פרסומים

Cocaine-induced long-term potentiation of glutamatergic synapses in the ventral tegmental area (VTA) has been proposed as a key process that contributes to the development of addictive behaviors. In particular, the activation of ionotrophic glutamate NMDA receptor (NMDAR) in the VTA is critical for the initiation of cocaine sensitization. Here we show that application of cocaine both in slices and in vivo induced an increase in tyrosine phosphorylation of the NR2A, but not the NR2B subunit of the NMDAR in juvenile rats. Cocaine induced an increase in the activity of both Fyn and Src kinases, and the Src-protein tyrosine kinase (Src-PTKs) inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), abolished both cocaine-induced increase in tyrosine phosphorylation of the NR2A subunit and the increase in the expression of NR1, NR2A, and NR2B in the VTA. Moreover, cocaine-induced enhancement in NMDAR-mediated excitatory post-synaptic currents was completely abolished by PP2. Taken together, these results suggest that acute cocaine induced an increase in the expression of NMDAR subunits and enhanced tyrosine phosphorylation of NR2A-containing NMDAR through members of the Src-PTKs. This in turn, increased NMDAR-mediated currents in VTA dopamine neurons. These results provide a potential cellular mechanism by which cocaine triggers NMDAR-dependent synaptic plasticity of VTA neurons that may underlie the development of behavioral sensitization.

Two-player zero-sum stochastic games with finite state and action spaces, as well as two-player zero-sum absorbing games with compact metric action spaces, are known to have undiscounted values. We study such games under the assumption that one or both players observe the actions of their opponent after some time-dependent delay. We develop criteria for the rate of growth of the delay such that a player subject to such an information lag can still guarantee himself in the undiscounted game as much as he could have with perfect monitoring. We also demonstrate that the player in the Big Match with the absorbing action subject to information lags which grow too rapidly, according to certain criteria, will not be able to guarantee as much as he could have in the game with perfect monitoring. toring.

It is generally assumed that everything that can be said about dependence with the notion of strong global supervenience can also be said with the notion of strong supervenience. It is argued here, however, that strong global supervenience has a metaphysically distinctive role to play. It is shown that when the relevant sets include relations, strong global supervenience and strong supervenience are distinct. It is then concluded that there are claims about dependence of relations that can be made with the global notion of strong supervenience but not with the "local" (individual) one.

We investigated the effect of ascorbic acid (AA) cosolubilized with vitamin E (VE) on reverse hexagonal (HII) mesophase. The HII phase comprises monoolein (GMO)/D-$\alpha$-tocopherol (VE) in a ratio of 90/10 by wt. and 12.5 wt% water. The macrostructural characteristics of this system were detd. by polarized light microscopy and small-angle X-ray scattering measurements. We used differential scanning calorimetry and attenuated total reflectance Fourier transform IR to characterize the microstructure, the vibration of the functional groups, and the location of the AA guest mol. AA was incorporated to the system in two steps: 1-4 wt% AA and 5-6 wt% AA. We compared this system to one contg. tricaprylin as the oil phase, as previously reported. These measurements revealed that AA is localized first in the water rich-core and in the interface, and acts as a chaotropic mol. that decreases the water m.p. When a larger quantity of AA (5-6 wt%) is added, the system is satd., and the AA is located in the inner cylinder and manifested by more moderate distortion. The addn. of AA also causes alteration in the behavior of the GMO hydrocarbon chains and makes them more flexible. Further addn. of AA caused the GMO hydrocarbon chain to be more solvated by the VE hydrocarbon chain and enabled addnl. migration of VE; hence a decrease in the hydrophobic melting temp. occurred (similar to tricaprylin). Increasing the amt. of AA weakened the bonding between the GMO and water and created new bonds between AA and GMO and AA with water. [on SciFinder(R)]

