Ovarian-Steroid Modulation of Locus Coeruleus Activity in Female Rats: Involvement in Luteinising Hormone Regulation

The noradrenergic nucleus locus coeruleus (LC) has been reported to regulate luteinising hormone (LH) secretion in female rats. Both oestrogen and progestin receptors have been demonstrated in LC neurones, suggesting that these cells are possibly responsive to variations in circulating levels of ovarian steroids. We therefore evaluated changes in the activity of LC neurones during the oestrous cycle and after ovarian-steroid treatment in ovariectomised (OVX) rats, as determined by immunoreactivity to Fos-related antigens (FRA), which comprises all of the known members of the Fos family. Effects of ovarian steroids on the firing rate of LC neurones were also determined in a slice preparation. The number of FRA/tyrosine hydroxylase (TH)-immunoreactive (ir) neurones in the LC increased from 14.00-16.00 h on pro-oestrus, coinciding with the onset of the LH surge and rise in plasma progesterone. FRA immunoreactivity was unaltered during dioestrus. Oestradiol-treated OVX rats (OVX+E) displayed marked reduction in FRA/TH-ir neurones in LC compared to oil-treated OVX rats. Accordingly, oestradiol superfusion significantly reduced the spontaneous firing rate of LC neurones in slices from OVX rats. Compared to OVX+E, oestradiol-treated rats injected with progesterone at 08.00 h (OVX+EP) exhibited higher number of FRA/TH-ir neurones in the LC at 10.00 h and 16.00 h, and great amplification of the LH surge. Bath application of progesterone significantly increased the spontaneous firing rate of OVX+E LC neurones. Our data suggest that ovarian steroids may physiologically modulate the activity of LC neurones in females, with possible implications for LH secretion. Moreover, oestradiol and progesterone appear to exert opposite and complementary effects (i.e. whereas oestradiol inhibits, progesterone, after oestradiol priming, stimulates LC activity).

Consumption of a Flaxseed-Rich Food Is Not More Effective Than a Placebo in Alleviating the Climacteric Symptoms of Postmenopausal Women

Our objective in this work was to test the effects of daily intake of bread produced with partially defatted ground flaxseed on the climacteric symptoms and endometrial thickness of postmenopausal women. A double-blind, placebo-controlled, randomized clinical trial was performed with 38 women who had been postmenopausal for 1-10 y and consumed 2 slices of bread containing 25 g of flaxseed (46 mg lignans) or wheat bran (<1 mg lignans; control) every day for 12 consecutive weeks. The outcome variables were the daily number of hot flashes, the Kupperman Menopausal Index (KMI), and endometrial thickness. The plasma lipid profile (total cholesterol and HDL, LDL, and VLDL cholesterol fractions and triglycerides) and the hormones estradiol, follicle-stimulating hormone, thyroid-stimulating hormone, and free thyroxine also were measured. Food intake was evaluated by means of 2 24-hrecalls, before and after the treatment. Twenty patients in the study group and 18 in the control group completed the study. The general characteristics did not differ between the 2 groups at the start of the study. Both had significant, but similar, reductions in hot flashes and KMI after 3 mo of treatment. Moreover, endometrial thickness was not affected in either group. Our findings clearly show that although flaxseed is safe, its consumption at this level (46 mg lignans/d) is no more effective than placebo for reducing hot flashes and KMI. J. Nutr. 140: 293-297, 2010.

Natural antimicrobial ingredients incorporated in biodegradable films based on cassava starch

Biodegradable films based on cassava starch and with addition of natural antimicrobial ingredients were prepared using the casting technique. The tensile properties tensile strength (TS) [MPa] and percent elongation (E) at break [%] and the water vapor transmission (WVT) of the biodegradable films were evaluated and compared with the control (without antimicrobial ingredients). The evaluation of the Colony Forming Units per gram [CFU/g] of pan bread slices packed with the best biodegradable films, in terms of packaging performance, was also determined. The addition onto the matrix of only clove and cinnamon powders could reduce the films WVT when compared to the control, however TS and E were lower than the control and the effect of cinnamon was milder regarding this property. Since water activity of the pan bread slices packed with the biodegradable films increased considerably during the storage period, the antimicrobial effect could not be clearly determined. (C) 2010 Published by Elsevier Ltd.

