Effect of the season on the free phytoprostanes content in Cornicabra extra virgin olive oil from deficit irrigated olive trees

BACKGROUND: The effect of regulated deficit irrigation (RDI) on the phytoprostane (PhytoP) content in extra virgin olive (Olea europaea L., cv. Cornicabra) oil (EVOO) was studied. During the 2012 and 2013 seasons, T0 plants were irrigated at 100% ETc, while T1 and T2 plants were irrigated avoiding water deficit during phases I and III of fruit growth and saving water during the non-critical phenological period of pit hardening (phase II), developing amore severewater deficit in T2 plants. In 2013, a fourth treatment (T3) was also performed, which was similar to T2 except that water saving was from the beginning of phase II to 15 days after the end of phase II. RESULTS: 9-F1t-PhytoP, 9-epi-9-F1t-PhytoP, 9-epi-9-D1t-PhytoP, 9-D1t-PhytoP, 16-B1-PhytoP and 9-L1-PhytoP were present in Cornicabra EVOO, and their contents increased in the EVOO fromRDI plants. CONCLUSION: Deficit irrigation during pit hardening or for a further period of 2 weeks thereafter to increase irrigation water saving is clearly critical for EVOO composition because of the enhancement of free PhytoPs, which have potential beneficial effects on human health. The response of individual free PhytoPs to changes in plant water status was not as perceptible as expected, preventing their use as biomarkers of water stress.

Serial microanalysis of renal transcriptomes

Large-scale gene expression studies can now be routinely performed on macroamounts of cells, but it is unclear to which extent current methods are valuable for analyzing complex tissues. In the present study, we used the method of serial analysis of gene expression (SAGE) for quantitative mRNA profiling in the mouse kidney. We first performed SAGE at the whole-kidney level by sequencing 12,000 mRNA tags. Most abundant tags corresponded to transcripts widely distributed or enriched in the predominant kidney epithelial cells (proximal tubular cells), whereas transcripts specific for minor cell types were barely evidenced. To better explore such cells, we set up a SAGE adaptation for downsized extracts, enabling a 1,000-fold reduction of the amount of starting material. The potential of this approach was evaluated by studying gene expression in microdissected kidney tubules (50,000 cells). Specific gene expression profiles were obtained, and known markers (e.g., uromodulin in the thick ascending limb of Henle's loop and aquaporin-2 in the collecting duct) were found appropriately enriched. In addition, several enriched tags had no databank match, suggesting that they correspond to unknown or poorly characterized transcripts with specific tissue distribution. It is concluded that SAGE adaptation for downsized extracts makes possible large-scale quantitative gene expression measurements in small biological samples and will help to study the tissue expression and function of genes not evidenced with other high-throughput methods.

Double-level “orthogonal” dynamic combinatorial libraries on transition metal template

Dynamic combinatorial libraries are mixtures of compounds that exist in a dynamic equilibrium and can be driven to compositional self adaptation via selective binding of a specific assembly of certain components to a molecular target. We present here an extension of this initial concept to dynamic libraries that consists of two levels, the first formed by the coordination of terpyridine-based ligands to the transition metal template, and the second, by the imine formation with the aldehyde substituents on the terpyridine moieties. Dialdehyde 7 has been synthesized, converted into a variety of ligands, oxime ethers L11–L33 and acyl hydrazones L44–L77, and subsequently into corresponding cobalt complexes. A typical complex, Co(L22)22+ is shown to engage in rapid exchange with a competing ligand L11 and with another complex, Co(L22)22+ in 30% acetonitrile/water at pH 7.0 and 25°C. The exchange in the corresponding Co(III) complexes is shown to be much slower. Imine exchange in the acyl hydrazone complexes (L44–L77) is strongly controlled by pH and temperature. The two types of exchange, ligand and imine, can thus be used as independent equilibrium processes controlled by different types of external intervention, i.e., via oxidation/reduction of the metal template and/or change in the pH/temperature of the medium. The resulting double-level dynamic libraries are therefore named orthogonal, in similarity with the orthogonal protecting groups in organic synthesis. Sample libraries of this type have been synthesized and showed the complete expected set of components in electrospray ionization MS.

