Does memory reactivation during sleep support generalization at the cost of memory specifics?

Sleep is important for memory, but does it favor consolidation of specific details or extraction of generalized information? Both may occur together when memories are reactivated during sleep, or a loss of certain memory details may facilitate generalization. To examine these issues, we tested memory in participants who viewed landscape paintings by six artists. Paintings were cropped to show only a section of the scene. During a learning phase, each painting section was presented with the artist's name and with a nonverbal sound that had been uniquely associated with that artist. In a test of memory for specifics, participants were shown arrays of six painting sections, all by the same artist. Participants attempted to select the one that was seen in the learning phase. Generalization was tested by asking participants to view new paintings and, for each one, decide which of the six artists created it. After this testing, participants had a 90-minute sleep opportunity with polysomnographic monitoring. When slow-wave sleep was detected, three of the sound cues associated with the artists were repeatedly presented without waking the participants. After sleep, participants were again tested for memory specifics and generalization. Memory reactivation during sleep due to the sound cues led to a relative decline in accuracy on the specifics test, which could indicate the transition to a loss of detail that facilitates generalization, particularly details such as the borders. Generalization performance showed very little change after sleep and was unaffected by the sound cues. Although results tentatively implicate sleep in memory transformation, further research is needed to examine memory change across longer time periods.

Type 2 diabetes impairs the ability of skeletal muscle pericytes to augment postischemic neovascularization in db/db mice.

Peripheral artery disease is an atherosclerotic occlusive disease that causes limb ischemia and has few effective noninterventional treatments. Stem cell therapy is promising, but concomitant diabetes may limit its effectiveness. We evaluated the therapeutic potential of skeletal muscle pericytes to augment postischemic neovascularization in wild-type and type 2 diabetic (T2DM) mice. Wild-type C57BL/6J and leptin receptor spontaneous mutation db/db T2DM mice underwent unilateral femoral artery excision to induce limb ischemia. Twenty-four hours after ischemia induction, CD45-CD34-CD146+ skeletal muscle pericytes or vehicle controls were transplanted into ischemic hindlimb muscles. At postoperative day 28, pericyte transplantation augmented blood flow recovery in wild-type mice (79.3 ± 5% vs. 61.9 ± 5%; P = 0.04), but not in T2DM mice (48.6% vs. 46.3 ± 5%; P = 0.51). Pericyte transplantation augmented collateral artery enlargement in wild-type (26.7 ± 2 µm vs. 22.3 ± 1 µm, P = 0.03), but not T2DM mice (20.4 ± 1.4 µm vs. 18.5 ± 1.2 µm, P = 0.14). Pericyte incorporation into collateral arteries was higher in wild-type than in T2DM mice ( P = 0.002). Unexpectedly, pericytes differentiated into Schwann cells in vivo. In vitro, Insulin increased Nox2 expression and decreased tubular formation capacity in human pericytes. These insulin-induced effects were reversed by N-acetylcysteine antioxidant treatment. In conclusion, T2DM impairs the ability of pericytes to augment neovascularization via decreased collateral artery enlargement and impaired engraftment into collateral arteries, potentially via hyperinsulinemia-induced oxidant stress. While pericytes show promise as a unique form of stem cell therapy to increase postischemic neovascularization, characterizing the molecular mechanisms by which T2DM impairs their function is essential to achieve their therapeutic potential.

Distinguishing Neural Adaptation and Predictive Coding Hypotheses in Auditory Change Detection.

The auditory mismatch negativity (MMN) component of event-related potentials (ERPs) has served as a neural index of auditory change detection. MMN is elicited by presentation of infrequent (deviant) sounds randomly interspersed among frequent (standard) sounds. Deviants elicit a larger negative deflection in the ERP waveform compared to the standard. There is considerable debate as to whether the neural mechanism of this change detection response is due to release from neural adaptation (neural adaptation hypothesis) or from a prediction error signal (predictive coding hypothesis). Previous studies have not been able to distinguish between these explanations because paradigms typically confound the two. The current study disambiguated effects of stimulus-specific adaptation from expectation violation using a unique stimulus design that compared expectation violation responses that did and did not involve stimulus change. The expectation violation response without the stimulus change differed in timing, scalp distribution, and attentional modulation from the more typical MMN response. There is insufficient evidence from the current study to suggest that the negative deflection elicited by the expectation violation alone includes the MMN. Thus, we offer a novel hypothesis that the expectation violation response reflects a fundamentally different neural substrate than that attributed to the canonical MMN.

