Simulations of UV–visible spectra for analytical applications: phenothiazines as a case study

Simulation of UV–vis spectra over the whole absorption window requires not only an accurate approach for the estimation of electronic transitions' energies, but also to take properly into account solvent and band-broadening effects. Although the first, solvent, can be easily introduced in quantum-chemical calculations at both implicit and explicit levels, the second, band broadening, is more troublesome to evaluate. To this end, in this contribution, we propose a protocol aimed to correctly simulate the whole absorption UV–vis spectra of organic molecules based on time-dependent density functional theory, coupled with implicit and explicit solvent models, and on the use of a fitting procedure with respect to the experimental data in order to define the best band broadening. This protocol is applied to the simulation of absorption spectra of 10H-phenothiazine and three related molecules, N,N-diphenylamine, iminodibenzyl and 10H-phenothiazine-5-oxide, which appear as impurities during its industrial synthesis. The obtained results show not only that the main peak positions are reproduced with an error not exceeding 10 nm (in the 200–400 nm range) but also that the overall shape of the UV–vis spectra can be correctly simulated.     

Apolipoprotein E and diets: a case of gene-nutrient interaction?

Apolipoprotein E has key functions in lipoprotein metabolism, and polymorphisms in the apolipoprotein E gene are associated with distinct lipoprotein patterns. The possibility of gene-nutrient interactions for apolipoprotein E has been addressed in many studies. Although results have generally been mixed, the indications for such an interaction have been more common in studies employing a metabolic challenge. Studies directly designed to examine apolipoprotein E gene-nutrient interactions are needed.     

Fouling of gastropods: a role for parasites?

A sample of mud snails Hydrobia ulvae (Prosobranchia) from an intertidal population revealed that the shells of trematode-infected specimens were especially likely to be fouled with epibionts. Experimentally trematode-infected Biomphalaria glabrata (Pulmonata) appeared to be especially prone to develop epigrowth in comparison with uninfected conspecifics as well. These findings suggest an interaction between trematode infections and epibiosis in aquatic gastropods. The two most likely explanations for this are (1) that trematode infections weakens the snails' natural defences against epibionts, or (2) that the defences against epibionts also are effective against invading trematodes, causing snail specimens with a particularly good fouling defence to be less likely to become infected.     

Is research effort allocated efficiently for conservation? Felidae as a global case study

Some species face greater anthropogenic threats than others, and have increased need for scarce conservation resources. Yet how resources are allocated for conservation remains little known. I examined the distribution of research effort, an index of resource allocation, across Felidae (the cat family), a diverse, widely-distributed, and threatened taxon. I performed complete searches of the published literature for all cat species from 1986 to 2007, collecting a total of 2,462 papers, of which 926 represented in situ studies. Threat status, as ranked by a World Conservation Union report in 1996, was significantly correlated with geographical range size, with narrowly distributed species tending to be more at risk. Unlike in many other taxa, threat status was not correlated with body size. The number of total and in situ publications (“research effort”) per species was significantly and positively related to body size, but not to threat status or geographical range size. Research effort, rather than being distributed according to actual threat status, is highly skewed towards large species. However, the ratio of the number of studies on the 10 smallest cat species to the number on the 10 largest species has increased significantly since 1986. Yet many species remain severely understudied; I identify 14 cat species that are threatened and have <10 in situ publications each. These species critically require a greater share of the conservation research effort.     

Abundance–suitability relationships for invasive species: Epiphyas postvittana as a case study

Biological Invasions - Prediction of the geographic distribution of an exotic species in a new environment is an important element of risk assessment as it provides an assessment of the spatial...     

A new case for a presynaptic role of dendrites: An immunocytochemical study of the N. Raphé Dorsalis

The distribution of serotonin (5-HT) was determined by the application of the prembedding peroxidase-anti-peroxidase (PAP) technique in vibratome and ultrathin sections of the brain stem. The antiserum stained the neuronal groups B₁ to B₉. Somata, dendrites and axons of multipolar and bipolar neurons were recognized in the usual locations. The most commonly found profiles in the area of the n.raphe dorsalis were dendrites. The search for axon terminals was unsuccesful. The labeled dendrites appear in synaptic contact with unlabeled endings containing round or pleomorphic vesicles, and occasionally some large dense core vesicles. Contacts between two labeled dendrites or processes were not found. Occasionally a dendrodendritic junction between a 5-HT labeled dendrite and an unlabeled dendrite has been found. There are areas of the dendritic membrane free of synaptic junctions and free of glial insulation. Results are discussed in relation with the previously proposed presynaptic role of the dendrites in the neuronal circuitry of then. raphé dorsalis.Special Issue dedicated to Prof. Eduardo De Robertis.Research supported by grants from the CONICET and SECYT, Argentina.     

