Effects on the crank torque profile when changing pedalling cadence in level ground and uphill road cycling

Despite the importance of uphill cycling performance during cycling competitions, there is very little research investigating uphill cycling, particularly concerning field studies. The lack of research is partly due to the difficulties in obtaining data in the field. The aim of this study was to analyse the crank torque in road cycling on level and uphill using different pedalling cadences in the seated position. Seven male cyclists performed four tests in the seated position (1) on level ground at 80 and 100 rpm, and (2) on uphill road cycling (9.25% grade) at 60 and 80 rpm.The cyclists exercised for 1 min at their maximal aerobic power. The bicycle was equipped with the SRM Training System (Schoberer, Germany) for the measurement of power output (W), torque (Nm), pedalling cadence (rpm), and cycling velocity (km h(-1)). The most important finding of this study indicated that at maximal aerobic power the crank torque profile (relationship between torque and crank angle) varied substantially according to the pedalling cadence and with a minor effect according to the terrain. At the same power output and pedalling cadence (80 rpm) the torque at a 45 degrees crank angle tended (p < 0.06) to be higher (+26%) during uphill cycling compared to level cycling. During uphill cycling at 60 rpm the peak torque was increased by 42% compared with level ground cycling at 100 rpm.When the pedalling cadence was modified, most of the variations in the crank torque profile were localised in the power output sector (45 degrees to 135 degrees).     

Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 1

Herein is described a new class of selective sigma1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50 = 16 nM) for the sigma1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher sigma1 affinity (IC50 approximately 1 nM).     

Docking study: PPARs interaction with the selected alternative plasticizers to di(2-ethylhexyl) phthalate

Phthalates, used in medical devices (MDs), have been identified as reproductive and developmental toxicants. Their toxicity varies somewhat depending on the specific phthalate and is in part linked to the activation of Peroxisome Proliferating-Activated Receptors (PPARs). So, the use of MDs containing targeted phthalates such as di(2-ethylhexyl) phthalate (DEHP) has been challenged by European directive 2007/47/EC. Therefore, MDs manufacturers were forced to quickly find replacement plasticizers. However, very little toxicological and epidemiological studies are available on human health. So, we proceeded to dock these chemicals in order to identify compounds that are likely to interact with PPARs binding sites. The results obtained are generally very mixed on the harmlessness of these alternatives. Moreover, no data exist on the biological effects of their possible metabolites. As DEHP toxicity resulted mainly from its major metabolites, generalizing the use of these plasticizers without conducting extensive studies on the possible effects on human health of their metabolites seems inconceivable.     

Insect herbivores should follow plants escaping their relatives

Numerous observational studies have documented conspecific negative density-dependence that is consistent with the Janzen–Connell Hypothesis (JCH) of diversity maintenance. However, there have been few experimental tests of a central prediction of the JCH: that removing host-specific enemies should lead to greater increases in per capita recruitment in areas of higher host density or lower relative phylogenetic diversity. Using spatially randomized plots of high and low host biomass in a temperate grassland biodiversity experiment, we treated developing seedheads of six prairie perennials to factorial applications of fungicide and insecticide. We measured predispersal seed production, seed viability, and seedling biomass. Results were highly species-specific and idiosyncratic. Effects of insect seed predators and fungal pathogens on predispersal responses varied with neither conspecific biomass nor phylogenetic diversity, suggesting that—at least at the predispersal stage and for the insect and fungal seed predators we were able to exclude—the JCH is not sufficient to contribute to negative conspecific density-dependence for these dominant prairie species.     

ESTIMATING THE DURATION OF SPECIATION FROM PHYLOGENIES

Speciation is not instantaneous but takes time. The protracted birth–death diversification model incorporates this fact and predicts the often observed slowdown of lineage accumulation toward the present. The mathematical complexity of the protracted speciation model has barred estimation of its parameters until recently a method to compute the likelihood of phylogenetic branching times under this model was outlined (Lambert et al. 2014 ). Here, we implement this method and study using simulated phylogenies of extant species how well we can estimate the model parameters (rate of initiation of speciation, rate of extinction of incipient and good species, and rate of completion of speciation) as well as the duration of speciation, which is a combination of the aforementioned parameters. We illustrate our approach by applying it to a primate phylogeny. The simulations show that phylogenies often do not contain enough information to provide unbiased estimates of the speciation‐initiation rate and the extinction rate, but the duration of speciation can be estimated without much bias. The estimate of the duration of speciation for the primate clade is consistent with literature estimates. We conclude that phylogenies combined with the protracted speciation model provide a promising way to estimate the duration of speciation.     

Homology modelling of the serotoninergic 5-HT2c receptor

Since its discovery, 5-hydroxytryptamine, more usually called serotonin, has been an elusive candidate as a major mood regulator. This capacity gives it a great importance in the treatment of depression. It is within this framework that our work takes place, as it is related more particularly to a new therapeutic class whose leader is agomelatine. This compound binds to the melatoninergic receptors and to the serotoninergic 5-HT2c receptor, giving rise to the MASSA concept (Melatonin Agonist and Selective Serotonin Antagonist). Like the majority of the serotoninergic receptors, the sub-type 5-HT2c is a G-protein coupled receptor (GPCR). The three-dimensional structure of 5-HT2c is not experimentally known, and we thus resorted to comparative homology modelling to build a model allowing us to study its interactions with agomelatine.     

Isobolographic analysis of the dual-site synergism in the antinociceptive response of tramadol in the formalin test in rats

Tramadol is an atypical opioid with a complex mechanism of action including a synergistic interaction between the parent drug and an active metabolite. The local action of the parent drug is poorly documented. This study was designed to evaluate the site-site interaction of the antinociception produced by tramadol given by two different routes. The effects of individual and fixed-ratio combinations of intraplantar (i.pl.) and intraperitoneal (i.p.) tramadol were evaluated using the formalin test in rats. Isobolographic analysis was employed to identify the synergy produced by combinations. In both first and second phases of the formalin test, tramadol was active not only by the systemic (ED50 10.2+/-2.1 and 7.1+/-0.5 mg/kg i.p.) but also by the local route (ED50 171.0+/-44.8 and 134.6 microg/paw i.pl.). The isobolographic analysis revealed a "self-synergism" in the antinociceptive effect between the two routes of administration, as the experimental ED50 (211.1+/-13.6 and 45.9+/-3.9 "dose units" phase 1 and 2, respectively) of the combination was significantly lower than the theoretical ED50 (422.2+/-50.5 and 138.5+/-9.2 "dose units"). The mechanism underlying this self-synergism appears to be partially opioid since systemic but not local naloxone reversed the potentiation. The observed dual-site interaction in the antinociceptive action of tramadol provides insights for alternatives in the management of pain.     

Synthesis and anticancer activity of analogues of phenstatin,with a phenothiazine A-ring,as a new class of microtubule-targeting agents

A new family of microtubule-targeting agents with a phenothiazine A-ring was synthesized and evaluated for anti-proliferative activity and interaction with tubulin. These new derivatives showed significant activities against cellular proliferation and tubulin polymerization, rather similar to those of phenstatin. Phenothiazine derivative 21 proved to be the most potent compound synthesized with GI₅₀ values ranging from 29 to 93 nM on different cell lines. The same compound showed a better inhibition of COLO 205, A498, and MCF7 cell lines than the parent phenstatin.