Endothelial and inflammatory responses to acute exercise in perimenopausal and late postmenopausal women.

Endothelial dysfunction and inflammation are characteristics of subclinical atherosclerosis and may increase through progressive menopausal stages. Evaluating endothelial responses to acute exercise can reveal underlying dysfunction not apparent in resting conditions. The purpose of this study was to investigate markers of endothelial function and inflammation before and after acute exercise in healthy low-active perimenopausal (PERI) and late postmenopausal (POST) women. Flow-mediated dilation (FMD), CD31+/CD42b- and CD62E+ endothelial microparticles (EMPs), and the circulating inflammatory factors monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8), and tumor necrosis factor-α (TNF-α) were measured before and 30 min after acute exercise. Before exercise, FMD was not different between groups (PERI: 6.4 ± 0.9% vs. POST: 6.5 ± 0.8%, P = 0.97); however, after acute exercise PERI tended to improve FMD (8.5 ± 0.9%, P = 0.09), whereas POST did not (6.2 ± 0.8%, P = 0.77). Independent of exercise, we observed transient endothelial dysfunction in POST with repeated FMD measures. There was a group × exercise interaction for CD31+/CD42b- EMPs (P = 0.04), where CD31+/CD42b- EMPs were similar before exercise (PERI: 57.0 ± 6.7 EMPs/µl vs. POST: 58.5 ± 5.3 EMPs/µl, P = 0.86) but were higher in POST following exercise (PERI: 48.2 ± 6.7 EMPs/µl vs. POST: 69.4 ± 5.3 EMPs/µl, P = 0.023). CD62E+ EMPs were lower in PERI compared with POST before exercise (P < 0.001) and increased in PERI (P = 0.04) but did not change in POST (P = 0.68) in response to acute exercise. After acute exercise, MCP-1 (P = 0.055), TNF-α (P = 0.02), and IL-8 (P < 0.001) were lower in PERI but only IL-8 decreased in POST (P < 0.001). Overall, these data suggest that perimenopausal and late postmenopausal women display different endothelial and inflammatory responses to acute exercise.

The influence of habitual physical activity and sedentary behavior on objective and subjective hot flashes at midlife.

OBJECTIVE: The purpose of this study was to evaluate relationships between physical activity, sedentary time, and hot flashes during both waking and sleeping periods using concurrent objective and subjective measures of hot flashes in midlife women. METHODS: Women aged 45 to 55 years (n = 196) provided self-reported data on physical activity and underwent 24 hours of hot flash monitoring using sternal skin conductance. Participants used event marking and logs to indicate when hot flashes were perceived. Wake and sleep periods were defined by actigraphy. Mean ambient temperature and humidity were recorded during the study period. Generalized linear regression modeling was used to evaluate the effect of physical activity types and sedentary time on hot flash outcomes. Isotemporal substitution modeling was used to study the effect of replacing sedentary time with activity variables on hot flash frequency. RESULTS: Modeled results indicated that increasing sitting by 1 hour was associated with a 7% increase in the rate of objectively measured but not subjectively reported hot flashes during sleep. Replacing 1 hour of sitting with 1 hour of vigorous activity was associated with a 100% increase in subjectively reported but not objectively measured waking hot flashes. There was little evidence for an effect of temperature or humidity on any hot flash outcome. CONCLUSIONS: These data provide support for relations between sedentary time, physical activity, and hot flashes and highlight the importance of using objective and subjective assessments to better understand the 24-hour hot flash experience.

Acute increases in physical activity and temperature are associated with hot flash experience in midlife women.