Coenzyme Q10: is there a clinical role and a case for measurement?

Coenzyme Q(10) (CoQ(10)) is an essential cofactor in the mitochondrial electron transport pathway, and is also a lipid-soluble antioxidant. It is endogenously synthesised via the mevalonate pathway, and some is obtained from the diet. CoQ(10) supplements are available over the counter from health food shops and pharmacies. CoQ(10) deficiency has been implicated in several clinical disorders, including but not confined to heart failure, hypertension, Parkinson's disease and malignancy. Statin, 3-hydroxy-3- methyl-glutaryl (HMG)-CoA reductase inhibitor therapy inhibits conversion of HMG-CoA to mevalonate and lowers plasma CoQ(10) concentrations. The case for measurement of plasma CoQ(10) is based on the relationship between levels and outcomes, as in chronic heart failure, where it may identify individuals most likely to benefit from supplementation therapy. During CoQ(10) supplementation plasma CoQ(10) levels should be monitored to ensure efficacy, given that there is variable bioavailability between commercial formulations, and known inter-individual variation in CoQ(10) absorption. Knowledge of biological variation and reference change values is important to determine whether a significant change in plasma CoQ(10) has occurred, whether a reduction for example following statin therapy or an increase following supplementation. Emerging evidence will determine whether CoQ(10) does indeed have an important clinical role and in particular, whether there is a case for measurement.     

Are aggregation-fisheries sustainable? Reef fish fisheries as a case study

Reef fish spawning aggregations are attractive and often lucrative to fish but particularly vulnerable to fishing, with many cases of declines or extirpations. While awareness of the risks of aggregation exploitation has grown substantially in the tropical western Atlantic in the last decade, the phenomenon of aggregation-spawning is little known in the vast Indo-Pacific region where few aggregations are managed or monitored, and are rarely considered in marine-protected area designations. Even in the tropical western Atlantic and Caribbean, marine-protected area planning, until recently, did not typically consider spawning aggregations. Available data and analyses of aggregation-fisheries and aggregating species strongly suggest that: (1) the majority of known aggregations that are exploited are yielding declining landings; (2) aggregating species show greatest overall declines in local fisheries when their aggregations are also exploited; (3) from an economic perspective, aggregation fishing may yield lower prices for fish, or aggregations may be more valuable unexploited, as a source of fish for local fisheries or as tourist attractions; (4) hyperstability can mask declines in aggregation-fisheries, based on fishery-dependent data; (5) monitoring of aggregation catches by either fishery-dependent or fishery-independent means is deceptively challenging. There are also possible ecosystem-level consequences of reducing or eliminating spawning aggregations. We conclude that aggregation-fisheries are likely to be sustainable only for limited subsistence-level use, that the precautionary principle should be more widely applied in aggregation-fisheries and that, despite growing interest in aggregations over the last decade, few of the key biological questions necessary for effective management have been, or are being, addressed.     

In silico binding free energy predictability with π-π interaction energy-augmented scoring function: benzimidazole Raf inhibitors as a case study

The ability to estimate binding affinities of ligands precisely is of paramount importance in designing drugs. Docking programs are used primarily to predict the binding mode of ligands to receptors. However, current scoring functions as used in docking programs are not reliable enough to predict binding affinities of ligands without any further calculations. In the present study, we investigate the usefulness of adding π-π interaction energies between ring groups of residues and ligands to the scoring function for docking. It is found that such addition helps ranking ligand activities more correctly. LMP2 calculation is used to measure π-π interaction energies between ring groups. The result of this simple addition shows possibility of π-π interaction generalization in scoring functions.     

