Nanomechanical characterization of phospholipid bilayer islands on flat and porous substrates: a force spectroscopy study.

In this study, we compare for the first time the nanomechanical properties of lipid bilayer islands on flat and porous surfaces. 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) bilayers were deposited on flat (silicon and mica) and porous silicon (pSi) substrate surfaces and examined using atomic force spectroscopy and force volume imaging. Force spectroscopy measurements revealed the effects of the underlying substrate and of the lipid phase on the nanomechanical properties of bilayers islands.

[Health information on the Internet and trust marks as quality indicators: vaccines case study].

Objectives: To find out the prevalence of quality trust marks present in websites and to analyse the quality of these websites displaying trust marks compared with those that do not display them, in order to put forward these trust marks as a quality indicator.

Design: Cross-sectional study.

Setting: Internet.

Nosocomial spread of linezolid-resistant Staphylococcus haemolyticus infections in an intensive care unit.

This report documents the nosocomial spread for an 18-month period of a single clone of linezolid- and teicoplanin-resistant Staphylococcus haemolyticus associated primarily with catheter-related bacteremia in intensive care unit patients. All linezolid-resistant isolates had the same G2576T mutation in at least 1 copy of the 23S rRNA gene.

Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands.

A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D(1), D(2), and D(3) receptors. Some of these compounds showed high D(2) and/or D(3) affinity and selectivity over the D(1) receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D(2) and D(3) affinities.

Hsp104 targets multiple intermediates on the amyloid pathway and suppresses the seeding capacity of Abeta fibrils and protofibrils.

The heat shock protein Hsp104 has been reported to possess the ability to modulate protein aggregation and toxicity and to "catalyze" the disaggregation and recovery of protein aggregates, including amyloid fibrils, in yeast, Escherichia coli, mammalian cell cultures, and animal models of Huntington's disease and Parkinson's disease. To provide mechanistic insight into the molecular mechanisms by which Hsp104 modulates aggregation and fibrillogenesis, the effect of Hsp104 on the fibrillogenesis of amyloid beta (Abeta) was investigated by characterizing its ability to interfere with oligomerization and fibrillogenesis of different species along the amyloid-formation pathway of Abeta. To probe the disaggregation activity of Hsp104, its ability to dissociate preformed protofibrillar and fibrillar aggregates of Abeta was assessed in the presence and in the absence of ATP.

Synthesis, binding affinity, and molecular docking analysis of new benzofuranone derivatives as potential antipsychotics.

The complex etiology of schizophrenia has prompted researchers to develop clozapine-related multitarget strategies to combat its symptoms. Here we describe a series of new 6-aminomethylbenzofuranones in an effort to find new chemical structures with balanced affinities for 5-HT2 and dopamine receptors. Through biological and computational studies of 5-HT2A and D2 receptors, we identified the receptor serine residues S3.

Knowledge environments representing molecular entities for the virtual physiological human.

In essence, the virtual physiological human (VPH) is a multiscale representation of human physiology spanning from the molecular level via cellular processes and multicellular organization of tissues to complex organ function. The different scales of the VPH deal with different entities, relationships and processes, and in consequence the models used to describe and simulate biological functions vary significantly. Here, we describe methods and strategies to generate knowledge environments representing molecular entities that can be used for modelling the molecular scale of the VPH.

How changes in the sequence of the peptide CLPFFD-NH2 can modify the conjugation and stability of gold nanoparticles and their affinity for beta-amyloid fibrils.

In a previous work, we studied the interaction of beta-amyloid fibrils (Abeta) with gold nanoparticles (AuNP) conjugated with the peptide CLPFFD-NH2. Here, we studied the effect of changing the residue sequence of the peptide CLPFFD-NH2 on the efficiency of conjugation to AuNP, the stability of the conjugates, and the affinity of the conjugates to the Abeta fibrils. We conjugated the AuNP with CLPFFD-NH 2 isomeric peptides (CDLPFF-NH2 and CLPDFF-NH2) and characterized the resulting conjugates with different techniques including UV-Vis, TEM, EELS, XPS, analysis of amino acids, agarose gel electrophoresis, and CD.