A Substrate Trapping Mutant Form of Striatal-Enriched Protein Tyrosine Phosphatase Prevents Amphetamine-Induced Stereotypies and Long-Term Potentiation in the Striatum

Background: Chronic, intermittent exposure to psychostimulant drugs results in striatal neuroadaptations leading to an increase in an array of behavioral responses on subsequent challenge days. A brain-specific striatal-enriched tyrosine phosphatase (STEP) regulates synaptic strengthening by dephosphorylating and inactivating several key synaptic proteins. This study tests the hypothesis that a substrate-trapping form of STEP will prevent the development of amphetamine-induced stereotypies. Methods: A substrate-trapping STEP protein, TAT-STEP (C-S), was infused into the ventrolateral striatum on each of 5 consecutive exposure days and I hour before amphetamine injection. Animals were challenged to see whether sensitization to the stereotypy-producing effects of amphetamine developed. The same TAT-STEP (C-S) protein was used on acute striatal slices to determine the impact on long-term potentiation and depression. Results: Infusion of TAT-STEP (C-S) blocks the increase of amphetamine-induced stereotypies when given during the 5-day period of sensitization. The TAT-STEP (C-S) has no effect if only infused on the challenge day. Treatment of acute striatal slices with TAT-STEP (C-S) blocks the induction of long-term potentiation and potentates long-term depression. Conclusions: A substrate trapping form of STEP blocks the induction of amphetamine-induced neuroplasticity within the ventrolateral striatum and supports the hypothesis that STEP functions as a tonic break on synaptic strengthening.

Anesthetic Activation of Central Respiratory Chemoreceptor Neurons Involves Inhibition of a THIK-1-Like Background K(+) Current

At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.

Slicing the metric space to provide quick indexing of complex data in the main memory

Searching in a dataset for elements that are similar to a given query element is a core problem in applications that manage complex data, and has been aided by metric access methods (MAMs). A growing number of applications require indices that must be built faster and repeatedly, also providing faster response for similarity queries. The increase in the main memory capacity and its lowering costs also motivate using memory-based MAMs. In this paper. we propose the Onion-tree, a new and robust dynamic memory-based MAM that slices the metric space into disjoint subspaces to provide quick indexing of complex data. It introduces three major characteristics: (i) a partitioning method that controls the number of disjoint subspaces generated at each node; (ii) a replacement technique that can change the leaf node pivots in insertion operations; and (iii) range and k-NN extended query algorithms to support the new partitioning method, including a new visit order of the subspaces in k-NN queries. Performance tests with both real-world and synthetic datasets showed that the Onion-tree is very compact. Comparisons of the Onion-tree with the MM-tree and a memory-based version of the Slim-tree showed that the Onion-tree was always faster to build the index. The experiments also showed that the Onion-tree significantly improved range and k-NN query processing performance and was the most efficient MAM, followed by the MM-tree, which in turn outperformed the Slim-tree in almost all the tests. (C) 2010 Elsevier B.V. All rights reserved.

