Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.     

Molecular dissection of effector cell protease receptor-1 recognition of factor Xa. Assignment of critical residues involved in antibody reactivity and ligand binding

Receptor-mediated assembly of blood proteases on vascular cells maintains the hemostatic balance and initiates intracellular signal transduction. Effector cell protease receptor-1 (EPR-1) is an approximately 62-kDa vascular cell membrane receptor for the clotting protease factor Xa, participating in thrombin formation and lymphocyte activation. Here, recombinant EPR-1 fragments were engineered in the frame of intercellular adhesion molecule-1, transfected in mammalian cells, and analyzed for antibody recognition and ligand binding. Chimeric transfectants containing the EPR-1 sequence Met1-Arg60 bound the immunosuppressive anti-EPR-1 monoclonal antibody (mAb) 2E1. In contrast, transfected cells expressing the EPR-1 sequence Pro120-Ala154 were recognized by the functionally inhibitory anti-EPR-1 mAbs 9D4 and B6, bound 125I-factor Xa in a reaction quantitatively indistinguishable from that of wild-type EPR-1 transfectants, and promoted factor Xa concentration-dependent prothrombin activation in the absence of exogenous factor V/Va. Chimeric transfectants expressing the COOH terminus end of the EPR-1 extracellular domain (Ala157-Glu221) did not bind anti-EPR-1 mAbs and did not associate with factor Xa. Mutagenesis of Asn131 or Lys133 in the EPR-1 ligand recognition domain abolished factor Xa binding by 80 +/- 5.5 and 96 +/- 4%, respectively, while mutation of Lys126, Gly128, Asn129, and Asn134 was without effect. A synthetic peptide duplicating the EPR-1 sequence S123PGKPGNQNSKNEPP137 dose dependently inhibited factor V/Va-independent thrombin generation of resting endothelium (IC50 approximately 1 microM), while the adjacent EPR-1 sequence P136PKK-RERERSSHCYP150 was ineffective. These findings demonstrate that EPR-1 contains two spatially distinct functional domains implicated in lymphocyte activation (Met1-Arg60) or factor Xa binding and prothrombin activation (Pro120-Ala154). These interacting sequences may provide a novel potential target for inhibition of factor Xa-dependent vascular cell responses.     

Effects of fatty acid oxidation on glucose utilization by isolated hepatocytes

We have studied the inhibitory action of long- and short-chain fatty acids on hepatic glucose utilization in hepatocytes isolated from fasted rats. The rates of hepatic glucose phosphorylation and glycolysis were determined from the tritiated products of [2-3H] and [6-3H]glucose metabolism, respectively. The difference between these was taken as an estimate of the 'cycling' between glucose and glucose-6-phosphate. In the presence of 40 mM glucose this cycling was estimated at 0.68 mumol/min/g wet wt. Glucose phosphorylation was unaffected during palmitate and hexanoate oxidation to ketone bodies but glycolysis was inhibited. The rate of glucose cycling was increased during this phase to 1.25 mumol/min/g. Following the complete metabolism of the fatty acids, glycolysis was reinstated and cycling rates returned to control levels. Hepatic glucose cycling appears to be an important component of the glucose/fatty acid cycle.     

The effect of verbal elaborations on memory in young and older adults

The Stein paradigm was used to examine the circumstances under which verbal elaborations enhance memory in young and older adults. Subjects studied target adjectives that were embedded in one of three sentence contexts that varied in elaboration of the subject-adjective relationship: (1) nonelaborated base sentences; (2) base sentences with semantically consistent, but arbitrary verbal, elaborations; and (3) base sentences with explanatory verbal elaborations that clarified the significance of the subject-adjective relationship. The presence of the elaborations was varied at encoding and retrieval, and cued recall of the target adjectives was tested with incidental and intentional learning procedures. In Experiments 1A and 1B, explanatory elaborations at encoding and retrieval yielded the largest memorial facilitation for both young and older adults, and the benefit was comparable for the incidental and intentional learning measures. In Experiment 2, age-related differences in recall were minimal with explanatory elaborations at encoding and retrieval, but larger age differences occurred in the nonelaborated comparison conditions. In Experiment 3, explanatory elaborations present at encoding but not at retrieval enhanced recall when the original Stein stimuli were used, but not with the present stimuli. The implications of these results with regard to the mnemonic efficacy of verbal elaborations for young and older adults are discussed.     

Microsatellite loci for stringless bees

What ethical concerns regarding the application of new antidementia compounds are pertinent to the best interests of patients with Alzheimer's disease and their caregivers? Based on collected preliminary anecdotal accounts, these concerns are important and should be considered carefully by clinicians, researchers, and families.     

A theory of reservation-dwelling American Indian alcohol use risk.

The authors present a theory for understanding risk for problem drinking among reservation-dwelling American Indians. The theory offers an overall framework for understanding the risk process for this group. It considers the distinction between factors that influence mean levels of American Indian problem drinking and factors that influence individual differences in American Indian drinking. It proposes important contextual differences between reservation-dwelling American Indians and Caucasians that may help explain the higher mean levels of American Indian problem drinking. The theory further holds that, within the high mean level of problem drinking characteristic of many American Indian reservations, individual differences in problem drinking can be explained by very similar personality and learning factors as those that influence problem-drinking levels for other ethnic groups. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Describing metal surfaces and nanostructures with orbital-free density functional theory

Orbital-free density functional theory (OF-DFT) can be made to scale linearly with sample size, allowing thousands of atoms to be treated explicitly with quantum mechanics. State-of-the-art kinetic energy density functionals and ion–electron pseudopotentials are used to obtain accurate structural property predictions for nanoparticles, nanowires, extended surfaces, and nanoindentation of simple metals.