κ-Opioid Signaling in the Lateral Hypothalamic Area Modulates Nicotine-Induced Negative Energy Balance

Several studies have reported that nicotine, the main bioactive component of tobacco, exerts a marked negative energy balance. Apart from its anorectic action, nicotine also modulates energy expenditure, by regulating brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. These effects are mainly controlled at the central level by modulation of hypothalamic neuropeptide systems and energy sensors, such as AMP-activated protein kinase (AMPK). In this study, we aimed to investigate the kappa opioid receptor (κOR)/dynorphin signaling in the modulation of nicotine’s effects on energy balance. We found that body weight loss after nicotine treatment is associated with a down-regulation of the κOR endogenous ligand dynorphin precursor and with a marked reduction in κOR signaling and the p70 S6 kinase/ribosomal protein S6 (S6K/rpS6) pathway in the lateral hypothalamic area (LHA). The inhibition of these pathways by nicotine was completely blunted in κOR deficient mice, after central pharmacological blockade of κOR, and in rodents where κOR was genetically knocked down specifically in the LHA. Moreover, κOR-mediated nicotine effects on body weight do not depend on orexin. These data unravel a new central regulatory pathway modulating nicotine’s effects on energy balance.     

Description of the thermodynamic properties and fluid-phase behavior of aqueous solutions of linear,branched, and cyclic amines

The SAFT-γ Mie group-contribution equation of state is used to represent the fluid-phase behavior of aqueous solutions of a variety of linear, branched, and cyclic amines. New group interactions are developed in order to model the mixtures of interest, including the like and unlike interactions between alkyl primary, secondary, and tertiary amine groups (NH₂, NH, N), cyclic secondary and tertiary amine groups (cNH, cN), and cyclic methine-amine groups (cCHNH, cCHN) with water (H₂O). The group-interaction parameters are estimated from appropriate experimental thermodynamic data for pure amines and selected mixtures. By taking advantage of the group-contribution nature of the method, one can describe the fluid-phase behavior of mixtures of molecules comprising those groups over broad ranges of temperature, pressure, and composition. A number of aqueous solutions of amines are studied including linear, branched aliphatic, and cyclic amines. Liquid–liquid equilibria (LLE) bounded by lower critical solution temperatures (LCSTs) have been reported experimentally and are reproduced here with the SAFT-γ Mie approach. The main feature of the approach is the ability not only to represent accurately the experimental data employed in the parameter estimation, but also to predict the vapor–liquid, liquid–liquid, and vapor–liquid–liquid equilibria, and LCSTs with the same set of parameters. Pure compound and binary phase diagrams of diverse types of amines and their aqueous solutions are assessed in order to demonstrate the main features of the thermodynamic and fluid-phase behavior.     

Fibrinogen as a cardiovascular risk factor in Spanish children and adolescents. The Ni?o Jesus Group

Studies done on adults reveal a significant role of fibrinogen (FG) in cardiovascular disease. The main purpose of our study was to determine the level of plasma FG in children, its distribution according to age and sex, and its relationship to other cardiovascular risk factors such as cigarette smoking, plasma lipid disturbances, and a positive family history for other cardiovascular risk factors. We studied a population of 2224 children, aged 2 to 18 years, from five different schools located in Madrid. We found a significantly higher level of FG in the groups of females aged 6 to 8 and 16 to 18 years than in males of the same ages (p < 0.001). The study population was distributed into two groups according to the plasma fibrinogen level: > 394 mg/dl and < 394 mg/dl. In both groups we determined plasma levels of total cholesterol, triglycerides, and very low-density lipoprotein (VLDL) cholesterol and found these parameters significantly higher in the group with an FG level > 394 mg/dl (p < 0.05).     

A relation between interfacial and bulk properties along the saturation curve

A liquid-vapor interface in thermal equilibrium was considered, where the pressure tensor depends upon the density (z) and the position z. The surface tension coefficient results are parametrized with the bulk compressibility, liquid-vapor density difference, and interfacial width along the saturation curve. Previous results at the triple and critical points reported by other investigators are verified. Also included is a plot of the computed results using the parametric equation and experimental data for different substances.     

