Prebiotic synthesis of sequential peptides on the Hadean beach by a molecular engine working with nitrogen oxides as energy sources

Addressing the still open question of the prebiotic origin of sequential macromolecules (peptides, nucleic acids) on the primitive Earth, we describe a molecular engine (the primary pump), which works at ambient temperature and continuously generates, elongates and complexifies sequential peptides. This new scenario is based on a cyclic reaction sequence, whose keystep is the activation of amino acids into their N‐carboxyanhydrides (NCA) through nitrosation by NOx. This process could have taken place on tidal beaches; it requires a buffered ocean, emerged land and a nitrosating atmosphere. With the help of geochemical studies and computer simulations of atmosphere photochemistry, we show that the primitive Earth during the Hadean may have satisfied all these requirements. © 2001 Society of Chemical Industry.     

Generalized Post Embedding Problems

The Regular Post Embedding Problem extended with partial (co)directness is shown decidable. This extends to universal and/or counting versions. It is also shown that combining directness and codirectness in Post Embedding problems leads to undecidability.     

A note about the complexity of minimizing Nesterov's smooth Chebyshev–Rosenbrock function

This short note considers and resolves the apparent contradiction between known worst-case complexity results for first- and second-order methods for solving unconstrained smooth nonconvex optimization problems and a recent note by Jarre [On Nesterov's smooth Chebyshev–Rosenbrock function, Optim. Methods Softw. (2011)] implying a very large lower bound on the number of iterations required to reach the solution's neighbourhood for a specific problem with variable dimension.     

The MORPHEUS Heterogeneous Dynamically Reconfigurable Platform

Reconfigurable computing offers a wide range of low cost and efficient solutions for embedded systems. The proper choice of the reconfigurable device, the granularity of its processing elements and its memory architecture highly depend on the type of application and their data flow. Existing solutions either offer fine grain FPGAs, which rely on a hardware synthesis flow and offer the maximum degree of flexibility, or coarser grain solutions, which are usually more suitable for a particular type of data flow and applications. In this paper, we present the MORPHEUS architecture, a versatile reconfigurable heterogeneous System-on-Chip targeting streaming applications. The presented architecture exploits different reconfigurable technologies at several computation granularities that efficiently address the different applications needs. In order to efficiently exploit the presented architecture, we implemented a complete software solution to map C applications to the reconfigurable architecture. In this paper, we describe the complete toolset and provide concrete use cases of the architecture.     

Phylogeny of trichomonads based on partial sequences of large subunit rRNA and on cladistic analysis of morphological data

Several domains of large subunit rRNA from nine trichomonad species have been sequenced. Molecular phylogenies obtained with parsimony and distance methods demonstrate the trichomonads are a monophyletic group which branches very early in the eukaryotic tree. The topology of the trees is in general agreement with traditional views on evolutionary and systematic relationships of trichomonads. A clear dichotomy is noted between the subfamily Trichomonadinae and the subfamily Tritrichomonadinae. In the latter subfamily, a second division separates the "Tritrichomonas muris-type" species from the "Tritrichomonas augusta-type" ones. Previous evolutionary schemes in which the Monocercomonadidae were regarded as the most "primitive" and the Trichomonadidae as more "evolved" are not in agreement with our molecular data. The emergence of Monocercomonas and Hypotrichomonas at the base of the Tritrichomonas lineage suggests a secondary loss of some cytoskeletal structures, the costa and undulating membrane in these genera. This is corroborated by the early branching position of Trichomitus, which possesses a costa and an undulating membrane and has usually been placed among the Trichomonadidae on the basis of cytological characters. A cladistic analysis was applied to the available morphological characters in order to produce a hierarchical grouping of the taxa reflecting their morphological diversity.     

Multiplexed-Based Assessment of DNA Damage Response to Chemotherapies Using Cell Imaging Cytometry

The current methods for measuring the DNA damage response (DDR) are relatively labor-intensive and usually based on Western blotting, flow cytometry, and/or confocal immunofluorescence analyses. They require many cells and are often limited to the assessment of a single or few proteins. Here, we used the Celigo^® image cytometer to evaluate the cell response to DNA-damaging agents based on a panel of biomarkers associated with the main DDR signaling pathways. We investigated the cytostatic or/and the cytotoxic effects of these drugs using simultaneous propidium iodide and calcein-AM staining. We also describe new dedicated multiplexed protocols to investigate the qualitative (phosphorylation) or the quantitative changes of eleven DDR markers (H2AX, DNA-PKcs, ATR, ATM, CHK1, CHK2, 53BP1, NBS1, RAD51, P53, P21). The results of our study clearly show the advantage of using this methodology because the multiplexed-based evaluation of these markers can be performed in a single experiment using the standard 384-well plate format. The analyses of multiple DDR markers together with the cell cycle status provide valuable insights into the mechanism of action of investigational drugs that induce DNA damage in a time- and cost-effective manner due to the low amounts of antibodies and reagents required.     

An Overview of the Latest Metabolomics Studies on Atopic Eczema with New Directions for Study

Atopic eczema (AE) is an inflammatory skin disorder affecting approximately 20% of children worldwide and early onset can lead to asthma and allergies. Currently, the mechanisms of the disease are not fully understood. Metabolomics, the analysis of small molecules in the skin produced by the host and microbes, opens a window to observe the mechanisms of the disease which then may lead to new drug targets for AE treatment. Here, we review the latest advances in AE metabolomics, highlighting both the lipid and non-lipid molecules, along with reviewing the metabolites currently known to reside in the skin.     

Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC₅₀) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.