Quorum sensing inhibitors as antipathogens: biotechnological applications

The mechanisms through which microbes communicate using signal molecules has inspired a great deal of research. Microbes use this exchange of information, known as quorum sensing (QS), to initiate and perpetuate infectious diseases in eukaryotic organisms, evading the eukaryotic defense system by multiplying and expressing their pathogenicity through QS regulation. The major issue to arise from such networks is increased bacterial resistance to antibiotics, resulting from QS-dependent mediation of the formation of biofilm, the induction of efflux pumps, and the production of antibiotics. QS inhibitors (QSIs) of diverse origins have been shown to act as potential antipathogens. In this review, we focus on the use of QSIs to counter diseases in humans as well as plants and animals of economic importance. We also discuss the challenges encountered in the potential applications of QSIs.     

Correction to: External Supplement of Impulsive Micromanager Trichoderma Helps in Combating CO2 Stress in Rice Grown Under FACE

Plant Molecular Biology Reporter - The original version of this article unfortunately contained missing information at author’s affiliations. The affiliation address of the author’s...     

Replication-mediated instability of the GAA triplet repeat mutation in Friedreich ataxia

Friedreich ataxia is caused by the expansion of a polymorphic and unstable GAA triplet repeat in the FRDA gene, but the mechanisms for its instability are poorly understood. Replication of (GAA•TTC)_n sequences (9–105 triplets) in plasmids propagated in Escherichia coli displayed length- and orientation-dependent instability. There were small length variations upon replication in both orientations, but large contractions were frequently observed when GAA was the lagging strand template. DNA replication was also significantly slower in this orientation. To evaluate the physiological relevance of our findings, we analyzed peripheral leukocytes from human subjects carrying repeats of similar length (8–107 triplets). Analysis of 9400 somatic FRDA molecules using small-pool PCR revealed a similar mutational spectrum, including large contractions. The threshold length for the initiation of somatic instability in vivo was between 40 and 44 triplets, corresponding to the length of a eukaryotic Okazaki fragment. Consistent with the stabilization of premutation alleles during germline transmission, we also found that instability of somatic cells in vivo and repeats propagated in E.coli were abrogated by (GAGGAA)_n hexanucleotide interruptions. Our data demonstrate that the GAA triplet repeat mutation in Friedreich ataxia is destabilized, frequently undergoing large contractions, during DNA replication.     

Genetic admixture of European FRDA genes is the cause of Friedreich ataxia in the Mexican population

Friedreich ataxia accounts for approximately 75% of European recessive ataxia patients. Approximately 98% of pathogenic chromosomes have large expansions of a GAA triplet repeat in the FRDA gene (E alleles), and strong linkage disequilibrium among polymorphisms spanning the FRDA locus indicates a common origin for all European E alleles. In contrast, we found that only 14 of 151 (9.3%) Mexican Mestizo patients with recessive ataxia were homozygous for E alleles. Analysis of polymorphisms spanning the FRDA locus revealed that all Mestizo E alleles had the common European haplotype, indicating that they share a single origin. Genetic admixture levels were determined, which revealed that the relative contributions to the Mestizo FRDA gene pool by Native American and European genes were 76-87% and 13-24%, respectively, commensurate with the observed low prevalence of Friedreich ataxia in Mestizos. This indicates that Friedreich ataxia in Mexican Mestizos is due to genetic admixture of European mutant FRDA genes in the Native American gene pool that existed prior to contact with Europeans.     

The effect of duration and time of food availability on the photoperiodic response in the male house sparrow, Passer domesticus

We investigated the effects of food availability on the seasonal testicular growth in the photoperiodic house sparrow (Passer domesticus). Two experiments were performed, each lasting 4 weeks. In experiment 1, sparrows were exposed to natural (NDL; group 1), short (8L:16D; group 2) and long (16L:8D; groups 3-5) day lengths with access to food ad libitum (groups 1-3) or for 10 h (zeitgeber time (zt) 0-10, group 4; zt 0 is the time of light onset) or for 8 h (zt 8-16, group 5). Testes recrudesced under long, but not short and natural, day lengths, and the recrudescence under long days was influenced by the duration of food availability. In experiment 2, the sparrows were exposed to short (8L:16D, group 1) and long (16L:8D, groups 2-5) day lengths with access to food ad libitum (for groups 1 and 2) or for 6 h (for groups 3-5) at different times during the 16 h light period (group 3- zt 0-6, group 4- zt 5-11, group 5- zt 10-16). As the expected, the testes recrudesced only under long lengths, but the photoinduction was variable among the 4 groups. The testes grew to full size in groups 2 and 3 that received food either ad libitum or for 6 h at zt 0-6, but to sub-maximal size in the groups that received 6 h food either at zt 5-11 (group 4) or at zt 10-16 (group 5). Altogether, these results support the idea that the photoperiodic regulation of reproduction in a seasonally breeding species is influenced both by the duration and the time of food availability.     

