Assembly of the human neutrophil NADPH oxidase involves binding of p67phox and flavocytochrome b to a common functional domain in p47phox

The human neutrophil NADPH oxidase is a multi-component complex composed of membrane-bound and cytosolic proteins. During activation, cytosolic proteins p47(phox), p67(phox), Rac2, and possibly p40(phox) translocate to the plasma membrane and associate with flavocytochrome b to form the active superoxide-generating system. To further investigate the role of p67(phox) in this complex assembly process, experiments were performed to identify possible regions of interaction between p67(phox) and other NADPH oxidase proteins. Using random sequence peptide phage-display library analysis of p67(phox), we identified a novel region in p47(phox) encompassing residues 323-332 and a previously identified SH3 binding domain encompassing p47(phox) residues 361-370 as p67(phox) binding sites. Synthetic peptides mimicking p47(phox) residues 323-332 inhibited the p47(phox)-p67(phox) binding interaction in an affinity binding assay; however, peptides mimicking flanking regions were inactive. Surprisingly, this same region of p47(phox) was found previously to represent a site of binding interaction for flavocytochrome b (DeLeo, F. R., Nauseef, W. M., Jesaitis, A. J., Burritt, J. B., Clark, R. A., and Quinn, M. T.(1995) J. Biol. Chem. 270, 26246-26251), and this observation was confirmed in the present report using two different in vitro assays that were not evaluated previously. Using affinity binding assays, we also found that p67(phox) and flavocytochrome b competed for binding to p47(phox)after activation, suggesting that prior to full NADPH oxidase assembly the 323-332 region of p47(phox) is associated with p67(phox) and at some point in the activation process is transferred to flavocytochrome b. Thus, taken together our data demonstrate that both p67(phox) and flavocytochrome b utilize a common binding site in p47(phox), presumably at distinct stages during the activation process, and this p47(phox) region plays a key role in regulating NADPH oxidase assembly.     

Interacting effects of cognitive load and adult age on the regularity of whole-body motion during treadmill walking.

We investigated effects of concurrent cognitive task difficulty (n-back) on the regularity of whole-body movements during treadmill walking in women and men from 3 age groups (20–30, 60–70, and 70–80 years old). Using principal component analysis of individual gait patterns, we separated main (regular) from residual (irregular) components of whole-body motion. Proportion of residual variance (RV) was used as an index of gait irregularity. The gait in all age groups became more regular (reduced RV) upon introduction of a simple cognitive task (1-back), relative to walking without a concurrent cognitive task. In contrast, parametrically increasing working memory load from 1-back to 4-back led to age-differential effects, with gait patterns becoming more regular in those 20–30 years old, becoming less regular in those 70–80 years old, and showing no significant effects in those 60–70 years old. Our results support the dual-process account of sensorimotor–cognitive interactions (O. Huxhold, S.-C. Li, F. Schmiedek, and U. Lindenberger, 2006), with age-general effects of internal versus external attentional focus and age-specific effects of resource competition with increasing cognitive task difficulty. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Environmental topography and postural control demands shape aging-associated decrements in spatial navigation performance.

This study tests the hypothesis that aging-induced cognitive permeation of sensorimotor functions contributes to adult age differences in spatial navigation performance. Virtual maze-like museums were projected in front of a treadmill. Sixteen 20-30-year-old men and sixteen 60-70-year-old men performed a way-finding task in city-block or variable topographies while walking with or without support. Walking support attenuated age-related decrements in navigational learning. Navigation load increased trunk-angle variability for older adults only. Age differences in spatial knowledge persisted despite perfect place-finding performance. City-block topography was easier than variable topography for younger adults only, indicating age-related differences in reliance on spatial relational learning. Attempts at supporting older adults' navigation performance should consider sensorimotor/cognitive interactions and qualitative differences in navigational activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age differences in processing fluctuations in postural control across trials and across days.

