Peptide deformylase of eukaryotic protists: a target for new antiparasitic agents?

Peptide deformylase is found only in Eubacteria, making it a logical target for discovering new antibacterial agents. Although this protein is absent from animal or fungal cells, evidence supports its existence in eukaryotic protists, including the causative agents of malaria, sleeping sickness, Chagas disease and leishmaniosis. Here, Thierry Meinnel discusses the idea that deformylase inhibitors could be used as very broad-spectrum antibiotics against bacterial infections, as well as parasitic diseases.     

Plant improvement for tolerance to aluminum in acid soils – a review

Development of acid soils that limit crop production is an increasing problem worldwide. Many factors contribute to phytotoxicity of these soils, however, in acid soils with a high mineral content, aluminum (Al) is the major cause of toxicity. The target of Al toxicity is the root tip, in which Al exposure causes inhibition of cell elongation and cell division, leading to root stunting accompanied by reduced water and nutrient uptake. Natural variation for Al tolerance has been identified in many crop species and in some crops tolerance to Al has been introduced into productive, well-adapted varieties. Aluminum tolerance appears to be a complex multigenic trait. Selection methodology remains a limiting factor in variety development as all methods have particular drawbacks. Molecular markers have been associated with Al tolerance genes or quantitative trait loci in Arabidopsis and in several crops, which should facilitate development of additional tolerant varieties. A variety of genes have been identified that are induced or repressed upon Al exposure. Most induced genes characterized so far are not specific to Al exposure but are also induced by other stress conditions. Ectopic over-expression of some of these genes has resulted in enhanced Al tolerance. Additionally, expression of genes involved in organic acid synthesis has resulted in enhanced production of organic acids and an associated increase in Al tolerance. This review summarizes the three main approaches that have been taken to develop crops with Al tolerance: recurrent selection and breeding, development of Al tolerant somaclonal variants and ectopic expression of transgenes to reduce Al uptake or limit damage to cells by Al.     

PCAS – a precomputed proteome annotation database resource

Background  

Many model proteomes or "complete" sets of proteins of given organisms are now publicly available. Much effort has been invested in computational annotation of those "draft" proteomes. Motif or domain based algorithms play a pivotal role in functional classification of proteins. Employing most available computational algorithms, mainly motif or domain recognition algorithms, we set up to develop an online proteome annotation system with integrated proteome annotation data to complement existing resources.     

Is Pneumocystis a Plant?

Pneumocystis, an AIDS-associated opportunistic pathogen of the lung has some unusual features. This article focuses on work done by my group to understand the organism's distinct sterols. Although Pneumocystis is closely related to fungi, it lacks the major fungal sterol, ergosterol. Several delta(7) 24-alkysterols synthesized by P. carinii are the same as those reported in some basidiomycete rust fungi. The 24-alkylsterols are synthesized by the action of S-adenosyl-L-methionine:C-24 sterol methyl transferase (SAM:SMT). Fungal SAM:SMT enzymes normally transfer only one methyl group to the C-24 position of the sterol side chain and the cells accumulate C28 24-alkylsterols. In contrast, the P. carinii SAM:SMT and those of some plants catalyze one or two methyl transfer reactions producing both C28 and C29 24-alkylsterols. However, unlike most fungi, plants, and the kinetoplastid flagellates Leishmania and Trypanosoma cruzi, P. carinii does not appear to form double bonds at C-5 of the sterol nucleus and C-22 of the sterol side chain. Furthermore, the P. carinii SAM:SMT substrate preference for C30 lanosterol differs from that of homologous enzymes in any other organisms studied. C31 24-Methylenelanosterol and C32 pneumocysterol, products of SAM:SMT activity on lanosterol, can accumulate in high amounts in some, but not all, human-derived Pneumocystis jiroveci populations.     

The rhizosphere microbiome: Plant–microbial interactions for resource acquisition

While horticulture tools and methods have been extensively developed to improve the management of crops, systems to harness the rhizosphere microbiome to benefit plant crops are still in development. Plants and microbes have been coevolving for several millennia, conferring fitness advantages that expand the plant’s own genetic potential. These beneficial associations allow the plants to cope with abiotic stresses such as nutrient deficiency across a wide range of soils and growing conditions. Plants achieve these benefits by selectively recruiting microbes using root exudates, positively impacting their nutrition, health and overall productivity. Advanced knowledge of the interplay between root exudates and microbiome alteration in response to plant nutrient status, and the underlying mechanisms there of, will allow the development of technologies to increase crop yield. This review summarizes current knowledge and perspectives on plant–microbial interactions for resource acquisition and discusses promising advances for manipulating rhizosphere microbiomes and root exudation.     