Non-homogeneous liver distribution of photosensitizer and its consequence for photodynamic therapy outcome

Background: Photodynamic therapy is mainly used for treatment of malignant lesions, and is based on selective location of a photosensitizer in the tumor tissue, followed by light at wavelengths matching the photosensitizer absorption spectrum. In molecular oxygen presence, reactive oxygen species are generated, inducing cells to die. One of the limitations of photodynamic therapy is the variability of photosensitizer concentration observed in systemically photosensitized tissues, mainly due to differences of the tissue architecture, cell lines, and pharmacokinetics. This study aim was to demonstrate the spatial distribution of a hematoporphyrin derivative, Photogem(R), in the healthy liver tissue of Wistar rats via fluorescence spectroscopy, and to understand its implications on photodynamic response. Methods: Fifteen male Wistar rats were intravenously photosensitized with 1.5 mg/kg body weight of Photogem(R). Laser-induced fluorescence spectroscopy at 532nm-excitation was performed on ex vivo liver slices. The influence of photosensitizer surface distribution detected by fluorescence and the induced depth of necrosis were investigated in five animals. Results: Photosensitizer distribution on rat liver showed to be greatly non-homogeneous. This may affect photodynamic therapy response as shown in the results of depth of necrosis. Conclusions: As a consequence of these results, this study suggests that photosensitizer surface spatial distribution should be taken into account in photodynamic therapy dosimetry, as this will help to better predict clinical results. (C) 2010 Elsevier B.V. All rights reserved.

The Guarguaraz Complex and the Neoproterozoic-Cambrian evolution of southwestern Gondwana: Geochemical signatures and geochronological constraints

The Guarguaraz Complex, in western Argentina, comprises a metasedimentary assemblage, associated with mafic sills and ultramafic bodies intruded by basaltic dikes, which are interpreted as Ordovician dismembered ophiolites. Two kinds of dikes are recognized, a group associated with the metasediments and the other ophiolite-related. Both have N-MORB signatures, with epsilon(Nd) between +3.5 and +8.2, indicating a depleted source, and Grenville model ages between 0.99 and 1.62 Ga. A whole-rock Sm-Nd isochron yielded an age of 655 +/- 76 Ma for these mafic rocks, which is compatible with cianobacteria and acritarchae recognized in the clastic metasedimentary platform sequences, that indicate a Neoproterozoic (Vendian)-Cambrian age of deposition. The Guarguaraz metasedimentary-ophiolitic complex represents, therefore, a remnant of an oceanic basin developed to the west of the Grenville-aged Cuyania terrane during the Neoproterozoic. The southernmost extension of these metasedimentary sequences in Cordon del Portillo might represent part of this platform and not fragments of the Chilenia terrane. An extensional event related to the fragmentation of Rodinia is represented by the mafic and ultramafic rocks. The Devonian docking of Chilenia emplaced remnants of ocean floor and slices of the Cuyania terrane (Las Yaretas Gneisses) in tectonic contact with the Neoproterozoic metasediments, marking the Devonian western border of Gondwana. (C) 2009 Elsevier Ltd. All rights reserved.

Tectonic implications of a paleomagnetic study of the Sarmiento Ophiolitic Complex, southern Chile

A paleomagnetic study was carried out on the Late Jurassic Sarmiento Ophiolitic Complex (SOC) exposed in the Magallanes fold and thrust belt in the southern Patagonian Andes (southern Chile). This complex, mainly consisting of a thick succession of pillow-lavas, sheeted dikes and gabbros, is a seafloor remnant of the Late Jurassic to Early Cretaceous Rocas Verdes basin that developed along the south-western margin of South America. Stepwise thermal and alternating field demagnetization permitted the isolation of a post-folding characteristic remanence, apparently carried by fine grain (SD?) magnetite, both in the pillow-lavas and dikes. The mean ""in situ"" direction for the SOC is Dec: 286.9 degrees, Inc: -58.5 degrees, alpha-95: 6.9 degrees, N: 11 (sites). Rock magnetic properties, petrography and whole-rock K-Ar ages in the same rocks are interpreted as evidence of correlation between remanence acquisition and a greenschist facies metamorphic overprint that must have occurred during latest stages or after closure and tectonic inversion of the basin in the Late Cretaceous. The mean remanence direction is anomalous relative to the expected Late Cretaceous direction from stable South America. Particularly, a declination anomaly over 50 degrees is suggestively similar to paleomagnetically interpreted counter clockwise rotations found in thrust slices of the Jurassic El Quemado Fm. located over 100 km north of the study area in Argentina. Nevertheless, a significant ccw rotation of the whole SOC is difficult to reconcile with geologic evidence and paleogeographic models that suggest a narrow back-arc basin sub-parallel to the continental margin. A rigid-body 30 degrees westward tilting of the SOC block around a horizontal axis trending NNW, is considered a much simpler explanation, being consistent with geologic evidence. This may have occurred as a consequence of inverse reactivation of old normal faults, which limit both the SOC exposures and the Cordillera Sarmiento to the East. The age of tilting is unknown but it must postdate remanence acquisition in the Late Cretaceous. Two major orogenic events of the southern Patagonian Andes, in the Eocene (ca. 42 Ma) and Middle Miocene (ca. 12 Ma), respectively, could have caused the proposed tilting. (C) 2008 Elsevier B.V. All rights reserved.