Diastereoselective synthesis of delta-aminoacids through domino Ireland-Claisen rearrangement and Michael addition.

A novel domino reaction--stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition--is described. A protocol starting from Baylis-Hillman adducts 3a-f using chiral lithium amide affords optically active gamma-substituted delta-amino acids 4a-f with high diastereoselectivities and enantioselectivities. The acid can be isolated easily from large-scale reactions and transformed to 2,3-disubstituted piperidines 11 or 2-substituted nipecotic acid derivates 12.

OSIRISv1.2: a named entity recognition system for sequence variants of genes in biomedical literature.

Background: Single Nucleotide Polymorphisms, among other type of sequence variants, constitute key elements in genetic epidemiology and pharmacogenomics. While sequence data about genetic variation is found at databases such as dbSNP, clues about the functional and phenotypic consequences of the variations are generally found in biomedical literature. The identification of the relevant documents and the extraction of the information from them are hampered by the large size of literature databases and the lack of widely accepted standard notation for biomedical entities.

Synthesis, adenosine receptor binding and 3D-QSAR of 4-substituted 2-(2'-furyl)-1,2,4-triazolo[1,5-a]quinoxalines.

A collection of 25 2-(2'-furyl)-1,2,4-triazolo[1,5-a]quinoxalines incorporating different substitution patterns at position 4 have been synthesized and their binding affinity towards human adenosine receptors (hA(1), hA(2A), hA(2B) and hA(3)) was determined. The biological data show that several potent at hA(1), but lightly selective, adenosine ligands were identified. Moreover, these results confirmed the hypothesis that the structural modifications carried out on the 4-position of the tricyclic system produces a remarkable modification of the adenosine receptorial profile.

Mechanical properties of alkanethiol monolayers studied by force spectroscopy.

The mechanical properties of alkanethiol monolayers on Au(111) in KOH solution have been studied by force spectroscopy. The analysis of the vertical force versus penetration curves showed that monolayer penetration is a stepped process that combines elastic regions with sudden penetration events. The structural meaning of these events can be explained both by the creation of gauche defects on the hydrocarbon chains and by a cooperative molecular tilting model proposed by Barrena et al.

1-, 3- and 8-substituted-9-deazaxanthines as potent and selective antagonists at the human A2B adenosine receptor.

A large series of piperazin-, piperidin- and tetrahydroisoquinolinamides of 4-(1,3-dialkyl-9-deazaxanthin-8-yl)phenoxyacetic acid were prepared through conventional or multiple parallel syntheses and evaluated for their binding affinity at the recombinant human adenosine receptors, chiefly at the hA(2B) and hA(2A) receptor subtypes. Several ligands endowed with high binding affinity at hA(2B) receptors, excellent selectivity over hA(2A) and hA(3) and a significant, but lower, selectivity over hA(1) were identified. Among them, piperazinamide derivatives 23 and 52, and piperidinamide derivative 69 proved highly potent at hA(2B) (K(i)=11, 2 and 5.

Identifying gene-specific variations in biomedical text.

The influence of genetic variations on diseases or cellular processes is the main focus of many investigations, and results of biomedical studies are often only accessible through scientific publications. Automatic extraction of this information requires recognition of the gene names and the accompanying allelic variant information. In a previous work, the OSIRIS system for the detection of allelic variation in text based on a query expansion approach was communicated.

[Pneumonia in the elderly population over 70 years with limited functional condition: case-control study of institutionalized patients].

Objective: Community acquired pneumonia (CAP) of the elderly is an increasingly important growing health problem due to its prevalence and mortality. Among the factors that are usually related with poor evolution are advanced age, poor functional status and coming from a socio-health care institution such as residential homes for the elderly. In this study, we have chosen a population over 70 years of age with limited functional capacity (Barthel Index < 50) in order to know if coming from a residential home for the elderly is an isolated factor that is associated to worse prognosis of CAP.

Bacteremia due to clonally derived methicillin-resistant, gentamicin-susceptible isolates and methicillin-susceptible, gentamicin-resistant isolates of Staphylococcus aureus.

