in plants with reduced expression of Aurora kinases. Furthermore, the maintenance of primary meristems was compromised and RNAi seedlings entered endoreduplication prematurely. AtAurora1, its activator AtTPX2, and γ-tubulin were associated with microtubules in vitro; they were attached to regrowing kinetochore microtubules and colocalized on spindle microtubules and with a subset of early phragmoplast microtubules. Only the AtAurora1 kinase was translocated to the area of the cell plate. ? RNAi silencing of Aurora kinases showed that, in addition to their function in regulating mitosis, the kinases are required for maintaining meristematic activity and controlling the switch from meristematic cell proliferation to differentiation and endoreduplication. The colocalization and co-fractionation of AtAurora1 with AtTPX2, and γ-tubulin on microtubules in a cell cycle-specific manner suggests that AtAurora1 kinase may function to phosphorylate substrates that are critical to the spatiotemporal regulation of acentrosomal microtubule formation and organization.     

The roles of G proteins in the activation of TRPC4 and TRPC5 transient receptor potential channels

TRPC4 and TRPC5 channels are important regulators of electrical excitability in both gastrointestinal myocytes and neurons. Much is known regarding the assembly and function of these channels including TRPC1 as a homotetramer or a heteromultimer and the roles that their interacting proteins play in controlling these events. Further, they are one of the best-studied targets of G protein-coupled receptors and growth factors in general and Gαq protein coupled receptor or epidermal growth factor in particular. However, our understanding of the roles of Gαi/o proteins on TRPC4/5 channels is still rudimentary. We discuss potential roles for Gαi/o proteins in channel activation in addition to their known role in cellular signaling.     

Exploring the Plasmodium falciparum cyclic-adenosine monophosphate (cAMP)-dependent protein kinase (PfPKA) as a therapeutic target

One of the prototype mammalian kinases is PKA and various roles have been defined for PKA in malaria pathogenesis. The recently described phospho-proteomes of Plasmodium falciparum introduced a great volume of phospho-peptide data for both basic research and identification of new anti-malaria therapeutic targets. We discuss the importance of phosphorylations detected in vivo at different sites in the parasite R and C subunits of PKA and highlight the inhibitor sites in the parasite R subunit. The N-terminus of the parasite R subunit is predicted to be very flexible and we propose that phosphorylation at multiple sites in this region likely represent docking sites for interactions with other proteins, such as 14-3-3. The most significant observation when the P. falciparum C subunit is compared to mammalian C isoforms is lack of phosphorylation at a key site tail implying that parasite kinase activity is not regulated so tightly as mammalian PKA. Phosphorylation at sites in the activation loop could be mediating a number of processes from regulating parasite kinase activity, to mediating docking of other proteins. The important differences between Plasmodium and mammalian PKA isoforms that indicate the parasite kinase is a valid anti-malaria therapeutic target.     

Pipecolic Acid,an Endogenous Mediator of Defense Amplification and Priming,Is a Critical Regulator of Inducible Plant Immunity

Metabolic signals orchestrate plant defenses against microbial pathogen invasion. Here, we report the identification of the non-protein amino acid pipecolic acid (Pip), a common Lys catabolite in plants and animals, as a critical regulator of inducible plant immunity. Following pathogen recognition, Pip accumulates in inoculated Arabidopsis thaliana leaves, in leaves distal from the site of inoculation, and, most specifically, in petiole exudates from inoculated leaves. Defects of mutants in AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1) in systemic acquired resistance (SAR) and in basal, specific, and β-aminobutyric acid–induced resistance to bacterial infection are associated with a lack of Pip production. Exogenous Pip complements these resistance defects and increases pathogen resistance of wild-type plants. We conclude that Pip accumulation is critical for SAR and local resistance to bacterial pathogens. Our data indicate that biologically induced SAR conditions plants to more effectively synthesize the phytoalexin camalexin, Pip, and salicylic acid and primes plants for early defense gene expression. Biological priming is absent in the pipecolate-deficient ald1 mutants. Exogenous pipecolate induces SAR-related defense priming and partly restores priming responses in ald1. We conclude that Pip orchestrates defense amplification, positive regulation of salicylic acid biosynthesis, and priming to guarantee effective local resistance induction and the establishment of SAR.     

Cellular noise regulons underlie fluctuations in Saccharomyces cerevisiae

Stochasticity is a hallmark of cellular processes, and different classes of genes show large differences in their cell-to-cell variability (noise). To decipher the sources and consequences of this noise, we systematically measured pairwise correlations between large numbers of genes, including those with high variability. We find that there is substantial pathway variability shared across similarly regulated genes. This induces quantitative correlations in the expression of functionally related genes such as those involved in the Msn2/4 stress response pathway, amino-acid?biosynthesis, and mitochondrial maintenance. Bioinformatic analyses and genetic perturbations suggest that fluctuations in PKA and Tor signaling contribute to pathway-specific variability. Our results argue that a limited number of well-delineated "noise regulons" operate across a yeast cell and that such coordinated fluctuations enable a stochastic but coherent induction of functionally related genes. Finally, we show that pathway noise is a quantitative tool for exploring pathway features and regulatory relationships in un-stimulated systems.     

Immunotherapy for malignant melanoma

Treatment of metastatic melanoma is a challenge for clinicians as most agents have failed to demonstrate improved survival in phase III trials. Despite the immunogenicity of this tumor entity, different immunological interventions including cytokine therapy, vaccination, biochemotherapy or allogeneic hematopoietic cell transplantation did not lead to a satisfactory response. However, continuous investigation on the immune mediated rejection of melanoma cells has led to the development of effective antibodies blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4), a critical negative regulator of the antitumor T-cell response. Based on data from rodent models, the anti-CTLA-4 antibody ipilimumab was developed into clinical studies where it had encouraging activity in advanced melanoma with unusual response patterns. As in most immunostimulatory therapies, acute toxicities were severe and clearly mechanism-related. Although some patients developed signs of autoimmunity, the toxicities were overall manageable and mostly reversible. This review summarizes different immunotherapeutical approaches against melanoma that have been applied in the past and focuses on CTLA-4 blockade with respect to its mechanism, clinical effectiveness and immunological side effects.