Iron Deprivation in Synechocystis : Inference of Pathways, Non-coding RNAs, and Regulatory Elements from Comprehensive Expression Profiling

Iron is an essential cofactor in many metabolic reactions. Mechanisms controlling iron homeostasis need to respond rapidly to changes in extracellular conditions, but they must also keep the concentration of intracellular iron under strict control to avoid the generation of damaging reactive oxygen species. Due to its role as a redox carrier in photosynthesis, the iron quota in cyanobacteria is about 10 times higher than in model enterobacteria. The molecular details of how such a high quota is regulated are obscure. Here we present experiments that shed light on the iron regulatory system in cyanobacteria. We measured time-resolved changes in gene expression after iron depletion in the cyanobacterium Synechocystis sp. PCC 6803 using a comprehensive microarray platform, monitoring both protein-coding and non-coding transcripts. In total, less than a fifth of all protein-coding genes were differentially expressed during the first 72 hr. Many of these proteins are associated with iron transport, photosynthesis, or ATP synthesis. Comparing our data with three previous studies, we identified a core set of 28 genes involved in iron stress response. Among them were genes important for assimilation of inorganic carbon, suggesting a link between the carbon and iron regulatory networks. Nine of the 28 genes have unknown functions and constitute key targets for further functional analysis. Statistical and clustering analyses identified 10 small RNAs, 62 antisense RNAs, four 59UTRs, and seven intragenic elements as potential novel components of the iron regulatory network in Synechocystis. Hence, our genome-wide expression profiling indicates an unprecedented complexity in the iron regulatory network of cyanobacteria.Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/BIA-MIC/101036/2008]; Deutsche Forschungsgemeinschaft (DFG) Focus program "Sensory and regulatory RNAs in Prokaryotes [SPP1258]; FCT [PEst-OE/EQB/LA0023/2011]info:eu-repo/semantics/publishedVersio

Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

High School Exit Examinations: When Do Learning Effects Generalize?

This paper reviews international and domestic evidence on the effects of three types of high school exit exam systems: voluntary curriculum-based external exit exams, universal curriculum-based external exit exam systems and minimum competency tests that must be passed to receive a regular high school diploma. The nations and provinces that use Universal CBEEES (and typically teacher grades as well) to signal student achievement have significantly higher achievement levels and smaller differentials by family background than otherwise comparable jurisdictions that base high stakes decisions on voluntary college admissions tests and/or teacher grades. The introduction of Universal CBEEES in New York and North Carolina during the 1990s was associated with large increases in math achievement on NAEP tests. Research on MCTs and high school accountability tests is less conclusive because these systems are new and have only been implemented in one country. Cross-section studies using a comprehensive set of controls for family background have not found that students in MCT states score higher on audit tests like the NAEP that carry no stakes for the test taker. The analysis reported in table 1 tells us that the five states that introduced MCTs during the 1990s had significantly larger improvements on NAEP tests than states that made no change in their student accountability regime. The gains, however, are smaller than for the states introducing Universal CBEEES. New York and North Carolina. The most positive finding about MCTs is that students in MCT states earn significantly more during the first eight years after graduation than comparable students in other states suggesting that MCTs improve employer perceptions of the quality of the recent graduates of local high schools

Verified and potential pathogens of predatory mites (Acari: Phytoseiidae)

Several species of phytoseiid mites (Acari: Phytoseiidae), including species of the genera Amblyseius, Galendromus, Metaseiulus, Neoseiulus, Phytoseiulus and Typhlodromus, are currently reared for biological control of various crop pests and/or as model organisms for the study of predator¿prey interactions. Pathogen-free phytoseiid mites are important to obtain high efficacy in biological pest control and to get reliable data in mite research, as pathogens may affect the performance of their host or alter their reproduction and behaviour. Potential and verified pathogens have been reported for phytoseiid mites during the past 25 years. The present review provides an overview, including potential pathogens with unknown host effects (17 reports), endosymbiotic Wolbachia (seven reports), other bacteria (including Cardinium and Spiroplasma) (four reports), cases of unidentified diseases (three reports) and cases of verified pathogens (six reports). From the latter group four reports refer to Microsporidia, one to a fungus and one to a bacterium. Only five entities have been studied in detail, including Wolbachia infecting seven predatory mite species, other endosymbiotic bacteria infecting Metaseiulus (Galendromus, Typhlodromus) occidentalis (Nesbitt), the bacterium Acaricomes phytoseiuli infecting Phytoseiulus persimilis Athias-Henriot, the microsporidium Microsporidium phytoseiuli infecting P. persimilis and the microsporidium Oligosproridium occidentalis infecting M. occidentalis. In four cases (Wolbachia, A. phytoseiuli, M. phytoseiuli and O. occidentalis) an infection may be connected with fitness costs of the host. Moreover, infection is not always readily visible as no obvious gross symptoms are present. Monitoring of these entities on a routine and continuous basis should therefore get more attention, especially in commercial mass-production. Special attention should be paid to field-collected mites before introduction into the laboratory or mass rearing, and to mites that are exchanged among rearing facilities. However, at present general pathogen monitoring is not yet practical as effects of many entities are unknown. More research effort is needed concerning verified and potential pathogens of commercially reared arthropods and those used as model organisms in research