Postural control performances of 18 younger and 18 older adults were repeatedly measured on 45 weekdays with five trials per day. This design made it possible to dissociate between long-term trends and processing fluctuations in the sensorimotor domain at moment-to-moment, trial-to-trial, and day-to-day levels. Older adults fluctuated more than younger adults at all timescales. Age differences in trial-to-trial and day-to-day processing fluctuations were reduced but remained statistically significant when controlling for fluctuations on faster timescales. We concluded that age differences in intraindividual fluctuations at the longer timescales are in part related to age differences in low-level system robustness, suggesting a cascade of effects across multiple timescales. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Is seeking bad mood cognitively demanding? Contra-hedonic orientation and working-memory capacity in everyday life.

Hedonism, or wanting to feel good, is central to human motivation. At times, however, people also seek to maintain or enhance negative affect or to dampen positive affect, and this can be instrumental for the later attainment of their goals. Here, we investigate the assumption that such contra-hedonic orientation is cognitively more demanding than prohedonic orientation, above and beyond the effects of momentary affective experience. We provided 378 participants with mobile phones that they carried with them for 3 weeks while pursuing their daily routines. The phones prompted participants at least 54 times to report their current affect-regulation orientation and to work on two trials of a cognitively demanding working memory task. As expected, contra-hedonic orientation was substantially less prevalent than prohedonic orientation. It was reported in 15% of the measurement occasions. Participants who reported on average more contra-hedonic orientation showed lower average working memory performance throughout the study interval. Further, controlling for the effects of accompanying affective experiences, momentary occurrences of contra-hedonic orientation were associated with temporary declines in working memory performance within individuals, and this could neither be explained by lacking task compliance nor by other characteristics of the individual or the situation. Prohedonic orientation showed a considerably smaller association with working memory performance. These findings are consistent with the view that contra-hedonic orientation is accompanied by momentarily more diminished cognitive resources than is prohedonic orientation. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Developmental change and intraindividual variability: Relating cognitive aging to cognitive plasticity, cardiovascular lability, and emotional diversity.

Repeated assessments obtained over years can be used to measure individuals' developmental change, whereas repeated assessments obtained over a few weeks can be used to measure individuals' dynamic characteristics. Using data from a burst of measurement embedded in the Berlin Aging Study (BASE; Baltes & Mayer, 1999), we illustrate and examine how long-term changes in cognitive ability are related to short-term changes in cognitive performance, cardiovascular function, and emotional experience. Our findings suggest that “better” cognitive aging over approximately 13 years was associated with greater cognitive plasticity, less cardiovascular lability, and less emotional diversity over approximately 2 weeks at age 90 years. The study highlights the potential benefits of multi-time scale longitudinal designs for the study of individual function and development. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The strong connection between sensory and cognitive performance in old age: Not due to sensory acuity reductions operating during cognitive assessment.

Cognitive aging research has documented a strong increase in the covariation between sensory and cognitive functioning with advancing age. In part, this finding may reflect sensory acuity reductions operating during cognitive assessment. To examine this possibility, the authors administered cognitive tasks used in prior studies (e.g., Lindenberger & Baltes, 1994) to middle-aged adults under age-simulation conditions of reduced visual acuity, auditory acuity, or both. Visual acuity was lowered through partial occlusion filters, and auditory acuity through headphone-shaped noise protectors. Acuity manipulations reduced visual acuity and auditory acuity in the speech range to values reaching or approximating old-age acuity levels, respectively, but did not lower cognitive performance relative to control conditions. Results speak against assessment-related sensory acuity accounts of the age-related increase in the connection between sensory and cognitive functioning and underscore the need to explore alternative explanations, including a focus on general aspects of brain aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling intrusions and correct recall in episodic memory: Adult age differences in encoding of list context.

A model for correct recall and intrusions in cued recall of word lists is introduced. Intrusions are false responses that were correct in an earlier list. The model assumes 3 exclusive states for memory traces after encoding: with a list tag (i.e., with information about list origin), without list tags, and missing. Across lists, a trace can lose its list tag or its content. For retrieval, an optimal strategy of response selection was assumed. Younger and older laboratory-trained mnemonists participated in 2 experiments in which recall of permutations of a single word list across a single set of cues was held constant with individually adjusted presentation times. With correct recall equated to younger adults, older adults were more susceptible to intrusions. Age differences were restricted to model parameters estimating the probability of generation of list tags. Alternative accounts of age differences in context memory are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)