Nuclear diacylglycerol kinases: emerging downstream regulators in cell signaling networks

There exists an active lipid metabolism in the nucleus, which is regulated differentially from the lipid metabolism taking place elsewhere in the cell. Evidence has been accumulated that nuclear lipid metabolism is closely involved in a variety of cell responses, including proliferation, differentiation, and apoptosis. A fundamental lipid second messenger which is generated in the nucleus is diacylglycerol, that is mainly known for its role as an activator of some protein kinase C isoforms. Diacylglycerol kinases attenuate diacylglycerol signaling by converting this lipid to phosphatidic acid, which also has signaling functions. Ten mammalian diacylglycerol kinase isoforms have been cloned so far, and some of them are found also in the nucleus, either as resident proteins or after migration from cytoplasm in response to various agonists. Experiments using cultured cells have demonstrated that nuclear diacylglycerol kinases have prominent roles in cell cycle regulation and differentiation. In this review, the emerging roles played by diacylglycerol kinases in the nucleus, such as the control of G1/S phase transition, are discussed.     

Fine structure of spermatozoa in the gilthead sea bream (Sparus aurata Linnaeus, 1758) (Perciformes, Sparidae)

Scanning and transmission electron microscopy were used to investigate the fine structure of the sperm of the sparid fish Sparus aurata L. The mature spermatozoon of gilthead sea bream belongs, like that of the other sparid fish, to a "type I" as defined by Mattei (1970). It has a spherical head which lacks an acrosome, a short, irregularly-shaped midpiece and a long cylindrical tail. The nucleus reveals a deep invagination (nuclear fossa) in which the centriolar complex is located. The two centrioles are approximately perpendicular to each other and show a conventional "9+0" pattern. The proximal centriole is associated with a cross-striated cylindrical body lying inside a peculiar satellite nuclear notch which appears as a narrow invagination of the nuclear fossa. The distal centriole is attached to the nuclear envelope by means of a lateral plate and radial fibres made of an electron-dense material. The short midpiece houses one mitochondrion. The flagellum is inserted perpendicularly into the base of the nucleus and contains the conventional 9+2 axoneme.     

Glucocorticoid levels in free ranging resident mantled howlers: a study of coping strategies

A growing amount of data shows that a preference for passive-nonaggressive over active-aggressive problem solving is associated with higher levels of glucocorticoids (GC). For mantled howlers, the arrival of an adult male in a new group is a potential source of psychological stress for both resident males and females. Resident mantled howler males take an active stand and aggressively repel the entrance of solitary males, while females take a passive-nonaggressive stand. In order to study whether the relationship between coping strategies and the activation of the hypothalamic-pituitary-adrenal (HPA) axis observed in other species applies to the response of resident mantled howlers to the presence of solitary males, we examine the relationship between different group and subpopulation variables and the GC levels measured in feces collected from 10 groups living in six forest fragments, in Los Tuxtlas, Mexico. The results of our study suggest that the resident mantled howler females' passive response to the presence of solitary males is accompanied by the activation of the HPA axis, whereas resident males' aggressive response is not accompanied by any changes in the HPA axis. In contrast, a previous study suggests that resident male howlers respond by increasing their testosterone levels to the presence of solitary males (Cristobal-Azkarate et al., Hormones and Behavior 2006;49 261-267).These different behavioral and hormonal responses coincide with the active and passive coping styles described for other species. The conditions in which howlers live in our study area may be favoring the interaction between solitary and resident howlers, and inducing chronically high GC levels, which in turn could negatively affect the fitness of these subpopulations.     

Sensitivity of the invasive geophyte Oxalis pes-caprae to nutrient availability and competition

BACKGROUND AND AIMS: Invasion by alien plants may be partially related to disturbance-related increases in nutrient availability and decreases of competition with native species, and to superior competitive ability of the invader. Oxalis pes-caprae is an invasive winter geophyte in the Mediterranean Islands that reproduces vegetatively via bulbs. An investigation was made into the relative responses of O. pes-caprae and the native annual grass Lolium rigidum to nutrient availability and to competition with each other in order to understand patterns of invasion in the field. Because Oxalis accumulates oxalic acid in its leaves, which could ameliorate soil phosphorous availability, field observations were made to determine whether the presence of Oxalis alters soil P availability. METHODS: A full-factorial glasshouse experiment was conducted with nutrient availability (high and low) and competition (Lolium alone, Oxalis alone, and Lolium and Oxalis together). Plant performance was assessed by determining (1) above- and below-ground biomass at the time of Oxalis maximum biomass and (2) reproductive output of Oxalis and Lolium at the end of their respective growth cycles. Measurements were also taken for leaf N and P content. Soil samples were taken in the field from paired Oxalis-invaded and non-invaded plots located in Menorca (Balearic Islands) and available P was determined. KEY RESULTS: High nutrient availability increased Oxalis and Lolium vegetative biomass and reproductive output to a similar degree. Competition with Lolium had a much stronger negative effect on Oxalis bulb production than reduced nutrients. Lolium was a superior competitor than Oxalis; the latter did not affect Lolium maximum biomass and spike production. Significantly greater soil-P availability in Oxalis-invaded field soils relative to paired non-invaded soils suggest that Oxalis influences soil P cycling. CONCLUSIONS: Oxalis is a poor competitor. This is consistent with the preferential distribution of Oxalis in disturbed areas such as ruderal habitats, and might explain its low influence on the cover of native species in invaded sites. The results also suggest that certain disturbances (e.g. autumn ploughing) may greatly enhance Oxalis invasion.     