OBJECTIVE: This study determined the association between acute changes in physical activity, temperature, and humidity and 24-hour subjective and objective hot flash experience. METHODS: Data collection occurred during the cooler months of the year in Western Massachusetts (October-April). Women aged 45-55 across three menopause stages (n = 270) were instrumented with ambulatory monitors to continuously measure hot flashes, physical activity, temperature, and humidity for 24 hours. Objective hot flashes were assessed via sternal skin conductance, and subjective hot flashes were recorded by pressing an event marker and data logging. Physical activity was measured with wrist-worn accelerometers and used to define sleep and wake periods. Logistic multilevel modeling was used to examine the differences in physical activity, humidity, and temperature in the 10 minutes preceding a hot flash versus control windows when no hot flashes occurred. The odds of hot flashes were considered separately for objective and subjective hot flashes as well as for wake and sleep periods. RESULTS: Data from 188 participants were included in the analyses. There was a significantly greater odds of a hot flash following acute increases in physical activity for objective waking hot flashes (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.17-1.47; P < 0.001) and subjective waking hot flashes (OR, 1.16; 95% CI, 1.0-1.33; P = 0.03). Acute increases in the actigraphy signal were associated with significantly higher odds of having an objective (OR, 1.17; 95% CI, 1.03-1.35; P < 0.01) or subjective (OR, 1.72; 95% CI, 1.52-2.01; P < 0.001) sleeping hot flash. Increases in temperature were significantly related to the odds of subjective sleeping hot flashes only (OR, 1.38; 95% CI, 1.15-1.62; P < 0.001). There was no evidence for a relationship between humidity and odds of experiencing any hot flashes. CONCLUSION: These results indicate that acute increases in physical activity increase the odds of hot flashes that are objectively measured and subjectively reported during waking and sleeping periods. Temperature increases were only related to subjectively reported nighttime hot flashes.

Organic anion transporter 3 interacts selectively with lipophilic ß-lactam antibiotics.

Transporters are major determinants of the disposition of xenobiotics and endogenous chemicals in the body. Organic anion transporter 3 (Oat3) functions in the kidney and brain to remove metabolic waste, toxins, and drugs, and thus transports diverse chemicals. Some ß-lactam antibiotics interact with Oat3, and penicillin G exhibits a strong dependence on Oat3 for renal elimination. However, over 80 ß-lactams exist, and many have not been assessed for an interaction with Oat3. Moreover, ß-lactams continue to receive U.S. Food and Drug Administration approval. This study identified new ß-lactam-Oat3 interactions, provided a head-to-head comparison with Oat1, and characterized the physicochemical determinants of affinity for Oat3. Cells expressing mouse Oat3 (mOat3) and Oat1 (mOat1), and human OAT3 (hOAT3) were used to test inhibitors, and high-performance liquid chromatography (HPLC) was used to measure transport. Of 26 ß-lactams tested, 12 were clear inhibitors of Oat3, and 14 exhibited poor interactions. Inhibitors exhibited a nearly identical rank-order of potency against mOat3 and hOAT3. Oat1 demonstrated a poor interaction with most ß-lactams. The majority of Oat3 inhibitors were substrates, and there were clear physicochemical differences between inhibitors and noninhibitors. That is, inhibitors had nearly 40% fewer hydrogen bond donors (P < 0.001), a lower total polar surface area (P < 0.05), and greater lipophilicity (LogP of inhibitors, +1.41; noninhibitors, -1.54; P < 0.001). Pharmacophore mapping revealed a prohibitive hydrogen bond donor group in noninhibitors adjacent to a hydrophobic moiety that was important for binding to Oat3. These findings indicate that Oat3 recognizes lipophilic ß-lactams more readily. Moreover, this study has potential implications for designing ß-lactams to avoid renal accumulation or brain efflux via Oat3.

Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.

Early life and preconception environmental stimuli can affect adult health-related phenotypes. Exercise training is an environmental stimulus affecting many systems throughout the body and appears to alter offspring phenotypes. The aim of this study was to examine the influence of parental exercise training, or 'exercise ancestry', on morphological and metabolic phenotypes in two generations of mouse offspring. The F0 C57BL/6 mice were exposed to voluntary exercise (EX) or sedentary lifestyle (SED) and bred with like-exposed mates to produce an F1 generation. The F1 mice of both ancestries were sedentary and killed at 8 weeks or bred with littermates to produce an F2 generation, which was also sedentary and killed at 8 weeks. Small but broad generation- and sex-specific effects of exercise ancestry were observed for body mass, fat and muscle mass, serum insulin, glucose tolerance and muscle gene expression. The F1 EX females were lighter than F1 SED females and had lower absolute tibialis anterior and omental fat masses. Serum insulin was higher in F1 EX females compared with F1 SED females. The F2 EX females had impaired glucose tolerance compared with F2 SED females. Analysis of skeletal muscle mRNA levels revealed several generation- and sex-specific differences in mRNA levels for multiple genes, especially those related to metabolic genes (e.g. F1 EX males had lower mRNA levels of Hk2, Ppard, Ppargc1a, Adipoq and Scd1 than F1 SED males). These results provide preliminary evidence that parental exercise training can influence health-related phenotypes in mouse offspring.