The physical and the interfacial properties of pectins de-esterified by a specific block-wise enzymatic procedure were investigated. Two major types of block-wise de-esterified pectins with different internal distribution of carboxylic acid on the pectin chains were explored. Type C and type U pectins with the same degree of methylesterification are different and a more block-wise intramolecular distribution in comparison to commercial native apple pectin. The most ordered pectin (U63 pectin, 63% methyl-esterified pectin) has the highest electrophoretic mobility (zeta-potential). It reveals more pronounced intermolecular interactions since it exhibited, at low pH, the lowest circular dichroism intensity at shorter wavelength. U63 pectin (at acidic pH, without calcium addition) has a higher viscosity and formed a stronger gel compared to the less ordered C63 pectin and/or native apple pectin. X-ray patterns show that powdered U63 pectin is more crystalline than C63 pectin, while apple pectin is mostly amorphous. The modified pectin also, most effectively, reduced the surface tension (55 mN/m) and the interfacial tension (5.6 mN/m), probably due to the preferred surface orientation of the carboxylic groups at the water/air or water/oil interfaces. It was demonstrated that the internal charge distribution within the backbone of the pectin is an effective factor in its crystalline organization and its solution properties. It is, therefore, expected that the U63 pectin will exhibit better emulsification capabilities and will form stronger complexes with proteins. (C) 2008 Elsevier Ltd. All rights reserved.

Human experience takes place in the line of mental time (MT) created through ‘self‐projection’ of oneself to different time‐points in the past or future. Here we manipulated self‐projection in MT not only with respect to one’s life events but also with respect to one’s faces from different past and future time‐points. Behavioural and event‐related functional magnetic resonance imaging activity showed three independent effects characterized by (i) similarity between past recollection and future imagination, (ii) facilitation of judgements related to the future as compared with the past, and (iii) facilitation of judgements related to time‐points distant from the present. These effects were found with respect to faces and events, and also suggest that brain mechanisms of MT are independent of whether actual life episodes have to be re‐experienced or pre‐experienced, recruiting a common cerebral network including the anteromedial temporal, posterior parietal, inferior frontal, temporo‐parietal and insular cortices. These behavioural and neural data suggest that self‐projection in time is a fundamental aspect of MT, relying on neural structures encoding memory, mental imagery and self.

 

SUN-domain proteins interact directly with KASH-domain proteins to form protein complexes that connect the nucleus to every major cytoskeleton network. SUN-KASH protein complexes are also required for attaching centrosomes to the nuclear periphery and for alignment of homologous chromosomes, their pairing and recombination in meiosis. Other functions that require SUN-domain proteins include the regulation of apoptosis and maturation and survival of the germline. Laminopathic diseases affect the distribution of the SUN-KASH complexes, and mutations in KASH-domain proteins can cause Emery Dreifuss muscular dystrophy and recessive cerebellar ataxia. This review describes our current knowledge of the role of SUN-KASH domain protein complexes during development, meiosis and disease.

Nuclear lamins are involved in most nuclear activities and are essential for retaining the mechano-elastic properties of the nucleus. They are nuclear intermediate filament (IF) proteins forming a distinct meshwork-like layer adhering to the inner nuclear membrane, called the nuclear lamina. Here, we present for the first time, the three-dimensional supramolecular organization of lamin 10 nm filaments and paracrystalline fibres. We show that Caenorhabditis elegans nuclear lamin forms 10 nm IF-like filaments, which are distinct from their cytoplasmic counterparts. The IF-like lamin filaments are composed of three and four tetrameric protofilaments, each of which contains two partially staggered anti-parallel head-to-tail polymers. The beaded appearance of the lamin filaments stems from paired globular tail domains, which are spaced regularly, alternating between 21 nm and 27 nm. A mutation in an evolutionarily conserved residue that causes Hutchison-Gilford progeria syndrome in humans alters the supramolecular structure of the lamin filaments. On the basis of our structural analysis, we propose an assembly pathway that yields the observed 10 nm IF-like lamin filaments and paracrystalline fibres. These results serve also as a platform for understanding the effect of laminopathic mutations on lamin supramolecular organization.