Human embryonic kidney cells (HEK-293 cells): characterization and dose-response relationship for modulated release of nerve growth factor for nerve regeneration

The development of engineered constructs to bridge nerve gaps may hold the key to improved functional outcomes in the repair of injured peripheral nerves. These constructs must be rendered bioactive by providing the growth factors required for successful peripheral nerve regeneration. Previous studies demonstrated that harvested human and rat dermal fibroblasts could be genetically engineered to release nerve growth factor (NGF) both in vitro and in vivo. The use of fibroblasts, however, has the potential to cause scarring, and the expression of NGF from those cells was transient. To overcome these potential difficulties, human embryonic kidney cells were modified for use with the ecdysone-inducible mammalian expression system. These cells (hNGF-EcR-293) have been engineered and regulated to secrete human NGF in response to the ecdysone analogue ponasterone A. HEK-293 cells were transfected with human NGF cDNA with the ecdysone-inducible mammalian expression system (Invitrogen, Carlsbad, Calif.). Stable clones were then selected. Ponasterone A, an analogue of ecdysone, was used as the inducing agent. The secretion of NGF into the medium was analyzed with two different methods. After 24 hours of exposure to the inducing agent, cell medium was transferred to PC-12 cells seeded in 12-well plates, for determination of whether the secreted NGF was bioactive. Medium from untreated or ponasterone A-treated hNGF-EcR-293 cells was deemed bioactive on the basis of its ability to induce PC-12 cell differentiation. The concentrations of secreted NGF were also quantified with an enzyme-linked immunosorbent assay, in triplicate. NGF production was measured in successive samples of the same medium during a 9-day period, with maximal release of 9.05 +/- 2.6 ng/ml at day 9. Maximal NGF production was 8.46 +/- 2.1 pg/10(3) cells at day 9. These levels were statistically significantly different from levels in noninduced samples (p 相似文献   

Inorganic salts influence IAA ionization and adventitious rhizogenesis in Pongamia pinnata

The basal cut end of coppice shoot cuttings of Pongamia pinnata was treated for 24 h with 0 (water treated control) or 5.0 mmol/L of KMnO4, KCI, and KH2PO4 or 2.5 mmol/L of K2HPO4 and K2SO4. Inorganic salts of P, S, Cl and Mn significantly influenced IAA ionization and adventitious rhizogenesis. P and S salts had lower IAA ionization potential, but more pronounced effect on adventitious rhizogenesis than Cl and Mn salts. The linear regression analysis also established negative correlations between salt induced IAA ionization with various characteristics of adventitious rhizogenesis such as sprouting (r = -0.83, p < 0.05), rooting (r = -0.82, p < 0.05), root number (r = -0.95, p < 0.01), and root length (r = -0.80, p < 0.1). The implication of IAA ionization in adventitious rhizogenesis has been discussed and the possible role of inorganic salts therein suggested.     

A model-based optimization framework for the inference on gene regulatory networks from DNA array data

MOTIVATION: Identification of the regulatory structures in genetic networks and the formulation of mechanistic models in the form of wiring diagrams is one of the significant objectives of expression profiling using DNA microarray technologies and it requires the development and application of identification frameworks. RESULTS: We have developed a novel optimization framework for identifying regulation in a genetic network using the S-system modeling formalism. We show that balance equations on both mRNA and protein species led to a formulation suitable for analyzing DNA-microarray data whereby protein concentrations have been eliminated and only mRNA relative concentrations are retained. Using this formulation, we examined if it is possible to infer a set of possible genetic regulatory networks consistent with observed mRNA expression patterns. Two origins of changes in mRNA expression patterns were considered. One derives from changes in the biophysical properties of the system that alter the molecular-interaction kinetics and/or message stability. The second is due to gene knock-outs. We reduced the identification problem to an optimization problem (of the so-called mixed-integer non-linear programming class) and we developed an algorithmic procedure for solving this optimization problem. Using simulated data generated by our mathematical model, we show that our method can actually find the regulatory network from which the data were generated. We also show that the number of possible alternate genetic regulatory networks depends on the size of the dataset (i.e. number of experiments), but this dependence is different for each of the two types of problems considered, and that a unique solution requires fewer datasets than previously estimated in the literature. This is the first method that also allows the identification of every possible regulatory network that could explain the data, when the number of experiments does not allow identification of unique regulatory structure.