Repositioning drugs for inflammatory disease – fishing for new anti-inflammatory agents

Inflammation is an important and appropriate host response to infection or injury. However, dysregulation of this response, with resulting persistent or inappropriate inflammation, underlies a broad range of pathological processes, from inflammatory dermatoses to type 2 diabetes and cancer. As such, identifying new drugs to suppress inflammation is an area of intense interest. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat inflammation. Traditional drug discovery, including structure-based drug design, have largely fallen short of satisfying this unmet need. With faster development times and reduced safety and pharmacokinetic uncertainty, drug repositioning – the process of finding new uses for existing drugs – is emerging as an alternative strategy to traditional drug design that promises an improved risk-reward trade-off. Using a zebrafish in vivo neutrophil migration assay, we undertook a drug repositioning screen to identify unknown anti-inflammatory activities for known drugs. By interrogating a library of 1280 approved drugs for their ability to suppress the recruitment of neutrophils to tail fin injury, we identified a number of drugs with significant anti-inflammatory activity that have not previously been characterized as general anti-inflammatories. Importantly, we reveal that the ten most potent repositioned drugs from our zebrafish screen displayed conserved anti-inflammatory activity in a mouse model of skin inflammation (atopic dermatitis). This study provides compelling evidence that exploiting the zebrafish as an in vivo drug repositioning platform holds promise as a strategy to reveal new anti-inflammatory activities for existing drugs.KEY WORDS: Drug repositioning, Zebrafish, Inflammation, Neutrophil, Atopic dermatitis, Immunity     

Desert ants: is active locomotion a prerequisite for path integration?

Desert ants Cataglyphis fortis have been shown to be able to employ two mechanisms of distance estimation: exploiting both optic flow and proprioceptive information. This study aims at understanding possible interactions between the two possibly redundant mechanisms of distance estimation. We ask whether in Cataglyphis the obviously minor contribution of optic flow would increase or even take over completely if the ants were deprived of reliable proprioceptive information. In various experimental paradigms ants were subjected to passive horizontal displacements during which they perceived optic flow, but were prohibited from active locomotion. The results show that in desert ants active locomotion is essential for providing the ants’ odometer and hence its path integrator with the necessary information.     

Is the Cytosolic Pi Concentration a Limiting Factor for Plant Cell Respiration?

The substrate-dependent O₂ uptake by sycamore (Acer pseudoplatanus L.) cell mitochondria in the presence of ADP and limiting Pi concentrations has been measured. The Pi concentration for half-maximum O₂ uptake rate was found to be in the range 20 to 50 micromolar for all the substrates tested. ³¹P NMR of intact sycamore cells indicated that the Pi concentration in the cytoplasm was in the range 5 to 6 millimolar, approximately 100-fold higher than the Pi concentration required for maximum O₂ uptake rates by isolated mitochondria. When sycamore cells were transferred to a culture medium devoid of Pi, the cytoplasmic Pi concentration decreased from 6 to less than 3 millimolar, but the intact cell respiration remained practically constant for at least 4 days. These results strongly suggest that, in vivo, the respiration rate of sycamore cells is not limited by the quantity of Pi supplied to the mitochondria.     

Leghemoglobin: Different roles for different components?

The ratio of leghemoglobin c content to leghemoglobin a content in soybean (Glycine max) root nodules drops in the early stages of plant growth and becomes constant during flowering and fruiting. These data bring into question the assumption that leghemoglobin components have a single biochemical role in nitrogen fixation.     

An ESS for the Height of a Plant Population, or an Optimal Height for an Individual?—Rethinking Game-Theoretic Models for Plant Height

Plants only interact with neighbors over restricted distances, so local conditions are of great significance for plants. It is therefore important to consider spatial structure and neighborhood effects if we are to understand plants' strategies. We constructed a spatially-explicit, game theory model to explore optimal height growth at the individual-level. In the model, there is no ESS for height growth at the population level, because there is an “instantaneous” optimal height growth strategy for the individual plant that changes depending on the local light environment. The optimal strategy is plasticity in response to local conditions. Game-theoretic models for plant phenotypic traits should move from “mean-field approximations” towards explicit modeling of local interactions.     

tacg – a grep for DNA

Background  

Pattern matching is the core of bioinformatics; it is used in database searching, restriction enzyme mapping, and finding open reading frames. It is done repeatedly over increasingly long sequences, thus codes must be efficient and insensitive to sequence length. Such patterns of interest include simple motifs with IUPAC degeneracies, regular expressions, patterns allowing mismatches, and probability matrices.     

Plant sex chromosomes: a non-degenerated Y?

Animal Y chromosomes have undergone chromosome-wide degeneration in response to a lack of recombination, and ancient Ys contain few functional genes. Recent research suggests that plant Y chromosomes may evolve differently and retain most of their ancestral genes.