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to βadrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein–kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein–kinin system could be involved in the development or progression of cardiovascular diseases.

Telomerase inhibitors based on quadruplex ligands selected by a fluorescence assay

The reactivation of telomerase activity in most cancer cells supports the concept that telomerase is a relevant target in oncology, and telomerase inhibitors have been proposed as new potential anticancer agents. The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit telomerase activity. We used a fluorescence assay to identify molecules that stabilize G-quadruplexes. Intramolecular folding of an oligonucleotide with four repeats of the human telomeric sequence into a G-quadruplex structure led to fluorescence excitation energy transfer between a donor (fluorescein) and an acceptor (tetramethylrhodamine) covalently attached to the 5′ and 3′ ends of the oligonucleotide, respectively. The melting of the G-quadruplex was monitored in the presence of putative G-quadruplex-binding molecules by measuring the fluorescence emission of the donor. A series of compounds (pentacyclic crescent-shaped dibenzophenanthroline derivatives) was shown to increase the melting temperature of the G-quadruplex by 2–20°C at 1 μM dye concentration. This increase in Tm value was well correlated with an increase in the efficiency of telomerase inhibition in vitro. The best telomerase inhibitor showed an IC50 value of 28 nM in a standard telomerase repeat amplification protocol assay. Fluorescence energy transfer can thus be used to reveal the formation of four-stranded DNA structures, and its stabilization by quadruplex-binding agents, in an effort to discover new potent telomerase inhibitors.

Letter from Thomas Giraud to William Tudor,

One letter mentioning the French ambassador to Naples, Charles Jean-Marie Alquier. In French.

Estimates of pandemic influenza vaccine effectiveness in Europe, 2009-2010: results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) multicentre case-control study

A multicentre case-control study based on sentinel practitioner surveillance networks from seven European countries was undertaken to estimate the effectiveness of 2009-2010 pandemic and seasonal influenza vaccines against medically attended influenza-like illness (ILI) laboratory-confirmed as pandemic influenza A (H1N1) (pH1N1).

The Impact of Language Opacity and Proficiency on Reading Strategies in Bilinguals: An Eye Movement Study

Reading strategies vary across languages according to orthographic depth - the complexity of the grapheme in relation to phoneme conversion rules - notably at the level of eye movement patterns. We recently demonstrated that a group of early bilinguals, who learned both languages equally under the age of seven, presented a first fixation location (FFL) closer to the beginning of words when reading in German as compared with French. Since German is known to be orthographically more transparent than French, this suggested that different strategies were being engaged depending on the orthographic depth of the used language. Opaque languages induce a global reading strategy, and transparent languages force a local/serial strategy. Thus, pseudo-words were processed using a local strategy in both languages, suggesting that the link between word forms and their lexical representation may also play a role in selecting a specific strategy. In order to test whether corresponding effects appear in late bilinguals with low proficiency in their second language (L2), we present a new study in which we recorded eye movements while two groups of late German-French and French-German bilinguals read aloud isolated French and German words and pseudo-words. Since, a transparent reading strategy is local and serial, with a high number of fixations per stimuli, and the level of the bilingual participants' L2 is low, the impact of language opacity should be observed in L1. We therefore predicted a global reading strategy if the bilinguals' L1 was French (FFL close to the middle of the stimuli with fewer fixations per stimuli) and a local and serial reading strategy if it was German. Thus, the L2 of each group, as well as pseudo-words, should also require a local and serial reading strategy. Our results confirmed these hypotheses, suggesting that global word processing is only achieved by bilinguals with an opaque L1 when reading in an opaque language; the low level in the L2 gives way to a local and serial reading strategy. These findings stress the fact that reading behavior is influenced not only by the linguistic mode but also by top-down factors, such as readers' proficiency.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.