Thermodynamic profile of mutual subunit control in a heteromeric receptor.

Cyclic nucleotide-gated (CNG) ion channels of olfactory neurons are tetrameric membrane receptors that are composed of two A2 subunits, one A4 subunit, and one B1b subunit. Each subunit carries a cyclic nucleotide-binding domain in the carboxyl terminus, and the channels are activated by the binding of cyclic nucleotides. The mechanism of cooperative channel activation is still elusive. Using a complete set of engineered concatenated olfactory CNG channels, with all combinations of disabled binding sites and fit analyses with systems of allosteric models, the thermodynamics of microscopic cooperativity for ligand binding was subunit- and state-specifically quantified. We show, for the closed channel, that preoccupation of each of the single subunits increases the affinity of each other subunit with a Gibbs free energy (ΔΔG) of ∼-3.5 to ∼-5.5 kJ ⋅ mol-1, depending on the subunit type, with the only exception that a preoccupied opposite A2 subunit has no effect on the other A2 subunit. Preoccupation of two neighbor subunits of a given subunit causes the maximum affinity increase with ΔΔG of ∼-9.6 to ∼-9.9 kJ ⋅ mol-1 Surprisingly, triple preoccupation leads to fewer negative ΔΔG values for a given subunit as compared to double preoccupation. Channel opening increases the affinity of all subunits. The equilibrium constants of closed-open isomerizations systematically increase with progressive liganding. This work demonstrates, on the example of the heterotetrameric olfactory CNG channel, a strategy to derive detailed insights into the specific mutual control of the individual subunits in a multisubunit membrane receptor.

Neurocognitive Outcome Following Recovery from Severe Acute Respiratory Syndrome - Coronavirus-1 (SARS-CoV-1).

OBJECTIVE: Severe acute respiratory syndrome (SARS) is a highly contagious viral respiratory illness associated with hypoxia and dyspnea. Many of those who contracted and recovered from SARS during the 2002-2003 outbreak reported persistent physical, psychological, and cognitive difficulties. Here, we investigated the residual influences of SARS on cognition for a subset of healthcare professionals who recovered and were referred for neuropsychological evaluation through their workplace insurance. METHOD: Twenty-eight healthcare professionals were evaluated on neuropsychological and mood functioning approximately 1.5 years post-recovery from a severe respiratory illness. Test scores were compared with age-matched normative data, and correlations were examined between mood, self-report memory scales, subjective complaints (e.g., poor concentration, pain, fatigue), illness severity (i.e., length of hospitalization, oxygen use during hospital stay), and cognitive performance. RESULTS: Participants performed within age expectations on the majority of cognitive measures including overall memory ability. Although processing speed was generally within normal limits, 43% showed significant speed-accuracy trade-offs favoring accuracy over maintaining speed. Deficits were observed on measures of complex attention, such as working memory and the ability to sustain attention under conditions of distraction. Participants endorsed poorer memory ability than same-age peers on a meta-memory measure and mild to moderate depression and anxiety symptoms. Objective test performance was largely uncorrelated with self-reports, mood, or illness severity, except for moderate correlations between complex attention and participants' subjective ratings of Everyday Task-Oriented Memory. CONCLUSIONS: These findings demonstrate specific long-term cognitive deficits associated with SARS and provide further evidence of the cognitive effects of hypoxic illnesses.

Facilitating change in health-related behaviors and intentions: a randomized controlled trial of a multidimensional memory program for older adults.

OBJECTIVES: Many older adults are concerned about memory changes with age and consequently seek ways to optimize their memory function. Memory programs are known to be variably effective in improving memory knowledge, other aspects of metamemory, and/or objective memory, but little is known about their impact on implementing and sustaining lifestyle and healthcare-seeking intentions and behaviors. METHODS: We evaluated a multidimensional, evidence-based intervention, the Memory and Aging Program, that provides education about memory and memory change, training in the use of practical memory strategies, and support for implementation of healthy lifestyle behavior changes. In a randomized controlled trial, 42 healthy older adults participated in a program (n = 21) or a waitlist control (n = 21) group. RESULTS: Relative to the control group, participants in the program implemented more healthy lifestyle behaviors by the end of the program and maintained these changes 1 month later. Similarly, program participants reported a decreased intention to seek unnecessary medical attention for their memory immediately after the program and 1 month later. CONCLUSIONS: Findings support the use of multidimensional memory programs to promote healthy lifestyles and influence healthcare-seeking behaviors. Discussion focuses on implications of these changes for maximizing cognitive health and minimizing impact on healthcare resources.

Are the memories of older adults positively biased?

There is disagreement in the literature about whether a "positivity effect" in memory performance exists in older adults. To assess the generalizability of the effect, the authors examined memory for autobiographical, picture, and word information in a group of younger (17-29 years old) and older (60-84 years old) adults. For the autobiographical memory task, the authors asked participants to produce 4 positive, 4 negative, and 4 neutral recent autobiographical memories and to recall these a week later. For the picture and word tasks, participants studied photos or words of different valences (positive, negative, neutral) and later remembered them on a free-recall test. The authors found significant correlations in memory performance, across task material, for recall of both positive and neutral valence autobiographical events, pictures, and words. When the authors examined accurate memories, they failed to find consistent evidence, across the different types of material, of a positivity effect in either age group. However, the false memory findings offer more consistent support for a positivity effect in older adults. During recall of all 3 types of material, older participants recalled more false positive than false negative memories.