Amygdala functional connectivity with medial prefrontal cortex at rest predicts the positivity effect in older adults’ memory

As people get older, they tend to remember more positive than negative information. This age-by-valence interaction has been called “positivity effect.” The current study addressed the hypotheses that baseline functional connectivity at rest is predictive of older adults' brain activity when learning emotional information and their positivity effect in memory. Using fMRI, we examined the relationship among resting-state functional connectivity, subsequent brain activity when learning emotional faces, and individual differences in the positivity effect (the relative tendency to remember faces expressing positive vs. negative emotions). Consistent with our hypothesis, older adults with a stronger positivity effect had increased functional coupling between amygdala and medial PFC (MPFC) during rest. In contrast, younger adults did not show the association between resting connectivity and memory positivity. A similar age-by-memory positivity interaction was also found when learning emotional faces. That is, memory positivity in older adults was associated with (a) enhanced MPFC activity when learning emotional faces and (b) increased negative functional coupling between amygdala and MPFC when learning negative faces. In contrast, memory positivity in younger adults was related to neither enhanced MPFC activity to emotional faces, nor MPFC–amygdala connectivity to negative faces. Furthermore, stronger MPFC–amygdala connectivity during rest was predictive of subsequent greater MPFC activity when learning emotional faces. Thus, emotion–memory interaction in older adults depends not only on the task-related brain activity but also on the baseline functional connectivity.

Control of human immunodeficiency virus type-1 protease activity in insect cells expressing Gag-Pol rescues assembly of immature but not mature virus-like particles

Expression of human immunodeficiency virus type 1 (HIV-1) Gag protein in insect cells using baculovirus vectors leads to the abundant production of virus-like particles (VLPs) that represent the immature form of the virus. When Gag-Pol is included, however, VLP production is abolished, a result attributed to premature protease activation degrading the intracellular pool of Gag precursor before particle assembly can occur. As large-scale synthesis of mature noninfectious VLPs would be useful, we have sought to control HIV protease activity in insect cells to give a balance of Gag and Gag-Pol that is compatible with mature particle formation. We show here that intermediate levels of protease activity in insect cells can be attained through site-directed mutagenesis of the protease and through antiprotease drug treatment. However, despite Gag cleavage patterns that mimicked those seen in mammalian cells, VLP synthesis exhibited an essentially all-or-none response in which VLP synthesis occurred but was immature or failed completely. Our data are consistent with a requirement for specific cellular factors in addition to the correct ratio of Gag and Gag-Pol for assembly of mature retrovirus particles in heterologous cell types. (C) 2003 Elsevier Science (USA). All rights reserved.

Expressing medicine side effects: assessing the effectiveness of absolute risk, relative risk, and number needed to harm, and the provision of baseline risk information

Objective: To assess the effectiveness of absolute risk, relative risk, and number needed to harm formats for medicine side effects, with and without the provision of baseline risk information. Methods: A two factor, risk increase format (relative, absolute and NNH) x baseline (present/absent) between participants design was used. A sample of 268 women was given a scenario about increase in side effect risk with third generation oral contraceptives, and were required to answer written questions to assess their understanding, satisfaction, and likelihood of continuing to take the drug. Results: Provision of baseline information significantly improved risk estimates and increased satisfaction, although the estimates were still considerably higher than the actual risk. No differences between presentation formats were observed when baseline information was presented. Without baseline information, absolute risk led to the most accurate performance. Conclusion: The findings support the importance of informing people about baseline level of risk when describing risk increases. In contrast, they offer no support for using number needed to harm. Practice implications: Health professionals should provide baseline risk information when presenting information about risk increases or decreases. More research is needed before numbers needed to harm (or treat) should be given to members of the general populations. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Substance P released by TRPV1-expressing neurons produces reactive oxygen species that mediate ethanol-induced gastric injury

Although neurokinin 1 receptor antagonists prevent ethanol (EtOH)-induced gastric lesions, the mechanisms by which EtOH releases substance P (SP) and SP damages the mucosa are unknown. We hypothesized that EtOH activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to release SP, which stimulates epithelial neurokinin 1 receptors to generate damaging reactive oxygen species (ROS). SP release was assayed in the mouse stomach, ROS were detected using dichlorofluorescein diacetate, and neurokinin 1 receptors were localized by immunofluorescence. EtOH-induced SP release was prevented by TRPV1 antagonism. High dose EtOH caused lesions, and TRPV1 or neurokinin 1 receptor antagonism and neurokinin 1 receptor deletion inhibited lesion formation. Coadministration of low, innocuous doses of EtOH and SP caused lesions by a TRPV1-independent but neurokinin 1 receptor-dependent process. EtOH, capsaicin, and SP stimulated generation of ROS by superficial gastric epithelial cells expressing neurokinin 1 receptors by a neurokinin 1 receptor-dependent mechanism. ROS scavengers prevented lesions induced by a high EtOH dose or a low EtOH dose plus SP. Gastric lesions are caused by an initial detrimental effect of EtOH, which is damaging only if associated with TRPV1 activation, SP release from sensory nerves, stimulation of neurokinin 1 receptors on epithelial cells, and ROS generation.

Claviceps purpurea expressing polygalacturonases escaping PGIP inhibition fully infects PvPGIP2 wheat transgenic plants but its infection is delayed in wheat transgenic plants with increased level of pectin methyl esterification

Claviceps purpurea is a biotrophic fungal pathogen of grasses causing the ergot disease. The infection process of C. purpurea on rye flowers is accompanied by pectin degradation and polygalacturonase (PG) activity represents a pathogenicity factor. Wheat is also infected by C. purpurea and we tested whether the presence of polygalacturonase inhibiting protein (PGIP) can affect pathogen infection and ergot disease development. Wheat transgenic plants expressing the bean PvPGIP2 did not show a clear reduction of disease symptoms when infected with C. purpurea. To ascertain the possible cause underlying this lack of improved resistance of PvPGIP2 plants, we expressed both polygalacturonases present in the C. purpurea genome, cppg1 and cppg2 in Pichia pastoris. In vitro assays using the heterologous expressed PGs and PvPGIP2 showed that neither PG is inhibited by this inhibitor. To further investigate the role of PG in the C. purpurea/wheat system, we demonstrated that the activity of both PGs of C. purpurea is reduced on highly methyl esterified pectin. Finally, we showed that this reduction in PG activity is relevant in planta, by inoculating with C. purpurea transgenic wheat plants overexpressing a pectin methyl esterase inhibitor (PMEI) and showing a high degree of pectin methyl esterification. We observed reduced disease symptoms in the transgenic line compared with null controls. Together, these results highlight the importance of pectin degradation for ergot disease development in wheat and sustain the notion that inhibition of pectin degradation may represent a possible route to control of ergot in cereals.

Thinking about a limited future enhances the positivity of younger and older adults’ recall: support for socioemotional selectivity theory

Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants’ recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults’ recall is typically more positive than younger adults’ recall may index naturally shifting time horizons and goals with age.