Physical activity and exercise for hot flashes: trigger or treatment?

IMPORTANCE AND OBJECTIVE: Hot flashes (HFs) are a prevalent feature of menopause. Hot flashes can be bothersome and affect quality of life. However, HFs have also been associated with the risk for cardiovascular disease. Therefore, providing current evidence on the effect of therapies to reduce HFs can help patients and providers with decision making. This review provides details on the scientific evidence to date related to the effect of physical activity (PA) and exercise to alter the HF experience in women. METHODS: The PubMed database was searched between June 2020 and June 2022 for currently available evidence regarding the relation between PA and exercise and HFs. Our analysis included randomized control trials on exercise training, epidemiological studies, and studies evaluating acute exercise on the self-reported and objectively measured HF experience in addition to systematic reviews on the topic published as of June 2022. DISCUSSION AND CONCLUSIONS: The majority of evidence from randomized control trials indicates that aerobic and resistance exercise training lead to a decrease in subjectively experienced HFs. The limited available studies on acute exercise indicate that a bout of moderate-intensity exercise may decrease objectively measured and self-reported HFs but acute increases in PA intensity above accustomed levels may influence subjective HF experience. Some evidence suggests that for those with depression, habitual PA may be an effective way to reduce HF symptoms. Weighing the available evidence, for people who experience HFs, engaging in regular moderate-intensity PA, including aerobic and resistance exercise, may be an effective therapy to reduce HFs and women should be counseled on the benefits of regular, moderate exercise. However, significant gaps in knowledge remain about the optimal exercise prescription, effectiveness for a diverse population, meaning of differences between objective and subjective experience, and mechanisms that lead to changes in HFs.

The influence of menopause and cardiorespiratory fitness on lipoprotein particles in midlife women.

Lipoprotein particles may provide better information about cardiovascular risk than standard cholesterol measures for women. Whether lipoprotein subclasses change with menopausal stage is unclear. Given the high prevalence of low cardiorespiratory fitness in midlife women and benefit of cardiovascular disease risk, it is also important to understand the effect of fitness on lipoprotein profiles. This study evaluated the influence of menopausal status and fitness on lipoprotein particles in healthy midlife women. Lipoprotein particles were measured in high- (n = 25) and low- (n = 13) fit perimenopausal and late postmenopausal women, and in high-fit premenopausal (n = 10), perimenopausal (n = 12), and late postmenopausal women (n = 13). There were larger low-density lipoprotein particles (LDL-P; 21.7 ± 0.06 vs. 21.3 ± 0.1 nm, p = 0.002), more large LDL-P (623.1 ± 32.8 vs. 500.2 ± 52.6 nmol/L, p = 0.045), and fewer small LDL-P (145.5 ± 31.4 vs. 311.5 ± 44.7 nmol/L, p = 0.001) in the high-fit group vs. the low-fit group. High-density lipoprotein particles (HDL-P) were larger (10.1 ± 0.1 vs. 9.7 ± 0.1 nm, p = 0.002) in the high-fit group, with more large (14.8 ± 0.7 vs. 11.0 ± 0.9 µmol/L, p = 0.002), medium (12.9 ± 0.8 vs. 8.4 ± 0.9 µmol/L, p = 0.002) HDL-P, and fewer small HDL-P (10.2 ± 1.1 vs. 15.4 ± 1.6 µmol/L, p = 0.009) compared with the low-fit group. High-fit postmenopausal women had more large LDL-P (662.9 ± 47.5 nmol/L) compared with premenopausal women (479.1 ± 52.6 nmol/L, p = 0.035), and more HDL-P (40.2 ± 1.1 µmol/L) compared with premenopausal (34.9 ± 1.5 µmol/L, p = 0.023) and perimenopausal women (35.4 ± 1.3 µmol/L, p = 0.033). High fitness positively influences lipoprotein particles in healthy perimenopausal and late postmenopausal women. In healthy fit women, menopause may not have a large influence on lipoprotein particles. Novelty: In highly fit women, menopause may not have a negative influence on lipoprotein particle subclasses. High fitness is associated with a less atherogenic lipoprotein profile in perimenopausal and late postmenopausal women.

