1-Aminocyclopentane-1,2,4-tricarboxylic acids screening on glutamatergic and serotonergic systems

Enantiopure constrained 1-aminocyclopentane-1,2,4-tricarboxylic acids containing the glutamic acid skeleton were prepared as two diastereomers characterized by having the carboxylic groups in position two and four cis-oriented to each other and trans with respect to 1-carboxylic group and all cis-oriented carboxylic groups, respectively. A biochemical screening of activity of the above amino acids was investigated on glutamate and 5-HT receptors to find a possible metabotropic agonist, acting on the serotoninergic system.     

Integration of life cycle assessment into a decision support system for selecting sustainable road asphalt pavement mixtures prepared with waste

The International Journal of Life Cycle Assessment - A challenge that the road paving sector is facing concerns the achievement of highly performing bituminous asphalt mixture solutions that do not...     

Antiviral activity of seed extract from Citrus bergamia towards human retroviruses

The effects of an extract from Citrus bergamia (BSext) and those of two products purified from the same extract, that is, nomilin and limonin, and reference compounds, towards HTLV-1 have been reported. Moreover, they were also compared with those obtained towards HIV-1. Results showed that the efficacy of both BSext and limonin in inhibiting HTLV-1 as well as HIV-1 expression in infected cells, as evaluated by comparable quantitative assays, was close to that of the effective, reference compounds, respectively. The protective effect of BSext and of the purified products was associated with the inhibition of both HTLV-1 and HIV-1 RT activities in conceptually similar, cell-free assays. The cytotoxicity of the assayed compounds of natural origin was substantially less pronounced than that of the reference compounds, thus showing a favourable selectivity index for the novel BSext product.     

Measuring the size of biological nanostructures with spatially modulated illumination microscopy

Spatially modulated illumination fluorescence microscopy can in theory measure the sizes of objects with a diameter ranging between 10 and 200 nm and has allowed accurate size measurement of subresolution fluorescent beads ( approximately 40-100 nm). Biological structures in this size range have so far been measured by electron microscopy. Here, we have labeled sites containing the active, hyperphosphorylated form of RNA polymerase II in the nucleus of HeLa cells by using the antibody H5. The spatially modulated illumination-microscope was compared with confocal laser scanning and electron microscopes and found to be suitable for measuring the size of cellular nanostructures in a biological setting. The hyperphosphorylated form of polymerase II was found in structures with a diameter of approximately 70 nm, well below the 200-nm resolution limit of standard fluorescence microscopes.     

Optimization of α-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site

We have optimized a novel series of potent p38 MAP kinase inhibitors based on an α-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions.     

Foraging behaviour and diet of the Alpine ChoughPyrrhocorax graculus in the Italian Alps in summer

Summary The foraging behaviour of the Alpine Chough was studied around Cervinia (Aosta, Italy) in June and July 1989 and 1990. The birds foraging in loose flocks (of mean size 32.4) which flew to new foraging patches at very frequent intervals (median stay time 74.5 s in 1989 and 75.0 s in 1990). The Choughs' peck rates declined significantly through the summer, from around 17 items per min in mid-June to around 9 per min in late July. Examination of faeces and regurgitated pellets showed that the most common food items were Orthoptera (grasshoppers) which occurred in 83 % of samples, Coleoptera Curculionidae (55 %) and Elateridae (27 %), invertebrate eggs (26 %), Lepidopteran larvae (24 %), Hymenoptera Formicidae (18 %) and vegetable matter (18 %). Grasshoppers remained very small until mid-July and varied greatly in size and density between different parts of the study area. The Choughs' very short stay time in any one patch of meadow is consistent with their high intake rates and apparently low costs of movement between feeding sites, but they may also be sampling in a highly variable environment.

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Zusammenfassung Die Nahrungssuche von AlpendohlenPyrrhocorax graculus wurde im Juni und Juli 1989 und 1990 in der Umgebung von Cervinia (Aosta, Italien) untersucht. Die Vögel bewegten sich in losen Gruppen (mittlere Gruppengröße 32,3) und wechselten in regelmäßigen Intervallen zu neuen Futterplätzen (Median der Aufenthaltsdauer 74,5 s 1989 und 75,0 s 1990). Die Pickraten der Alpendohlen nahmen im Lauf des Sommers signifikant von ca. 17 Objekten (Mitte Juni) auf 9 pro min (Ende Juli) ab. Untersuchungen von Kot, Gewöllen und einem Magen erbrachten als häufigste Nahrungsbestandteile Geradflügler (wahrscheinlich Heuschrecken) in 83 % der Proben, Käfer Curculionidae (55 %) und Elateridae (27 %), Eier von Wirbellosen (26 %), Schmetterlingslarven (24 %), Ameisen (18 %) und pflanzliches Material (18 %). Heuschrecken blieben bis Mitte Juli sehr klein und unterschieden sich in verschiedenen Teilen des Untersuchungsgebietes beträchtlich in Größe und Dichte. Die sehr kurze Aufenthaltsdauer der Alpendohlen an allen Futterplätzen stimmt mit ihren hohen Nahrungsaufnahmeraten und den offensichtlich niedrigen Kosten für Ortsveränderungen zwischen den Plätzen überein; es ist aber ebensogut möglich, daß die Beutedichte in den genutzten Gebieten sehr variabel ist.