Uracil-amino acid as a scaffold for β-sheet peptidomimetics: Study of photophysics and interaction with BSA protein

We report herein the uracil-di-aza-amino acid (U^rAA) as a new family of molecular scaffold to induce β-hairpin structure with H-bonded β-sheet conformation in a short peptide. This has been demonstrated in two conceptual fluorescent pentapeptides wherein triazolylpyrenyl alanine and/or triazolylmethoxynapthyl alanine (^TPyAla_Do and/or ^TMNapAla_Do) are embedded into two arms of the uracil-amino acid via an intervening leucine. Conformational analysis by CD, IR, variable temperature and 2D NMR spectroscopy reveals the β-hairpin structures for both the peptides. Study of photophysical property reveals that the pentapeptide containing fluorescent triazolyl unnatural amino acids ^TMNapAla_Do and ^TPyAla_Do at the two termini exhibits dual path entry to exciplex emission-either via FRET from ^TMNapAla_Do to ^TPyAla_Do or via direct excitation of a FRET acceptor, ^TPyAla_Do. The other pentapeptide with ^TPyAla_Do/^TPyAla_Do pair shows excimer emission. Furthermore, both the peptides maintaining their fundamental photophysics are found to interact with BSA as only a test biomolecule.     

Tyrosine phosphorylation as a conformational switch: a case study of integrin β3 cytoplasmic tail

Reversible protein phosphorylation is vital for many fundamental cellular processes. The actual impact of adding and removing phosphate group(s) is 3-fold: changes in the local/global geometry, alterations in the electrostatic potential and, as the result of both, modified protein-target interactions. Here we present a comprehensive structural investigation of the effects of phosphorylation on the conformational as well as functional states of a crucial cell surface receptor, α(IIb)β(3) integrin. We have analyzed phosphorylated (Tyr(747) and Tyr(759)) β(3) integrin cytoplasmic tail (CT) primarily by NMR, and our data demonstrate that under both aqueous and membrane-mimetic conditions, phosphorylation causes substantial conformational rearrangements. These changes originate from novel ionic interactions and revised phospholipid binding. Under aqueous conditions, the critical Tyr(747) phosphorylation prevents β(3)CT from binding to its heterodimer partner α(IIb)CT, thus likely maintaining an activated state of the receptor. This conclusion was tested in vivo and confirmed by integrin-dependent endothelial cells adhesion assay. Under membrane-mimetic conditions, phosphorylation results in a modified membrane embedding characterized by significant changes in the secondary structure pattern and the overall fold of β(3)CT. Collectively these data provide unique molecular insights into multiple regulatory roles of phosphorylation.     

Mechanisms of laser nanoparticle-based techniques for gene transfection—a calculation study

Cell plasma membranes can be transiently permeabilized to uptake exogenous molecules with high efficiency using a laser nanoparticle-based gene transfection technique. In combination with experimental results, a theoretical model is set up to calculate the temperature distribution and variance around the nanoparticles. This paper also provides a thorough discussion of the underlying mechanisms of cell permeabilization. We find that, rapid heating of the particles and the accompanying extreme temperature rise can lead to microbubble formation around laser-heated particles, which is the origin of photoacoustic effects and other nonlinear optical responses. This transient heat is also capable of causing protein denaturation through thermal inactivation and photochemistry. Furthermore, the dynamic mode that involves the overlapping of bubbles is presented. This mode can significantly increase the plasma membrane permeability of the cells without affecting their viability.     

Assessment of β-tubulin gene as a complementary molecular marker for desert truffle identification: a study case on Tunisian samples

Tunisian desert truffles have been identified on the basis of the internal transcribed spacer (ITS) locus as Tirmania nivea, Terfezia bouderii and T. arenaria. ITS and, for the first time, β-tubulin gene were employed in the phylogenetic analyses of these species to assess whether β-tubulin gene could be a complementary molecular tool for resolution of phylogenetic species. From their comparison, both markers showed to be suitable to distinguish Tirmania nivea from Terfezia bouderii and T. arenaria and, focusing on the T. boudieri complex, to assign the phylogenetic types previously described. In addition to give a first glimpse into the distribution of desert truffles from north to south of Tunisia, we then suggest to use the β-tubulin gene as a complementary marker to ITS. This indication can be useful above all for the phylogenetic reconstruction of the T. boudieri complex.     

Cortical maps: a role for astrocytes?

Astrocytes are a multifunctional cell type in the nervous system that can influence neurons and synapses in numerous ways. Astrocytes have been suggested to play important roles in synapse formation during development, as well as in multiple forms of synaptic plasticity in the developing and adult brain. Astrocytes respond to nearby neural activity with elevations in cytosolic calcium concentration, and in sensory cortex these calcium responses have been shown to be topographically aligned to neuronal sensory maps. Here, we review recent evidence for astrocyte interactions with neural circuits, with particular emphasis on how these interactions may shape the development, arrangement and plasticity of cortical sensory maps.