Design and synthesis of S-(-)-2-[[4-(napht-1-yl)piperazin-1-yl]methyl]-1,4-dioxoperhydropyrrolo[1,2-a]pyrazine (CSP-2503) using computational simulation. A 5-HT1A receptor agonist

Based on a computational model for 5-HT(1A)R-ligand interaction and QSAR studies, we have designed and synthesized a new series of arylpiperazines 2-8 which exhibit high 5-HT(1A)R affinity and selectivity over alpha(1)-adrenergic receptors. Among them, compound CSP-2503 (4) has been pharmacologically characterized as a 5-HT(1A)R agonist at somatodendritic and postsynaptic sites, endowed with anxiolytic properties.     

Influence of different neural systems on the secretion of sex hormones in potassium deficient mice

The influence of different neural systems that modulate GnRH secretion by hypothalamic neurons was investigated in mice exposed to hypokalemic conditions, in which the pulsatile release of GnRH has been shown to be altered and associated with a significant decrease of plasma sex steroids. Our results demonstrate that the potentiation of the inhibitory pathways mediated by opiates and GABA may be implicated in the decrease of sex hormones secretion produced by hypokalemia since treatment with higher doses of naloxone or flumazenil are required to restore progesterone or testosterone levels in potassium deficient mice. The combination treatment of prazoxin and naloxone suggests that the inhibitory action of opiates take place through its action on noradrenergic neurons. It is also possible that the inhibition of GnRH release could be due to a decrease in the tonic stimulatory action of noradrenergic pathway implicated in the control of GnRH release. Our results also reveal that it is unlikely that the glutamatergic system may play any relevant direct role in the decrease of sex steroid secretion observed in potassium deficient mice. Finally, these results together with the normal pattern of estradiol levels found along the estrus cycle in potassium deficient mice indicate that factors different from estradiol and acting on neural systems implicated in the regulation of GnRH-secreting neurons participate in the generation of the preovulatory surge of GnRH.     

Life in proto‐Amazonia: Middle Miocene mammals from the Fitzcarrald Arch (Peruvian Amazonia)

The Middle Miocene has been identified as a time of great diversification in modern lineages now distributed in tropical South America, and when basic archetypal traits defining Amazonia appear, including climatic humid conditions, basic floral physiognomy and phylogenetic composition of modern rainforests. Nonetheless, Middle Miocene localities in South America are poorly known, especially at low latitudes where only one species‐rich locality, La Venta in Colombia, has been extensively studied. The present contribution describes the mammal fauna of Fitzcarrald, a new Middle Miocene local fauna from western Amazonia in Peru. Fitzcarrald is correlated with the Laventan South American Land Mammal Age based on the presence of taxa defining the ‘Miocochilius assemblage zone’ in La Venta. The mammalian fauna of Fitzcarrald comprises 24 taxa among cingulates, folivores, astrapotheres, notoungulates, litopterns, rodents, odontocetes and a possible marsupial. At this time, tropical South America was characterized by the presence of the Pebas megawetland, a huge lacustrine complex that provided unique ecological and environmental conditions most likely isolating northern South America from southern South America. These isolating conditions might have come to an end with its disappearance in the Late Miocene and the establishment of the subsequent Acre system, the predecessor fluvial system of modern Amazonia. Results of faunistic similarity between Fitzcarrald and other Miocene faunas throughout South America support these scenarios. The Fitzcarrald mammal fauna exhibits first appearance datums and last appearance datums of various taxa, showing that tropical South America has played a crucial role in the evolutionary history and biogeography of major clades, and revealing a more complex biological history than previously proposed, based on the record from the southern cone of the continent.     