Contrasting Rootstock-Mediated Growth and Yield Responses in Salinized Pepper Plants (Capsicum annuum L.) Are Associated with Changes in the Hormonal Balance

Salinity provokes an imbalance of vegetative to generative growth, thus impairing crop productivity. Unlike breeding strategies, grafting is a direct and quick alternative to improve salinity tolerance in horticultural crops, through rebalancing plant development. Providing that hormones play a key role in plant growth and development and stress responses, we hypothesized that rootstock-mediated reallocation of vegetative growth and yield under salinity was associated with changes in the hormonal balance. To test this hypothesis, the hybrid pepper variety (Capsicum annuum L. “Gacela F1”) was either non-grafted or grafted onto three commercial rootstocks (Creonte, Atlante, and Terrano) and plants were grown in a greenhouse under control (0 mM NaCl) and moderate salinity (35 mM NaCl) conditions. Differential vegetative growth versus fruit yield responses were induced by rootstock and salinity. Atlante strongly increased shoot and root fresh weight with respect to the non-grafted Gacela plants associated with improved photosynthetic rate and K⁺ homeostasis under salinity. The invigorating effect of Atlante can be explained by an efficient balance between cytokinins (CKs) and abscisic acid (ABA). Creonte improved fruit yield and maintained the reproductive to vegetative ratio under salinity as a consequence of its capacity to induce biomass reallocation and to avoid Na⁺ accumulation in the shoot. The physiological responses associated with yield stability in Creonte were mediated by the inverse regulation of CKs and the ethylene precursor 1-aminocyclopropane-1-carboxylic acid. Finally, Terrano limited the accumulation of gibberellins in the shoot thus reducing plant height. Despite scion compactness induced by Terrano, both vegetative and reproductive biomass were maintained under salinity through ABA-mediated control of water relations and K⁺ homeostasis. Our data demonstrate that the contrasting developmental and physiological responses induced by the rootstock genotype in salinized pepper plants were critically mediated by hormones. This will be particularly important for rootstock breeding programs to improve salinity tolerance by focusing on hormonal traits.     

CYP154C5 Regioselectivity in Steroid Hydroxylation Explored by Substrate Modifications and Protein Engineering**

CYP154C5 from Nocardia farcinica is a P450 monooxygenase able to hydroxylate a range of steroids with high regio- and stereoselectivity at the 16α-position. Using protein engineering and substrate modifications based on the crystal structure of CYP154C5, an altered regioselectivity of the enzyme in steroid hydroxylation had been achieved. Thus, conversion of progesterone by mutant CYP154C5 F92A resulted in formation of the corresponding 21-hydroxylated product 11-deoxycorticosterone in addition to 16α-hydroxylation. Using MD simulation, this altered regioselectivity appeared to result from an alternative binding mode of the steroid in the active site of mutant F92A. MD simulation further suggested that the entrance of water to the active site caused higher uncoupling in this mutant. Moreover, exclusive 15α-hydroxylation was observed for wild-type CYP154C5 in the conversion of 5α-androstan-3-one, lacking an oxy-functional group at C17. Overall, our data give valuable insight into the structure–function relationship of this cytochrome P450 monooxygenase for steroid hydroxylation.     

gHRV: Heart rate variability analysis made easy

In this paper, the gHRV software tool is presented. It is a simple, free and portable tool developed in python for analysing heart rate variability. It includes a graphical user interface and it can import files in multiple formats, analyse time intervals in the signal, test statistical significance and export the results.     

Titans’ revenge: Detecting Zeus via its own flaws

Malware is one of the main threats to the Internet security in general, and to commercial transactions in particular. However, given the high level of sophistication reached by malware (e.g. usage of encrypted payload and obfuscation techniques), malware detection tools and techniques still call for effective and efficient solutions. In this paper, we address a specific, dreadful, and widely diffused financial malware: Zeus.The contributions of this paper are manifold: first, we propose a technique to break the encrypted malware communications, extracting the keystream used to encrypt such communications; second, we provide a generalization of the proposed keystream extraction technique. Further, we propose Cronus, an IDS that specifically targets Zeus malware. The implementation of Cronus has been experimentally tested on a production network, and its high quality performance and effectiveness are discussed. Finally, we highlight some principles underlying malware—and Zeus in particular—that could pave the way for further investigation in this field.