Blood Substitutes in Cardiac Surgery

A safe, inexpensive, noninfectious substitute for red blood cells has long been sought. Despite tremendous advances in blood banking, the logistics of collecting, transporting, and storing human red blood cells contin ues to create infection and shortage problems. The two basic types of blood substitutes currently under devel opment are hemoglobin based and fluorocarbon based. Although they each transport oxygen differently, the basic advantages and limitations are the same. Blood substitute advantages include the unique capacity for room temperature storage, noninfectivity, adequate supply, and low toxicity. Restrictions include limited dosing in the acute period, limited intravascular half-life and, for the fluorocarbons, a requirement for a high PaO2. In addition, there remain questions about the relationship of nitric oxide metabolism to hypertension in hemoglobin solutions. Early clinical and laboratory trials have shown that both types of solutions are effective oxygen-delivery agents, with acceptable side- effect profiles. Clinical trials are currently underway to determine the safety and efficacy of these solutions in patients undergoing cardiopulmonary bypass.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68576/2/10.1177_108925329800200403.pd

An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis

Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.Comment: 54 pages (19 pages main text; 11 Figures; 26 pages of supplementary information). Revised after critical reviews. Accepted for Publication in PLoS ON

Revisiting consistency with random utility maximisation: theory and implications for practical work

While the paradigm of utility maximisation has formed the basis of the majority of applications in discrete choice modelling for over 40 years, its core assumptions have been questioned by work in both behavioural economics and mathematical psychology as well as more recently by developments in the RUM-oriented choice modelling community. This paper reviews the basic properties with a view to explaining the historical pre-eminence of utility maximisation and addresses the question of what departures from the paradigm may be necessary or wise in order to accommodate richer behavioural patterns. We find that many, though not all, of the behavioural traits discussed in the literature can be approximated sufficiently closely by a random utility framework, allowing analysts to retain the many advantages that such an approach possesses

Numerical Simulation of a Passive Control of the Flow Around an Aerofoil Using a Flexible, Self Adaptive Flaplet

© 2018 The Author(s) Self-activated feathers are used by almost all birds to adapt their wing characteristics to delay stall or to moderate its adverse effects (e.g., during landing or sudden increase in angle of attack due to gusts). Some of the feathers are believed to pop up as a consequence of flow separation and to interact with the flow and produce beneficial modifications of the unsteady vorticity field. The use of self adaptive flaplets in aircrafts, inspired by birds feathers, requires the understanding of the physical mechanisms leading to the mentioned aerodynamic benefits and the determination of the characteristics of optimal flaps including their size, positioning and ideal fabrication material. In this framework, this numerical study is divided in two parts. Firstly, in a simplified scenario, we determine the main characteristics that render a flap mounted on an aerofoil at high angle of attack able to deliver increased lift and improved aerodynamic efficiency, by varying its length, position and its natural frequency. Later on, a detailed direct numerical simulation analysis is used to understand the origin of the aerodynamic benefits introduced by the flaplet movement induced by the interaction with the flow field. The parametric study that has been carried out, reveals that an optimal flap can deliver a mean lift increase of about 20% on a NACA0020 aerofoil at an incidence of 20 o degrees. The results obtained from the direct numerical simulation of the flow field around the aerofoil equipped with the optimal flap at a chord Reynolds number of 2 × 10 4 shows that the flaplet movement is mainly induced by a cyclic passage of a large recirculation bubble on the aerofoil suction side. In turns, when the flap is pushed downward, the induced plane jet displaces the trailing edge vortices further downstream, away from the wing, moderating the downforce generated by those vortices and regularising the shedding cycle that appears to be much more organised when the optimal flaplet configuration is selected

Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al