Utilization of 1-14C- glucose, 1-14C-acetate and 1-14C-palmitate during lipid synthesis in vitro in the liver and skeletal muscles of pigs at different ontogenic stages

The specific radioactivity of lipids synthesized in the liver and quadriceps muscle of 110-day embryos, and 1-, 30-, 60-, 90-day and 12-month pigs in vitro from [1-14C]acetate, [1-14C] glucose and [1-14C] palmitate was investigated. The lipid synthesis from most of the above compounds in the fetal liver developed at a greater rate and in the fetal skeletal muscles at a smaller rate than in livers and skeletal muscles of newborn piglets. During the first months after birth the lipid synthesis from [1-14C] acetate, [1-14C] glucose and [1-14C] palmitate in the liver increased gradually. At the same time the lipid synthesis in skeletal muscles from [1-14C]glucose and [1-14C]palmitate decreased and from [1-14C] acetate increased. The utilization of the above compounds in the lipid synthesis of the liver and quadriceps muscle of pigs follows the decreasing order: [1-14C] palmitate greater than [1-14C]acetate greater than [1-14C]glucose.     

"Memory and the hippocampus: A synthesis from findings with rats, monkeys, and humans": Correction.

Reports an error in the original article by L. R. Squire (Psychological Review, 1992[Apr], Vol 99[2], 195–231). The caption for Figure 7 was incorrect. The corrected caption is given. (The following abstract of this article originally appeared in record 1992-26428-001.) Considers the role of the hippocampus in memory function. A central thesis involving work with rats, monkeys, and humans (which has sometimes seemed to proceed independently in 3 separate literatures) is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented that proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in the neocortex that together represent a whole memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decision making with the "adaptive toolbox": Influence of environmental structure, intelligence, and working memory load.

In 2 experiments with a total of 220 participants, the tendency to use simple heuristics such as the take the best heuristic in an adaptive manner was investigated. In a simulated stock market paradigm, the payoff structure of environments was varied, favoring either compensatory or noncompensatory decision strategies in terms of expected long-term payoff. In both experiments, the majority of participants were classified as using strategies that were adequate for the environment, supporting the notion of adaptive strategy selection. These strategy shifts were moderated by intelligence, as measured with common tests. Neither an additional learning phase (Experiment 1) nor working memory load or working memory capacity (Experiment 2) had additional effects on strategy selection. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analogs of human plasminogen that are labeled with fluorescence probes at the catalytic site of the zymogen. Preparation, characterization, and interaction with streptokinase

Fluorescent analogs of the proteinase zymogen, plasminogen (Pg), which are specifically inactivated and labeled at the catalytic site have been prepared and characterized as probes of the mechanisms of Pg activation. The active site induced non-proteolytically in Pg by streptokinase (SK) was inactivated stoichiometrically with the thioester peptide chloromethyl ketone. N alpha-[(acetylthio)acetyl]-(D-Phe)-Phe-Arg-CH2Cl; the thiol group generated subsequently on the incorporated inhibitor with NH2OH was quantitatively labeled with the fluorescence probe, 2-((4'-iodoacetamido)anilino)naphthalene-6-sulfonic acid; and the labeled Pg was separated from SK. Cleavage of labeled [Glu]Pg1 by urokinase-type plasminogen activator (uPA) was accompanied by a fluorescence enhancement (delta Fmax/Fo) of 2.0, and formation of 1% plasmin (Pm) activity. Comparison of labeled and native [Glu]Pg1 as uPA substrates showed that activation of labeled [Glu]Pg1 generated [Glu]Pm1 as the major product, while native [Glu]Pg1 was activated at a faster rate and produced [Lys]Pm1 because of concurrent proteolysis by plasmin. When a mixture of labeled and native Pg was activated, to include plasmin-feedback reactions, the zymogens were activated at equivalent rates. The lack of potential proteolytic activity of the Pg derivatives allowed their interactions with SK to be studied under equilibrium binding conditions. SK bound to labeled [Glu]Pg1, and [Lys]Pg1 with dissociation constants of 590 +/- 110 and 110 and 11 +/- 7 nM, and fluorescence enhancements of 3.1 +/- 0.1 and 1.6 +/- 0.1, respectively. Characterization of the interaction of SK with native [Glu]Pg1 by the use of labeled [Glu]Pg1 as a probe indicated a approximately 6-fold higher affinity of SK for the native Pg zymogen compared to the labeled Pg analog. Saturating levels of epsilon-aminocaproic acid reduced the affinity of SK for labeled [Glu]Pg1 by approximately 2-fold and lowered the fluorescence enhancement to 1.8 +/- 0.1, whereas the affinity of SK for labeled [Lys]Pg1 was reduced by approximately 98-fold with little effect on the enhancement. These results demonstrate that occupation of lysine binding sites modulates the affinity of SK for Pg and the changes in the environment of the catalytic site associated with SK-induced conformational activation. Together, these studies show that the labeled Pg derivatives behave as analogs of native Pg which report functionally significant changes in the environment of the catalytic site of the zymogen.     

