Bolus administration of obestatin does not change glucose and insulin levels neither in the systemic nor in the portal circulation of the rat

Obestatin is a second peptide derived from the preproghrelin polypeptide. It was originally thought to have anorexigenic effects, thereby functioning as an antagonist of ghrelin. However, this has been a subject of debate ever since. Since acylated ghrelin strongly induces insulin resistance, it could be hypothesized that obestatin plays a role in glucose homeostasis as well. In the present study we evaluated the effect of obestatin on glucose and insulin metabolism in the systemic and portal circulation. Obestatin 200 nmol/kg was administered systemically as a single intravenous bolus injection to fasted pentobarbital anesthetized adult male Wistar rats. Up to 50 min after administration, blood samples were taken to measure glucose and insulin concentrations, both in the portal and in the systemic circulation. The effect of obestatin was evaluated in fasted and in glucose-stimulated conditions (IVGTT) and compared to control groups treated with saline or IVGTT, respectively. Intravenous administration of obestatin did not have any effect on glucose and insulin concentrations, neither systemic nor portal, when compared to the control groups. Only the glucose peak 1 min after administration of IVGTT was slightly higher in the obestatin treated rats: 605.8 ± 106.3% vs. 522.2 ± 47.1% in the portal circulation, respectively (NS), and 800.7 ± 78.7% vs. 549.6 ± 37.0% in the systemic circulation, respectively (P < 0.02), but it can be debated whether this has any clinical relevance. In the present study, we demonstrated that intravenously administered obestatin does not influence glucose and insulin concentrations, neither in the portal nor in the systemic circulation.     

Neural and cardiovascular responses to emotional stress in humans

Sympathetic neural responses to mental stress are well documented but controversial, whereas sympathetic neural responses to emotional stress are unknown. The purpose of this study was to investigate neural and cardiovascular responses to emotional stress evoked by negative pictures and reexamine the relationship between muscle sympathetic nerve activity (MSNA) and perceived stress. Mean arterial pressure (MAP), heart rate (HR), MSNA, and perceived stress levels were recorded in 18 men during three randomized trials: 1) neutral pictures, 2) negative pictures, and 3) mental stress. MAP and HR increased during mental stress (Delta14 +/- 2 mmHg and Delta15 +/- 2 beats/min, P < 0.001) but did not change during viewing of negative or neutral pictures. MSNA did not change during viewing of neutral (Delta1 +/- 1 burst/min, n = 16) or negative (Delta0 +/- 1 burst/min, n = 16) pictures or during mental stress (Delta1 +/- 2 burst/min, n = 13). Perceived stress levels were higher during mental stress (3 +/- 0 arbitrary units) than during viewing negative pictures (2 +/- 0 arbitrary units, P < 0.001). Perceived stress levels were not correlated to changes in MSNA during negative pictures (r = 0.10, P = 0.84) or mental stress (r = 0.36, P = 0.23). In conclusion, our results demonstrate robust increases in MAP and HR during mental stress, but not during emotional stress evoked by negative pictures. Although the influence of mental stress on MSNA remains unresolved, our findings challenge the concept that perceived stress levels modulate MSNA during mental stress.     

Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells

Abstract Monoamine oxidase A (MAO-A) expression is associated with high-grade prostate cancer. Immunohistochemistry showed that MAO-A is also expressed in the basal epithelial cells of normal prostate glands. Using cultured primary prostatic epithelial cells as a model, we showed that MAO-A prevents basal epithelial cells from differentiating into secretory cells. Under differentiation-promoting conditions, clorgyline, an irreversible MAO-A inhibitor, induced secretory cell-like morphology and repressed expression of cytokeratin 14, a basal cell marker. More importantly, clorgyline induced mRNA and protein expression of androgen receptor (AR), a hallmark of secretory epithelial cells. In clorgyline-treated cells, androgen induced luciferase activity controlled by the promoter of prostate-specific antigen, an AR target gene, in a dose-dependent manner. This activity was blocked by the AR antagonist Casodex, showing that AR is functional. In turn, androgen decreased MAO-A expression in clorgyline-treated, secretory-like cells. Our results demonstrated that cultured basal epithelial cells have the potential to differentiate into secretory cells, and that inhibition of MAO-A is a key factor in promoting this process. Increased expression of MAO-A in high-grade prostate cancer may be an important contributor to its de-differentiated phenotype, raising the possibility that MAO-A inhibition may restore differentiation and reverse the aggressive behavior of high-grade cancer.     