Geology and geochronology of the Betara region in south-southeastern Brazil: Evidence for possible Statherian (1.80-1.75 Ga) and Calymmian (1.50-1.45 Ga) extension events

The results of geological mapping, chemical analysis and radiometric dating of metabasic rocks of Betara Formation, and mapping and dating of those present in the Betara basement nucleus together with mylonitic granodiorite and syenogranite are reported here. U-Pb analysis of bulk zircon fractions from the metabasic rocks of the basement nucleus yielded a Statherian age of 1790 +/- 22 Ma, while the metabasic rocks from the upper part of the Betara Formation yielded a Calymmian age between 1500 and 1450 Ma. This age is a minimum for the deposition of the Betara Formation. The older metabasic rocks are associated with post-tectonic, possibly anorogenic syenogranite, while the younger ones are gabbro or very porphyritic ankaramite whose REE patterns are consistent with crystallization from an N-MORB parent magma. The observations and data point to the probable events associated with extensional processes of the end of Paleoproterozoic and early Mesoproterozoic. Similar registers of Statherian (1.80-1.75 Ga) and Calymmian (1.50-1.45 Ga) extensional events are recorded in other parts of the South American and African continents. The Neoproterozoic witnessed the formation and junction of the tectonic slices which formed the Apiai domain during the assemblage of western Gondwana. (C) 2010 International Association for Gondwana Research. Published by Elsevier B.V. All rights reserved.

The Gelfand-Kirillov conjecture and Gelfand-Tsetlin modules for finite W-algebras

We address two problems with the structure and representation theory of finite W-algebras associated with general linear Lie algebras. Finite W-algebras can be defined using either Kostant`s Whittaker modules or a quantum Hamiltonian reduction. Our first main result is a proof of the Gelfand-Kirillov conjecture for the skew fields of fractions of finite W-algebras. The second main result is a parameterization of finite families of irreducible Gelfand-Tsetlin modules using Gelfand-Tsetlin subalgebra. As a corollary, we obtain a complete classification of generic irreducible Gelfand-Tsetlin modules for finite W-algebras. (C) 2009 Elsevier Inc. All rights reserved.

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display important biological effects, many of them mediated by nicotinic receptors. Cembranoids from tobacco are neuroprotective through a nicotinic anti-apoptotic mechanism preventing excitotoxic neuronal death which in part could result from anti-inflammatory properties of cembranoids. Moreover, tobacco cembranoids also have anti-inflammatory properties which could enhance their neuroprotective properties. Cembranoids from tobacco affect nicotine-related behavior: they increase the transient initial ataxia caused by first nicotine injection into naive rats and inhibit the expression of locomotor sensitization to repeated injections of nicotine. In addition, cembranoids are known to act as anti-tumor compounds. In conclusion, cembranoids provide a promising source of lead drugs for many clinical areas, including neuroprotection, smoking-cessation, and anti-cancer therapies. (C) 2009 Elsevier Ltd. All rights reserved.