Developmental change in the acuity of the "number sense": The approximate number system in 3-, 4-, 5-, and 6-year-olds and adults.

Behavioral, neuropsychological, and brain imaging research points to a dedicated system for processing number that is shared across development and across species. This foundational Approximate Number System (ANS) operates over multiple modalities, forming representations of the number of objects, sounds, or events in a scene. This system is imprecise and hence differs from exact counting. Evidence suggests that the resolution of the ANS, as specified by a Weber fraction, increases with age such that adults can discriminate numerosities that infants cannot. However, the Weber fraction has yet to be determined for participants of any age between 9 months and adulthood, leaving its developmental trajectory unclear. Here we identify the Weber fraction of the ANS in 3-, 4-, 5-, and 6-year-old children and in adults. We show that the resolution of this system continues to increase throughout childhood, with adultlike levels of acuity attained surprisingly late in development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of the structure, function, and conformational stability of PorB class 3 protein from Neisseria meningitidis. A porin with unusual physicochemical properties

PorB proteins constitute the vast majority of channels in neisserial outer membranes and can be subdivided within meningococcal strains into two distinct and mutually exclusive families that are designated as class 2 and class 3 proteins. We recently characterized the functional activity and conformational stability of a PorB class 2 protein from Neisseria meningitidis (Minetti, C. A. S. A., Tai, J. Y., Blake, M. S., Pullen, J. K., Liang, S. M., and Remeta, D. P. (1997) J. Biol. Chem. 272, 10710-10720). To evaluate the structure-function relatedness among the PorB proteins, we have employed a combination of electrophoretic and spectroscopic techniques to assess the conformational stability of zwittergent-solubilized class 3 trimers. The functional, physicochemical, and structural properties of the meningococcal class 2 and class 3 proteins are comparable with the notable exception that the latter exhibits a significantly higher susceptibility to SDS. The SDS-induced dissociation and partial unfolding of PorB class 3 is characterized by a single two-state transition with a midpoint at 0.35% SDS. The native trimeric assembly dissociates reversibly, forming partially folded monomers that retain the characteristic beta-sheet content of the transmembrane domain with a concomitant increase in random coil structure arising from unfolding the rigid surface loops. These results provide new insight into the elucidation of porin folding pathways and the factors that govern the overall structural stability of meningococcal proteins.     

The isolation of eukaryotic ribosomal proteins. The purification and characterization of the 40 S ribosomal subunit proteins S2, S3, S4, S5, S6, S7, S8, S9, S13, S23/S24, S27, and S28

The proteins of the small subunit of rat liver ribosomes were separated into five groups by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5 (Collatz, E., Lin, A., St?ffler, G., Tsurugi, K., and Wool, I.G., (1976) J. Biol. Chem. 251, 1808-1816). From the several groups, 12 proteins (S2,S3, S4, S5, S6, S7, S8, S9, S13, S23/S24, S27, and S28) wereisolated by ion exchange chromatography on carboxymethylcellulose, by chromatography on sulfopropyl-Sephadex, and by gel filtration through Sephadex G-75. The amount of protein obtained varied from 1 to 9 mg depending on the number of steps required for the preparation; several proteins had no detectable contamination and the impurities in the others were no greater than 9%. The molecular weight of the proteins was estimated by polyazrylamide gel electrophoresis in sodium dodecyl sulfate; the amino acid composition was determined.     

