Monitoring Cognitive and Emotional Processes Through Pupil and Cardiac Response During Dynamic Versus Logical Task

The paper deals with the links between physiological measurements and cognitive and emotional functioning. As long as the operator is a key agent in charge of complex systems, the definition of metrics able to predict his performance is a great challenge. The measurement of the physiological state is a very promising way but a very acute comprehension is required; in particular few studies compare autonomous nervous system reactivity according to specific cognitive processes during task performance and task related psychological stress is often ignored. We compared physiological parameters recorded on 24 healthy subjects facing two neuropsychological tasks: a dynamic task that require problem solving in a world that continually evolves over time and a logical task representative of cognitive processes performed by operators facing everyday problem solving. Results showed that the mean pupil diameter change was higher during the dynamic task; conversely, the heart rate was more elevated during the logical task. Finally, the systolic blood pressure seemed to be strongly sensitive to psychological stress. A better taking into account of the precise influence of a given cognitive activity and both workload and related task-induced psychological stress during task performance is a promising way to better monitor operators in complex working situations to detect mental overload or pejorative stress factor of error.     

The effects of acute changes in temperature and oxygen availability on cardiac performance in winter flounder (Pseudopleuronectes americanus)

Studies on how flatfish cardiovascular function responds to environmental challenges are limited, and have largely relied upon indirect methodologies (i.e. Fick principle). Thus, we measured dorsal aortic blood pressure (P_DA) and cardiac function in 8 and 15 °C-acclimated flounder exposed to graded hypoxia, and in 8 °C-acclimated fish exposed to an acute temperature increase to their critical thermal maximum (CTM). The extent of bradycardia in 8 °C-acclimated fish (decrease in heart rate of 41%) was consistent with that observed for other teleosts, as was this species' CTM (25.8 ± 0.5 °C) and its cardiac response to increasing temperature. However, this study provides further examples of how cardiovascular function is controlled differently in the flounder as compared with other fishes. First, the onset of bradycardia in 8 °C-acclimated fish occurred earlier than expected for this inactive and hypoxia-tolerant species (60% water air saturation). Second, resting cardiac output was similar in flounder acclimated to 8 and 15 °C (～ 15 mL min^? 1 kg^? 1), and hypoxic bradycardia was surprisingly absent at 15 °C. Finally, systemic vascular resistance decreased when flounder were exposed to elevated temperature, and this resulted in a 26% fall in P_DA. These are novel findings, however, the extent to which the flounder's behaviour influenced some of the results is unclear.     

Effect of intensive catchment and in-lake restoration procedures on phosphorus concentrations in a eutrophic lake

Lake Okaro is a small, warm monomictic lake in central North Island, New Zealand, which progressed from oligotrophic to eutrophic through the 1960s. Trends in phosphorus (P) concentrations in the lake are linked to multiple restoration efforts over a 5-year period (2003–2008). The restoration procedures include a 2.3 ha constructed wetland established in February 2006 and riparian margin protection to reduce external loading, as well as an Alum application in December 2003 and sediment capping using modified zeolite in September 2008 to reduce internal loading. The annual average total phosphorus (TP) concentration in the lake decreased by 41% from 2004–2005 to 2007–2008. Two predictive models based on external P loading data generally underestimated the measured TP concentrations in the water column due to internal P loading. The relatively rapid response of TP concentrations after reduction of the internal loading using modified zeolite suggests that this technique can effect a rapid decrease in lake water TP concentrations though the trophic state of Lake Okaro showed high resilience to the reduced P loading. It is concluded that the combined effect of all restoration procedures resulted in a relatively rapid decrease in TP concentrations in Lake Okaro, which may be prolonged by continued external load reduction.     

Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I–XV

A series of polyphenolic derivatives, including resveratrol, dobutamine, curcumin, catechin and silymarine were investigated for the inhibition of all the catalytically active mammalian isozymes of the metalloprotein carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I–CA XV. These polyphenols effectively inhibited CAs, with K_Is in the range of 380 nM–12.02 μM. The various isozymes showed quite diverse inhibition profiles with these compounds, which possess scaffolds not present in other investigated CA inhibitors (CAIs). These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors, based on such less investigated scaffolds.     