GUVs Melt Like LUVs: The Large Heat Capacity of MLVs Is Not Due to Large Size or Small Curvature

The excess heat capacity functions (ΔC_p) associated with the main phase transition of large unilamellar vesicles (LUVs) and multilamellar vesicles (MLVs) are very different. Two explanations are possible. First, the difference in vesicle size (curvature) results in different gel-fluid interactions in the membrane; those interactions have a large effect on the cooperativity of the phase transition. Second, there is communication between the bilayers in an MLV when they undergo the gel-fluid transition; this communication results in thermodynamic coupling of the phase transitions of the bilayers in the MLV and, consequently, in an apparent increase in the cooperativity of the transition. To test these hypotheses, differential scanning calorimetry was performed on giant unilamellar vesicles (GUVs) of pure dipalmitoylphosphatidylcholine. The ΔC_p curve of GUVs was found to resemble that of the much smaller LUVs. The transition in GUVs and LUVs is much broader (half-width ∼1.5°C) than in MLVs (∼0.1°C). This similarity in GUVs and LUVs indicates that their size has little effect on gel-fluid interactions in the phase transition. The result suggests that coupling between the transitions in the bilayers of an MLV is responsible for their apparent higher cooperativity in melting.     

Rationale for the design of shortened derivatives of the NK-lysin-derived antimicrobial peptide NK-2 with improved activity against Gram-negative pathogens

The peptide NK-2 is an effective antimicrobial agent with low hemolytic and cytotoxic activities and is thus a promising candidate for clinical applications. It comprises the alpha-helical, cationic core region of porcine NK-lysin a homolog of human granulysin and of amoebapores of pathogenic amoeba. Here we visualized the impact of NK-2 on Escherichia coli by electron microscopy and used NK-2 as a template for sequence variations to improve the peptide stability and activity and to gain insight into the structure/function relationships. We synthesized 18 new peptides and tested their activities on seven Gram-negative and one Gram-positive bacterial strains, human erythrocytes, and HeLa cells. Although all peptides appeared unordered in buffer, those active against bacteria adopted an alpha-helical conformation in membrane-mimetic environments like trifluoroethanol and negatively charged phosphatidylglycerol (PG) liposomes that mimick the cytoplasmic membrane of bacteria. This conformation was not observed in the presence of liposomes consisting of zwitterionic phosphatidylcholine (PC) typical for the human cell plasma membrane. The interaction was paralleled by intercalation of these peptides into PG liposomes as determined by FRET spectroscopy. A comparative analysis between biological activity and the calculated peptide parameters revealed that the decisive factor for a broad spectrum activity is not the peptide overall hydrophobicity or amphipathicity, but the possession of a minimal positive net charge plus a highly amphipathic anchor point of only seven amino acid residues (two helical turns).     

How the emotional content of discourse affects language comprehension

Emotion effects on cognition have often been reported. However, only few studies investigated emotional effects on subsequent language processing, and in most cases these effects were induced by non-linguistic stimuli such as films, faces, or pictures. Here, we investigated how a paragraph of positive, negative, or neutral emotional valence affects the processing of a subsequent emotionally neutral sentence, which contained either semantic, syntactic, or no violation, respectively, by means of event-related brain potentials (ERPs). Behavioral data revealed strong effects of emotion; error rates and reaction times increased significantly in sentences preceded by a positive paragraph relative to negative and neutral ones. In ERPs, the N400 to semantic violations was not affected by emotion. In the syntactic experiment, however, clear emotion effects were observed on ERPs. The left anterior negativity (LAN) to syntactic violations, which was not visible in the neutral condition, was present in the negative and positive conditions. This is interpreted as reflecting modulatory effects of prior emotions on syntactic processing, which is discussed in the light of three alternative or complementary explanations based on emotion-induced cognitive styles, working memory, and arousal models. The present effects of emotion on the LAN are especially remarkable considering that syntactic processing has often been regarded as encapsulated and autonomous.     

Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein

Findings on the association of alcohol consumption and oxidation of low-density lipoprotein (LDL), which is thought to play a crucial role in the generation of atherosclerotic lesion, are inconsistent. The aim of the present study was to investigate the association of total alcohol consumption and type of alcoholic beverage with circulating plasma LDL oxidation. This cross-sectional study included data of circulating oxidized LDL (ox-LDL) from a subpopulation of 587 men and women enrolled in a population-based survey conducted in 2000 in Girona (Spain). Multivariate analysis was performed to describe the independent association of alcohol consumption and ox-LDL. Increasing alcohol consumption was associated with high in vivo ox-LDL levels in the present population. The consumption of 10 g of alcohol was associated with an increase of 2.40 U/L of ox-LDL (p = 0.002). Adjustment for dietary variables, leisure-time physical activity, educational level, smoking, LDL-cholesterol, high-density lipoprotein-cholesterol, glycemia, triglycerides, diabetes, body mass index, waist circumference, and systolic and diastolic blood pressures only slightly modified this association (p = 0.003). In this full adjusted model the consumption of 10 g of alcohol per day was associated with an increase of 2.11 U/L of ox-LDL. Consumption of wine (ml/day) was associated with increasing ox-LDL levels (p = 0.029), however, attenuated after controlling for alcohol. No significant relationship of ox-LDL with alcohol-independent consumption of wine, beer, and spirits was observed. Alcohol consumption was independently and directly associated with circulating ox-LDL in the present population.     

Tropical wetlands for climate change research, water quality management and conservation education on a university campus in Costa Rica

EARTH University is a small agronomic university with a theme of sustainability in eastern Costa Rica. Several natural and constructed wetlands on its campus are used for research, water quality improvement, and higher education. It has become an important location for research and teaching on humid tropical wetland ecology and management. A 112-ha flow-through Raphia taedigera (Arecaceae) forested wetland is being used for climate change research, focusing on carbon sequestration and methane generation. Methane emissions are measured seasonally and are comparable to rates in tropical wetlands published elsewhere. Carbon sequestration by the wetland appears to be substantially higher than similar flow-through temperate zone wetlands. Treatment wetlands are used on campus to improve water quality of effluents from an animal farm, a dairy plant, a landfill, and a banana paper plant. Water quality was substantially improved in all of these wetlands except the landfill leachate wetland. All of these campus wetlands have been integrated into the four-year education program of EARTH University and 22 undergraduate projects have been completed on wetlands over the past 14 years.     

Application of different organic amendments in a gasoline contaminated soil: effect on soil microbial properties

The effects of four organic wastes, including cotton gin crushed compost (CC), poultry manure (PM), sewage sludge (SS) and organic municipal solid waste (MSW) on some biological properties of a Xerollic Calciorthid soil polluted with gasoline at two loading rates (5% and 10%) were studied in an incubation experiment. Three hundred grams of sieved soil (<2mm) were polluted with gasoline and mixed with PM at a rate of 10%, CC at a rate of 17.2%, SS at a rate of 23.1%, or MSW at a rate of 13.1%, applying to the soil the same amount of organic matter with each organic amendment. An unamended soil, non polluted (C) and polluted with gasoline at 5% (G1) and 10% (G2) rate were used as reference. Soil samples were collected after 1, 30, 60, 90, 120, 180 and 270 d of incubation and analyzed for microbial biomass carbon, respiration and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities. At the end of the incubation period, soil biological properties were higher in organic amended soils than in C, G1 and G2 treatments. In particular, soil microbial biomass carbon and dehydrogenase, urease, beta-glucosidase, phosphatase and arylsulfatase activities increased 87.1%, 92.9%, 88.7%, 93.2%, 78.2% and 85.3%, respectively for CC-amended soils respect to G2, 85.7%, 82.3%, 87.3%, 92.2%, 76.7% and 83.6%, respectively for PM-amended soils; 82%, 90%, 84.8%, 89.9%, 74.1% and 80%, respectively for SS-amended soils; and 71.3%, 78.3% 26.2%, 38.2%, 79.7% and 88.6%, respectively for MSW-amended soils. Since the adsorption capacity of gasoline was higher in CC than the PM, SS and MSW-amended soils, it can be concluded that the addition of organic wastes with higher humic acid concentration is more beneficial for remediation of soils polluted with gasoline.