The ambitious role of anti angiogenesis molecules: Turning a cold tumor into a hot one

In renal cancer emerging treatment options are becoming available and there is a strong need to combine therapies to reformulate and adjourn clinical practice. We here highlight and discuss the need to take advantage of the common immune targets to design combined strategies to increase clinical responses

Biological activity of somatostatin receptors in GC rat tumour somatotrophs: evidence with sst1-sst5 receptor-selective nonpeptidyl agonists

The physiological actions of somatostatin-14 (SRIF) receptor subtypes (sst1-sst5), which are endogenously expressed in GC cells, have not yet been elucidated, although there is evidence that sst2 receptors are negatively coupled to cytosolic free Ca2+ concentration ([Ca2+]i) and cAMP accumulation. In addition, both sst1 and sst2 receptors are negatively coupled to growth hormone (GH) secretion in GC cells. Here we report on studies concerning the expression, the pharmacology and the functional role of native SRIF receptors in GC cells with the use of five nonpeptidyl agonists, highly selective for each of the SRIF receptors. Radioligand binding studies show that sst2 and sst5 receptors are present at different relative densities, while the presence of sst3 and sst4 receptors appears to be negligible. The absence of sst1 receptor binding was unexpected in view of sst1 receptor functional effects on GH secretion. This suggests very efficient receptor-effector coupling of a low density population of sst1 receptors. Functionally, only sst2 receptors are coupled to the inhibition of [Ca2+]i and cAMP accumulation and the selective activation of sst5 receptors facilitates the stimulation of adenylyl cyclase activity through Gi/o proteins. This effect was not observed when sst2 and sst5 receptors were simultaneously activated, suggesting that there is a functional interaction between sst2 and sst5 receptors. In addition, sst1, sst2 and sst5 receptor activation inhibits GH release, further indicating that SRIF can modulate GH secretion in GC cells through mechanisms both dependent and independent on [Ca2+]i and cAMP-dependent pathways. The present data suggest SRIF-mediated functional effects in GC cells to be very diverse and provide compelling arguments to propose that multiple native SRIF receptors expressed in the same cells are not simply redundant, but contribute to marked signalling diversity.L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com

Long-Lasting Metabolic Imbalance Related to Obesity Alters Olfactory Tissue Homeostasis and Impairs Olfactory-Driven Behaviors.

Obesity is associated with chronic food intake disorders and binge eating. Food intake relies on the interaction between homeostatic regulation and hedonic signals among which, olfaction is a major sensory determinant. However, its potential modulation at the peripheral level by a chronic energy imbalance associated to obese status remains a matter of debate. We further investigated the olfactory function in a rodent model relevant to the situation encountered in obese humans, where genetic susceptibility is juxtaposed on chronic eating disorders. Using several olfactory-driven tests, we compared the behaviors of obesity-prone Sprague-Dawley rats (OP) fed with a high-fat/high-sugar diet with those of obese-resistant ones fed with normal chow. In OP rats, we reported 1) decreased odor threshold, but 2) poor olfactory performances, associated with learning/memory deficits, 3) decreased influence of fasting, and 4) impaired insulin control on food seeking behavior. Associated with these behavioral modifications, we found a modulation of metabolism-related factors implicated in 1) electrical olfactory signal regulation (insulin receptor), 2) cellular dynamics (glucorticoids receptors, pro- and antiapoptotic factors), and 3) homeostasis of the olfactory mucosa and bulb (monocarboxylate and glucose transporters). Such impairments might participate to the perturbed daily food intake pattern that we observed in obese animals

Hydrophobin: fluorosurfactant-like properties without fluorine

The stabilization of fluorous oil droplets in aqueous environment is a critical issue in the preparation of emulsified systems for biomedical applications and in emulsion polymerization technology, due to the extreme immiscibility of aqueous and fluorous phases. We present here a detailed study on the behavior of the hydrophobin HFBI, i.e. a small natural protein endowed with exceptional surface activity, at the interface between aqueous and fluorous phases. HFBI behaves as an efficient and sustainable surfactant at remarkably low concentrations and forms a strong and elastic film at the interface between the two phases. We also show proof-of-concept experiments on the use of HFBI as a surfactant in fluorous oil/water emulsified systems and in microfluidic circuits. This journal is © The Royal Society of Chemistry 2013

A systematic map of studies testing the relationship between temperature and animal reproduction

1. Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large-scale summaries of the evidence for effect of temperature on reproduction. 2. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). 3. Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. 4. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non-arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short-term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid-latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. 5. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta-analyses, and direct future studies aiming to fill identified gaps

Genetic correlations between temperature-induced plasticity of life-history traits in a soil arthropod.

Temperature is considered one of the most important mediators of phenotypic plasticity in ectotherms. However, the costs and benefits shaping the evolution of different thermal responses are poorly elucidated. One of the possible constraints to phenotypic plasticity is its intrinsic genetic cost, such as genetic linkage or pleiotropy. Genetic coupling of the thermal response curves for different life history traits may significantly affect the evolution of thermal sensitivity in thermally fluctuating environments. We used the collembolan Orchesella cincta to study if there is genetic variation in temperature-induced phenotypic plasticity in life history traits, and if the degree of temperature-induced plasticity is correlated across traits. Egg development rate, juvenile growth rate and egg size of 19 inbred isofemale lines were measured at two temperatures. Our results show that temperature was a highly significant factor for all three traits. Egg development rate and juvenile growth rate increased with increasing temperature, while egg size decreased. Line by temperature interaction was significant for all traits tested; indicating that genetic variation for temperature-induced plasticity existed. The degree of plasticity was significantly positively correlated between egg development rate and growth rate, but plasticity in egg size was not correlated to the other two plasticity traits. The findings suggest that the thermal plasticities of egg development rate and growth rate are partly under the control of the same genes or genetic regions. Hence, evolution of the thermal plasticity of traits cannot be understood in isolation of the response of other traits. If traits have similar and additive effects on fitness, genetic coupling between these traits may well facilitate the evolution of optimal phenotypes. However, for this we need to know the selective forces under field conditions. © 2010 Springer Science+Business Media B.V

A Path Following Controller for the Dynamic Model of a Marine Surface Vessel

A path following controller for the dynamic model of an underactuated marine vessel is presented. The solution extends previous results relative to the purely kinematics case and is able to cope with constant and known ocean currents. Based on kinematics, a reference linear and angular velocity is computed such that if the vehicle had such velocities the path following problem would be asymptotically solved. Then, applying feedback linearization to the dynamic model of the surface vessel, yaw torque and surge force commands are computed in order to drive the vessels total velocity on the desired reference values. The resulting control laws for the yaw and surge degrees of freedom result in nonlinear terms (from feedback linearization) and PI terms. Numerical simulations are provided to validate the proposed approach