     

Experimental chronic low‐frequency resistance training produces skeletal muscle hypertrophy in the absence of muscle damage and metabolic stress markers

Volitional animal resistance training constitutes an important approach to modeling human resistance training. However, the lack of standardization protocol poses a frequent impediment to the production of skeletal muscle hypertrophy and the study of related physiological variables (i.e., cellular damage/inflammation or metabolic stress). Therefore, the purposes of the present study were: (1) to test whether a long‐term and low frequency experimental resistance training program is capable of producing absolute increases in muscle mass; (2) to examine whether cellular damage/inflammation or metabolic stress is involved in the process of hypertrophy. In order to test this hypothesis, animals were assigned to a sedentary control (C, n = 8) or a resistance trained group (RT, n = 7). Trained rats performed 2 exercise sessions per week (16 repetitions per day) during 12 weeks. Our results demonstrated that the resistance training strategy employed was capable of producing absolute mass gain in both soleus and plantaris muscles (12%, p < 0.05). Furthermore, muscle tumor necrosis factor (TNF‐α) protein expression (soleus muscle) was reduced by 24% (p < 0.01) in trained group when compared to sedentary one. Finally, serum creatine kinase (CK) activity and serum lactate concentrations were not affected in either group. Such information may have practical applications if reproduced in situations where skeletal muscle hypertrophy is desired but high mechanical stimuli of skeletal muscle and inflammation are not. Copyright © 2010 John Wiley & Sons, Ltd.     

The NAD(P)H:Quinone Oxidoreductase 1 induces cell cycle progression and proliferation of melanoma cells

The oxidoreductase NQO1 plays a prominent role in maintaining the cellular homeostasis. NQO1 is mainly a cytosolic enzyme which catalyzes the metabolism of quinones and is present in almost all tissue types providing protection against different stresses including xenobiotics, oxidants, UV light, and ionizing radiation. This enzyme is overexpressed in many cancerous tissues and its function in carcinogenesis remains unclear. Due to the relative lack of information on the role of NQO1 in melanoma pathogenesis, we attempted to determine the expression and basic function of NQO1 in melanoma cell proliferation. We found that NQO1 is overexpressed in most melanoma cell lines with respect to melanocytes. Furthermore, the expression of this oxidoreductase significantly induces cell cycle progression by upregulating the expression of cyclins A2, B1 and D1, leading to the proliferation of melanoma cells. Our results also indicate that NQO1 is an upstream regulator of NF-κB p50, a factor linked to melanoma progression and poor patient prognosis. Interestingly, we found that NQO1 stabilizes the transactivator BCL3, which in turn upregulates NF-κB p50. More importantly, our results also indicate that NF-κB p50 correlates with the expression of NQO1 and mediates its role in the proliferation of melanoma cells.     

Occurrence of two architectural types of hexagonal bilayer hemoglobin in annelids: comparison of 3D reconstruction volumes of Arenicola marina and Lumbricus terrestris hemoglobins

A 3D reconstruction at 25 A resolution of native hemoglobin of the polychaete worm Arenicola marina was carried out from frozen-hydrated specimens examined in the electron microscope. The reconstruction volume of this large extracellular multimeric respiratory pigment appears as a hexagonal bilayer structure with eclipsed vertices in its upper and lower hexagonal layers. Conversely, in hemoglobins of oligochaetes, achaetes, and vestimentiferans and in chlorocruorins of the Sabellidae (polychaete) family, the vertices of the upper layer are 16 degrees clockwise rotated with respect to those of the lower layer. The fact that two other polychaete hemoglobins (Alvinella pompejana and Tylorrhynchus heterochaetus) have the same architecture as Arenicola led us to define two types of hexagonal bilayer hemoglobins/chlorocruorins: (i) type-I present in oligochaete, achaete, and vestimentiferan hemoglobins and in Sabellidae chlorocruorins; and (ii) type-II present in polychaete hemoglobins. A comparative study of the hemoglobins of Lumbricus terrestris (type-I) and Arenicola marina (type-II) showed that only two small differences located in the c4 and c5 linking units are responsible of the important architectural difference present in oligomers. A likely scheme proposed to explain the phylogenic distribution of the two types suggests that Clitellata, Sabellida (polychaete), and vestimentiferan hemoglobins and chlorocruorins derive from a type-I ancestral molecule, while Terebellida (Alvinella), Phyllodocida (Tylorrhynchus), and Scolecida (Arenicola) and possibly other polychaetes derive from an ancestor molecule with type-II hemoglobin. The architectures of the hollow globular substructures are highly similar in Arenicola and Lumbricus hemoglobins, with 12 globin chains and three linking units (c3a, c3b, and c4). The central piece of Arenicola hemoglobin is an ellipsoid while that of Lumbricus is a toroid. No phylogenic correlation could be found between the structure of the central pieces and the architecture type.