A novel method for estimating the strength of positive mating preference by similarity in the wild

Mating preference can be a driver of sexual selection and assortative mating and is, therefore, a key element in evolutionary dynamics. Positive mating preference by similarity is the tendency for the choosy individual to select a mate which possesses a similar variant of a trait. Such preference can be modelled using Gaussian‐like mathematical functions that describe the strength of preference, but such functions cannot be applied to empirical data collected from the field. As a result, traditionally, mating preference is indirectly estimated by the degree of assortative mating (using Pearson's correlation coefficient, r) in wild captured mating pairs. Unfortunately, r and similar coefficients are often biased due to the fact that different variants of a given trait are nonrandomly distributed in the wild, and pooling of mating pairs from such heterogeneous samples may lead to “false–positive” results, termed “the scale‐of‐choice effect” (SCE). Here we provide two new estimators of mating preference (C_rough and C_scaled) derived from Gaussian‐like functions which can be applied to empirical data. Computer simulations demonstrated that r coefficient showed robust estimations properties of mating preference but it was severely affected by SCE, C_rough showed reasonable estimation properties and it was little affected by SCE, while C_scaled showed the best properties at infinite sample sizes and it was not affected by SCE but failed at biological sample sizes. We recommend using C_rough combined with the r coefficient to infer mating preference in future empirical studies.     

A biophysical model for plant cell plate maturation based on the contribution of a spreading force

Plant cytokinesis, a fundamental process of plant life, involves de novo formation of a “cell plate” partitioning the cytoplasm of dividing cells. Cell plate formation is directed by orchestrated delivery, fusion of cytokinetic vesicles, and membrane maturation to form a nascent cell wall by timely deposition of polysaccharides. During cell plate maturation, the fragile membrane network transitions to a fenestrated sheet and finally a young cell wall. Here, we approximated cell plate sub-structures with testable shapes and adopted the Helfrich-free energy model for membranes, including a stabilizing and spreading force, to understand the transition from a vesicular network to a fenestrated sheet and mature cell plate. Regular cell plate development in the model was possible, with suitable bending modulus, for a two-dimensional late stage spreading force of 2–6 pN/nm, an osmotic pressure difference of 2–10 kPa, and spontaneous curvature between 0 and 0.04 nm⁻¹. With these conditions, stable membrane conformation sizes and morphologies emerged in concordance with stages of cell plate development. To reach a mature cell plate, our model required the late-stage onset of a spreading/stabilizing force coupled with a concurrent loss of spontaneous curvature. Absence of a spreading/stabilizing force predicts failure of maturation. The proposed model provides a framework to interrogate different players in late cytokinesis and potentially other membrane networks that undergo such transitions. Callose, is a polysaccharide that accumulates transiently during cell plate maturation. Callose-related observations were consistent with the proposed model’s concept, suggesting that it is one of the factors involved in establishing the spreading force.

The late-stage onset of an “areal” spreading and stabilizing force is essential for regular plant cell plate development and maturation.     

Independence of the Sodium and Potassium Conductance Channels: A Kinetic Argument

Tightly coupled models for the sodium and potassium conductance changes, in which the potassium “on” process is intimately related to the sodium “on” and “off” processes, are studied. It is shown that such coupled models are incapable of simultaneously showing the observed effects of conditioning potentials on sodium inactivation and on the translation of the potassium conductance in time. It is concluded that the primary mechanisms for the sodium and potassium channels are probably independent.     

Amino acid distribution in some fungal melanins and of soil humic acids from Brazil

Summary Humic acids from four Brazilian topsoils of different origins and four soil fungal melanins, synthesized under two cultural conditions, were subjected to 6N HCl hydrolysis and their amino acid distribution patterns qualitatively and quantitatively determined. Both soil and fungal polymers showed similar patterns with aspartic acid, glutamic acid, glycine and alanine as the dominant amino acids. Some variations noted were more quantitative than qualitative, the similarities were more pronounced than differences, indicating that the fungal melanins may play a significant role in the formation of soil humic acid polymers. The humic acids of Brazilian soils had amino acid distribution patterns similar to those reported for humic acids of other tropical and temperate soils.     

The evolutionary forces maintaining a wild polymorphism of Littorina saxatilis: model selection by computer simulations

Two rocky shore ecotypes of Littorina saxatilis from north-west Spain live at different shore levels and habitats and have developed an incomplete reproductive isolation through size assortative mating. The system is regarded as an example of sympatric ecological speciation. Several experiments have indicated that different evolutionary forces (migration, assortative mating and habitat-dependent selection) play a role in maintaining the polymorphism. However, an assessment of the combined contributions of these forces supporting the observed pattern in the wild is absent. A model selection procedure using computer simulations was used to investigate the contribution of the different evolutionary forces towards the maintenance of the polymorphism. The agreement between alternative models and experimental estimates for a number of parameters was quantified by a least square method. The results of the analysis show that the fittest evolutionary model for the observed polymorphism is characterized by a high gene flow, intermediate-high reproductive isolation between ecotypes, and a moderate to strong selection against the nonresident ecotypes on each shore level. In addition, a substantial number of additive loci contributing to the selected trait and a narrow hybrid definition with respect to the phenotype are scenarios that better explain the polymorphism, whereas the ecotype fitnesses at the mid-shore, the level of phenotypic plasticity, and environmental effects are not key parameters.     

Equine infection with Leishmania in Portugal

The present report describes the first case of equine leishmaniasis in Portugal. Leishmania infection was detected in one animal, which presented an ulcerated skin lesion. Diagnosis was based on serology by CIE, and parasite DNA detection by real-time PCR using a probe specific for L. infantum. This finding requests further leishmaniasis equine surveys in order to clarify the role of the horse as reservoir host in european endemic areas.