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Although neurotrophins have traditionally been regarded as neuronal survival factors, recent work has suggested a role for these factors in synaptic plasticity. In particular, brain-derived neurotrophic factor (BDNF) rapidly enhances synaptic transmission in hippocampal neurons through trkB receptor stimulation and postsynaptic phosphorylation mechanisms. Activation of trkB also modulates hippocampal long-term potentiation, in which postsynaptic N-methyl-D-aspartate glutamate receptors play a key role. However, the final common pathway through which BDNF increases postsynaptic responsiveness is unknown. We now report that BDNF, within 5 min of exposure, elicits a dosedependent increase in phosphorylation of the N-methyl-Daspartate receptor subunit 1. This acute effect occurred in hippocampal synaptoneurosomes, which contain pre-and postsynaptic elements, and in isolated hippocampal postsynaptic densities. Nerve growth factor, in contrast, caused no enhancement of phosphorylation. These results suggest a potential mechanism for trophin-induced potentiation of synaptic transmission.Neurotrophins play important roles in the survival and differentiation of specific neuronal populations during development and adulthood (1-3). Four members of the mammalian neurotrophin gene family have been identified: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4͞5 (4, 5). The neurotrophins bind to receptor tyrosine kinases of the trk protooncogene family with high affinity. trkA is a high-affinity receptor for NGF (6, 7), trkB for BDNF and NT-4͞5 (8, 9) as well as NT-3 (10), and trkC for .In addition to classical trophic activities, we and others have shown that neurotrophins acutely modulate synaptic transmission (12-19) and long-term potentiation (20). Experiments with dissociated cultures of hippocampal neurons indicate that BDNF and NT-4͞5 rapidly and selectively potentiate excitatory synaptic currents (17-19), and this trkB-mediated synaptic enhancement involves phosphorylation-dependent modulation of postsynaptic responsiveness (18). The exact mechanisms by which trkB activation modulates synaptic transmission remain to be established.We recently found that trkB is a functionally active, intrinsic component of the adult rat postsynaptic density (PSD) isolated from cerebral cortex and hippocampus (21). The PSD is a proteinaceous disc-shaped subcellular organelle apposed to the inner surface of the postsynaptic membrane of chemical synapses (22). Neurotransmitter receptors, protein kinases, and ion channel proteins are anchored to the PSD (22), suggesting that the PSD participates in signal transduction and even receptor regulation. In fact, our recent studies revealed that N-methyl-D-aspartate (NMDA) receptors can be phosphorylated by intrinsic PSD kinases (23,24). Phosphorylation of NMDA receptors is known to enhance receptor binding, channel conductance, and synaptic transmission (25-27). Because trkB activation enhances synaptic activity via postsynaptic phosphor...

The swelling of a polymer glass by sorption of a small molecule penetrant is considered in a regime characterized by so-called case-II diffusion. Attention is focused on the polymer so that the swelling process can be investigated apart from diffusion. The model of Thomas and Windle (TW) is used to predict the surface swelling as a function of exposure time. This model assumes that the swelling is driven by the osmotic pressure which relaxes to zero as the surface penetrant volume fraction φs approaches its equilibrium value φe. The rate-controlling factor of the swelling process is the viscosity of the polymer η, which decreases with increasing surface sorption according to η=η0 exp(−mφ) where η0 is the viscosity of the unswollen polymer. For large values of M=mφe, φs is very small until a time τ is reached beyond which the swelling then accelerates rapidly towards its equilibrium value. This feature is absent if M<e. The time τ is estimated by asymptotic analysis. Rutherford backscattering spectrometry is used to investigate the surface swelling kinetics of polystyrene by iodohexane. The TW model tends to underestimate the swelling rate when φs is low and to overestimate it when φs is high. Nevertheless, the time for φs to approach its equilibrium value φe is approximated well by the TW model.