The role of sex in parasite dynamics: model simulations on transmission of Heligmosomoides polygyrus in populations of yellow-necked mice, Apodemus flavicollis

We investigated possible mechanisms that could cause sex-biased parasite transmission of the helminth Heligmosomoides polygyrus in its rodent host, Apodemus flavicollis, using a modelling approach. Two, not mutually exclusive, hypotheses were examined: that sex-biased parasite transmission is caused by differences in immunity that influence the success of free-living stages and/or is caused by sex differences in host behaviour and the dissemination of infective stages. Model simulations were compared with results from a field manipulation experiment of H. polygyrus in replicated populations of A. flavicollis. Simulations predicted the experimental field results, and both hypotheses explained the pattern observed. Transmission is male-biased if a male immune response increases fertility, hatching or survival of free-living stages. Alternatively, transmission is male-biased if their behavioural characteristics allow them to spread infective larvae in areas more frequently used by females. These results highlight that host sex is not only responsible for differences in parasite susceptibility, but may profoundly influence host-parasite interactions, resulting in a sex bias in parasite transmission.     

Cortical control of grasp in non-human primates

The skilled use of the hand for grasping and manipulation of objects is a fundamental feature of the primate motor system. Grasping movements involve transforming the visual information about an object into a motor command appropriate for the coordinated activation of hand and finger muscles. The cerebral cortex and its descending projections to the spinal cord are known to play a crucial role for the control of grasp. Recent studies in non-human primates have provided some striking new insights into the respective contribution of the parietal and frontal motor cortical areas to the control of grasp. Also, new approaches allowed investigating the coupling of grasp-related activity in different cortical areas for the control of the descending motor command.     

New 1,8-naphthyridine and quinoline derivatives as CB2 selective agonists

A series of new 1,8-naphthyridine and quinoline derivatives were synthesized and evaluated for their cannabinoid receptor affinity. In particular, compounds 2, 5, 11, and 13 showed a high CB(2) affinity and CB(2) versus CB(1) selectivity, in agreement with molecular modeling studies. Furthermore, compound 2 also exhibited in vivo antinociceptive effects.     

Synthesis and biological evaluation of non-peptide alpha(v)beta(3)/alpha(5)beta(1) integrin dual antagonists containing 5,6-dihydropyridin-2-one scaffolds

Small constrained non-peptidic molecules consisting of a polyfunctionalized rigid core, carrying appendages corresponding to arginine and aspartic acid side chains, have been recently reported to be promising for drug development. In this work, the 5,6-dihydropyridin-2-one was envisaged as a scaffold to turn into potential integrin ligands, introducing a carboxylic acid and a basic appendage. The synthesis and the antiadhesion activity of a small library of peptidomimetics capable to recognize alpha(v)beta(3) and alpha(5)beta(1) integrins has been herein reported.     

Utility of large-scale transiently transfected cells for cell-based high-throughput screens to identify transient receptor potential channel A1 (TRPA1) antagonists

Despite increasing use of cell-based assays in high-throughput screening (HTS) and lead optimization, one challenge is the adequate supply of high-quality cells expressing the target of interest. To this end, cell lines stably expressing targets are often established, maintained, and scaled up by cell culture. These steps require large investments of time and resources. Moreover, significant variability invariably occurs in cell yield, viability, expression levels, and target activities. In particular, stable expression of targets such as transient receptor potential A1 (TRPA1) causes toxicity, cell line degeneration, and loss of functional activity. Therefore, in an effort to identify TRPA1 antagonists, the authors used large-scale transiently transfected (LSTT) cells, enabling rapid establishment of assays suitable for HTS. LSTT cells, which could- be stored frozen for a long period of time (e.g., at least 42 weeks), retained TRPA1 protein expression and could be easily revived to produce robust and consistent signals in calcium influx and electrophysiological assays. Using cells from a single transfection, a chemical library of 700,000 compounds was screened, and TRPA1 antagonists were identified. The use of LSTT circumvented issues associated with stable TRPA1 expression, increased flexibility and consistency, and greatly reduced labor and cost. This approach will also be applicable to other pharmaceutical targets.