We report recurrent bacteremia due to mixed infection with two clonally derived isolates of Staphylococcus aureus in a patient with Sezary syndrome. The two isolates, one gentamicin resistant and methicillin susceptible and the other gentamicin susceptible and methicillin resistant, developed by the deletion of the mecA, ant(4')Ia, and aacA-aphD genes from a common gentamicin-resistant and methicillin-susceptible ancestor.

Synthesis of novel antitumoural analogues of dysidiolide from ent-halimic acid.

Several sesterterpenolides analogues of dysidiolide have been synthesized and their in vitro antitumoural activity against human HeLa, A549, HT-29 and HL-60 carcinoma cells is presented. The proliferation inhibition data showed a significant antitumour activity of the compounds 1b, 2a, 2b, 3a, 3b, 4a, 4b, 5, inhibiting proliferation of distinct cancer cell types with an IC(50) in the low micromolar range.

Thermal response of Langmuir-Blodgett films of dipalmitoylphosphatidylcholine studied by atomic force microscopy and force spectroscopy.

The topographic evolution of supported dipalmitoylphosphatidylcholine (DPPC) monolayers with temperature has been followed by atomic force microscopy in liquid environment, revealing the presence of only one phase transition event at approximately 46 degrees C. This finding is a direct experimental proof that the two phase transitions observed in the corresponding bilayers correspond to the individual phase transition of the two leaflets composing the bilayer. The transition temperature and its dependency on the measuring medium (liquid saline solution or air) is discussed in terms of changes in van der Waals, hydration, and hydrophobic/hydrophilic interactions, and it is directly compared with the transition temperatures observed in the related bilayers under the same experimental conditions.

Multistructure 3D-QSAR studies on a series of conformationally constrained butyrophenones docked into a new homology model of the 5-HT2A receptor.

The present study is part of a long-term research project aiming to gain insight into the mechanism of action of atypical antipsychotics. Here we describe a 3D-QSAR study carried out on a series of butyrophenones with affinity for the serotonin-2A receptor, aligned by docking into the binding site of a receptor model. The series studied has two peculiarities: (i) all the compounds have a chiral center and can be represented by two enantiomeric structures, and (ii) many of the structures can bind the receptor in two alternative orientations, posing the problem of how to select a single representative structure for every compound.

Long persistence of methicillin-susceptible strains of Staphylococcus aureus causing sepsis in a neonatal intensive care unit.

Molecular epidemiology of Staphylococcus aureus strains causing bacteremia in neonates during 2002 to 2005 revealed seven clones, with four MSSA clones responsible for 80% of the cases. Some clones persisted or reappeared throughout the study. Three bacteremic clones were found colonizing health care workers (HCWs), particularly clone C, which was harbored by at least 15% of HCWs.

Ozone in Spain's national parks and protected forests.

In general, it is difficult to measure air pollutant concentrations in remote areas, as they are mostly national parks and protected areas. Passive samplers provide an accurate and inexpensive method for measuring cumulative exposures of different air pollutants. They have been used to collect ozone data in both laboratory and field at different geographical scales.

Atomic force microscopy and force spectroscopy study of Langmuir-Blodgett films formed by heteroacid phospholipids of biological interest.

Langmuir-Blodgett (LB) films of two heteroacid phospholipids of biological interest 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), as well as a mixed monolayer with chi(POPC)=0.4, were transferred onto mica in order to investigate by a combination of atomic force microscopy (AFM) and force spectroscopy (FS) their height, and particularly, their nanomechanical properties. AFM images of such monolayers extracted at 30 mN m(-1) revealed a smooth and defect-free topography except for the POPE monolayer.

PM10 speciation and determination of air quality target levels. A case study in a highly industrialized area of Spain.

The paper shows how PM speciation studies allow the evaluation of the strategies to be followed to diminish PM pollution in highly industrialized areas with a large number of potential pollution sources. Evolution of levels and speciation of PM10 in the ceramic producing area of Castelló (East Spain) was studied from April 2002 until December 2005. PM10 levels were measured at one rural (Borriana-rural), two suburban (Almassora and Onda) and three urban (Borriana-urban, L'Alcora and Vila-real) sites, all influenced by the ceramics industry.