Discovery of a novel series of potent S1P1 agonists

The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.     

Design and optimization of new piperidines as renin inhibitors

The discovery of a new series of piperidine-based renin inhibitors is described herein. SAR optimization upon the P3 renin sub-pocket is described, leading to the discovery of 9 and 41, two bioavailable renin inhibitors orally active at low doses in a transgenic rat model of hypertension.     

Fast and automated functional classification with MED‐SuMo: An application on purine‐binding proteins

Ligand–protein interactions are essential for biological processes, and precise characterization of protein binding sites is crucial to understand protein functions. MED‐SuMo is a powerful technology to localize similar local regions on protein surfaces. Its heuristic is based on a 3D representation of macromolecules using specific surface chemical features associating chemical characteristics with geometrical properties. MED‐SMA is an automated and fast method to classify binding sites. It is based on MED‐SuMo technology, which builds a similarity graph, and it uses the Markov Clustering algorithm. Purine binding sites are well studied as drug targets. Here, purine binding sites of the Protein DataBank (PDB) are classified. Proteins potentially inhibited or activated through the same mechanism are gathered. Results are analyzed according to PROSITE annotations and to carefully refined functional annotations extracted from the PDB. As expected, binding sites associated with related mechanisms are gathered, for example, the Small GTPases. Nevertheless, protein kinases from different Kinome families are also found together, for example, Aurora‐A and CDK2 proteins which are inhibited by the same drugs. Representative examples of different clusters are presented. The effectiveness of the MED‐SMA approach is demonstrated as it gathers binding sites of proteins with similar structure‐activity relationships. Moreover, an efficient new protocol associates structures absent of cocrystallized ligands to the purine clusters enabling those structures to be associated with a specific binding mechanism. Applications of this classification by binding mode similarity include target‐based drug design and prediction of cross‐reactivity and therefore potential toxic side effects.     

GC/MS based identification of skunk spray maliciously deployed as “biological weapon” to harm civilians

Our laboratory has been asked to elucidate the origin of a strong “toxic smell” present in a prominent politician's office, private house and motorcar. This stinky and pungent atmosphere has caused serious nausea and vomiting to several individuals. Urine samples were collected from the persons presenting symptoms of nausea for toxicological analysis. Drops, paper and cotton swabs of an oily liquid found at the implicated places were submitted by police to our laboratory for investigation. Methanol extracts of the drops were acetylated for gas chromatography/mass spectrometry (GC/MS) analysis in the electron impact mode; the cotton and paper swabs were analysed using headspace-gas chromatography/mass spectrometry (HS-GC/MS). The GC/MS analysis of the acetylated methanol extracts revealed that the major peaks of the chromatogram could be attributed to 2-methylquinoline, to 2-quinolinemethanethiol, to S-2-quinolinemethyl thioacetate, to 2-phenylethanethiol, to bis(E)-2-butenyl disulphide and to bis(3-methylbutyl) disulphide. Several volatile sulphur-containing compounds have been identified with the HS-GC/MS system. Detailed examination of the spectra as well as GC/MS analysis of commercially available skunk secret allowed us to relate the identified compounds to those present in the defence spray of skunks. No health sequels were observed for any of the persons implicated in this case.     

Acute metal stress in Populus tremula×P. alba (717‐1B4 genotype): Leaf and cambial proteome changes induced by cadmium2+

The comprehension of metal homeostasis in plants requires the identification of molecular markers linked to stress tolerance. Proteomic changes in leaves and cambial zone of Populus tremula×P. alba (717‐1B4 genotype) were analyzed after 61 days of exposure to cadmium (Cd) 360 mg/kg soil dry weight in pot‐soil cultures. The treatment led to an acute Cd stress with a reduction of growth and photosynthesis. Cd stress induced changes in the display of 120 spots for leaf tissue and 153 spots for the cambial zone. It involved a reduced photosynthesis, resulting in a profound reorganisation of carbon and carbohydrate metabolisms in both tissues. Cambial cells underwent stress from the Cd actually present inside the tissue but also a deprivation of photosynthates caused by leaf stress. An important tissue specificity of the response was observed, according to the differences in cell structures and functions.