In vitro cytotoxicity and DNA damage production in Chinese hamster ovary cells and topoisomerase II inhibition by 2-[2''-(dimethylamino)ethyl]-1, 2-dihydro-3H-dibenz[de,h]isoquinoline-1,3-diones with substitutions at the 6 and 7 positions (azonafides)

The p53 tumor suppressor gene encodes a phosphoprotein which when overexpressed can induce growth arrest at the G1 and G2/M phases of the cell cycle, promote differentiation and apoptosis. This paper demonstrates that p53 can associate with trk tyrosine kinase. Expression of a murine temperature-sensitive (ts) p53 mutant in PC12 cells overexpressing trk (a model system to analyse cellular differentiation and signal transduction induced by NGF) induces morphological changes in the absence of NGF stimulation at 32 degrees C but not at 37 degrees C. In cells differentiated by p53, trk, but not EGFr, was hyperphosphorylated on tyrosine. Furthermore trk was not phosphorylated when expressed in Saos-2 cells (human osteosarcoma cells that lack expression of both endogenous trk and p53) at either temperature. However, transfection of ts p53 into these cells induces trk phosphorylation at 32 degrees C in the absence of NGF stimulation. Association of trk and p53 can be detected in NIH3T3 and PC12 cells co-expressing trk and the ts p53 mutant, in NIH3T3 and PC12 cells transfected with trk alone, and in untransfected PC12 cells, showing that overexpressed and/or endogenous trk associates with endogenous, low levels of p53. These data suggest a novel function for p53 which involves the stimulation of signal transduction pathways (mediating morphological properties of cells), possibly through association with and hyperphosphorylation of trk.     

Synthesis of (+)-(1'R,2'S) and (1'S,2'R)-6,11-dimethyl-1,2,3,4,5,6 -hexahydro-3-[[2'-(alkoxycarbonyl)-2'-phenylcyclopropyl]methyl]-2 ,6 -methano-3-benzazocin-8-ol. Comparison of the affinities for sigma 1 and opioid receptors with in the diastereoisomeric MPCB and CCB

The synthesis and the in vitro receptor affinity for sigma 1 and opiod receptors of the two diastereoisomers of (+)-cis-MPCB namely, (+)-cis-(1'S,2'R)-6,11-Dimethyl-1,2,3,4,5,6 -hexahydro-3-[[2'-(methoxycarbonyl)-2'-phenylcyclopropyl]methyl]-2 ,6 -methano-3-benzazocin-8-ol, (1'S,2'R)6a and (+)-cis-(1'R,2'S)-6,11-Dimethyl-1,2,3,4,5,6-hexahydro-3- [[2-(methoxycarbonyl)-2'-phenylcyclopropyl]methyl]-2,6-methano-3-+ ++benzazocin-8 -ol, (1'R,2'S)6a are reported. Affinities of (1'S,2'R)6a and (1'R,2'S)6a were compared with those of the (-)-cis-diastereoisomers of MPCB(1), and of its p-Cl phenyl derivative CCB(2). The (+)-cis-N-normetazocine derivatives showed higher affinity for the sigma 1 sites, labeled with [3H]-(+)-pentazocine than the corresponding (-)-cis- analogs. In particular, compound (1'S,2'R)6a showed a Ki = 66.7 nM for sigma 1 receptor, associated with a good selectivity for sigma 1 with respect to kappa, mu, delta opioid receptors subtypes (Ki = > 1,000 nM). Analysis of the data seem to support the hypothesis that the (+)-cis-N-normetazocine nucleus posses a specific enantioselectivity for sigma 1 sites, when supporting bulkier N-substituents functionalized with a carboxy ester group.