We consider front formation and steady-state front motion in a one-dimensional polymer system undergoing case-II diffusion. The polymer system approximates a polymer sheet whose thickness is very small compared with its lateral dimensions. The osmotic pressure of Thomas and Windle (TW) is used in the theoretical analysis. The transient problem of front formation is formulated. It is found that the original coupled system of partial differential equations proposed by TW can be reduced to one equation. An exact solution of this equation for a diffusion front moving with a velocity V is presented. The solution allows us to predict the dependence of the steady-state velocity on material parameters and the equilibrium concentration of penetrant outside the sheet. The concentration and pressure profile ahead of the moving front is obtained. We also show that the TW Model predicts the existence of a Fickian tail ahead of the steadily moving front. Conditions for the dominance of the Fickian tail are determined. The predicitions of our theoretical analysis are then compared with concentration profiles of iodohexane diffusing into polystyrene determined from Rutherford backscattering spectrometry.

following correction should be noted. Due to an editorial change at PNAS, the meaning of the last sentence on page 14046 was altered. The sentence originally read as follows: On the other hand, this structure does not reproduce the pharmacological properties of either P or Q channel exactly, as the ID 50 to sFTX and -Aga IVA for P-type channels is lower than for the ␣1A, ␣2␦, ␤Ib channels in HEK cells.Neurobiology. In the article "The synthesis of ATP by glycolytic enzymes in the postsynaptic density and the effect of endogenously generated nitric oxide" Kuo Wu, Chiye Aoki, Alice Elste, Adrienne A. Rogalski-Wilk, and Philip Siekevitz, which appeared in number 24, November 25, 1997, of Proc. Natl. Acad. Sci. USA (94,(13273)(13274)(13275)(13276)(13277)(13278), the quality of the reproduction of Fig. 2A was poor. The figure and its legend are shown below:Biochemistry. In the article "KSR stimulates Raf-1 activity in a kinase-independent manner" by Neil R. Michaud, Marc Therrien, Angela Cacace, Lisa C. Edsall, Sarah Spiegel, Gerald M. Rubin, and Deborah K. Morrison, which appeared in number 24, November 25, 1997, of Proc. Natl. Acad. Sci. USA (94,(12792)(12793)(12794)(12795)(12796), the following correction should be noted.Due to a printer's error, background was incorrectly added to (50 g) and 100 g each of the other fractions, in 100 l final volume, including whole homogenate (H), synaptosomes (Syn), synaptic plasma membranes (SPM), and crude synaptic vesicles (CSV), were incubated at 37°C for 15 min. NAD incorporation was performed in the absence (Ϫ) or presence (ϩ) of SNP as exogenous source of NO. The mixtures were subjected to SDS͞PAGE and then autoradiography. (B) Western blot analysis of the G3PD in the subcellular fractions. To confirm that the radioactive protein in the subcellular fractions was indeed G3PD, Western blot analysis was performed by using specific anti-G3PD antibodies as described.

This paper reports solutions to the issues of profile control, microloading effect and suppression of the sidewall roughness of submicrometer trenches by modifying the regular conditions of the Bosch process that is often employed in the inductively coupled plasma (ICP) deep reactive ion etching (DRIE) system. Additionally, under the modified processing conditions, a high efficient antireflection structure can be fabricated.

Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease. Moderate cognitive airment is a feature of DMD, but the underlying mecaisms are unknown. DMD is cra d by a defect in a protein,, dystrophin, that is located pdominamtly in muscle but has been dtecled in brain. We sought to dlrectiy localize dystophn within the complex synaptic structure of the cerebral cortex by fin on the postsynaptic density (PSD), which appears to be central to Fyaplcfamction.We report that a specific anti-dystrophin antibody (anti 6-10) recognizes three distinct proteins In the purified PSD: the 400-kDa dystrophin and two previously u fied dystrophin-related proteins of 120 and 110 kDa. These proteins exhibited differential r exprsin in PSDs from cerebral cortex, cerebellum, and olfactory bulb. In the cortical PSD, the 400-kDa dystrophin was predominant, whereas the 120-kDa protein was the major species In cerl and olfactory bulb PSDs. The three proteins were differentially expressed in the PSD during cortical development: the 4W0-kDa protein exhibited a selective 9-fold inase during po days 7 to 10, suggesting a normal physiological role in synaptic maturation. The PSD from the mdx mouse, a model of human DMD, contained no detctable 400-kDa dystrophin but expressed the two dphin-related proteins. Our results indicate that brain dystrophins are laled to the PSD, potentially as three isoforms, and raise the possibility that cognitive abnormalities in DMD are attributable to synaptic dy on associated with deficits in brain dystopin molecules.Duchenne muscular dystrophy (DMD) is a common, lethal, chromosome X-linked inherited disease affecting 1 in 3500 boys (for review, see ref.

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