A comparison of stress, symptoms, physical activity, and adiposity among women at midlife before and during the pandemic.

BACKGROUND: The COVID-19 pandemic presented challenges that disproportionately impacted women. Household roles typically performed by women (such as resource acquisition and caretaking) became more difficult due to financial strain, fear of infection, and limited childcare options among other concerns. This research draws from an on-going study of hot flashes and brown adipose tissue to examine the health-related effects of the COVID-19 pandemic among 162 women aged 45-55 living in western Massachusetts. METHODS: We compared women who participated in the study pre- and early pandemic with women who participated mid-pandemic and later-pandemic (when vaccines became widely available). We collected self-reported symptom frequencies (e.g., aches/stiffness in joints, irritability), and assessments of stress, depression, and physical activity through questionnaires as well as measures of adiposity (BMI and percent body fat). Additionally, we asked open-ended questions about how the pandemic influenced women's health and experience of menopause. Comparisons across pre-/early, mid-, and later pandemic categories were carried out using ANOVA and Chi-square analyses as appropriate. The Levene test for homogeneity of variances was examined prior to each ANOVA. Open-ended questions were analyzed for yes/no responses and general themes. RESULTS: Contrary to our hypothesis that women would suffer negative health-related consequences during the COVID-19 pandemic, we found no significant differences in women's health-related measures or physical activity across the pandemic. However, our analysis of open-ended responses revealed a bi-modal distribution of answers that sheds light on our unexpected findings. While some women reported higher levels of stress and anxiety and lower levels of physical activity, other women reported benefitting from the remote life that the pandemic imposed and described having more time to spend on physical activity or in quality time with their families. CONCLUSIONS: In this cross-sectional comparison of women during the pre-/early, mid-, and later-pandemic, we found no significant differences across means in multiple health-related variables. However, open-ended questions revealed that while some women suffered health-related effects during the pandemic, others experienced conditions that improved their health and well-being. The differential results of this study highlight a need for more nuanced and intersectional research on risk, vulnerabilities, and coping among mid-life women.

AKT1 G205T genotype influences obesity-related metabolic phenotypes and their responses to aerobic exercise training in older Caucasians.

As part of the insulin signalling pathway, Akt influences growth and metabolism. The AKT1 gene G205T (rs1130214) polymorphism has potential functional effects. Thus, we determined whether the G205T polymorphism influences metabolic variables and their responses to aerobic exercise training. Following dietary stabilization, healthy, sedentary, 50- to 75-year-old Caucasian men (n = 51) and women (n = 58) underwent 6 months of aerobic exercise training. Before and after completing the intervention, dual-energy X-ray absorptiometry was used to measure percentage body fat, computed tomography to measure visceral and subcutaneous fat, and oral glucose tolerance testing to measure glucose total area under the curve (AUC), insulin AUC and insulin sensitivity. Taqman assay was used to determine AKT1 G205T genotypes. At baseline, men with the GG genotype (n = 29) had lower maximal oxygen consumption (VO2 max) values (P = 0.026) and higher percentage body fat (P = 0.046), subcutaneous fat (P = 0.021) and insulin AUC (P = 0.003) values than T allele carriers (n = 22). Despite their rather disadvantageous starting values, men with the GG genotype seemed to respond to exercise training more robustly than men with the T allele, highlighted by significantly greater fold change improvements in insulin AUC (P = 0.012) and glucose AUC (P = 0.035). Although the GG group also significantly improved VO2 max with training, the change in VO2 max was not as great as that of the T allele carriers (P = 0.037). In contrast, after accounting for hormone replacement therapy use, none of the variables differed in the women at baseline. As a result of exercise training, women with the T allele (n = 20) had greater fold change improvements in fasting glucose (P = 0.011), glucose AUC (P = 0.017) and insulin sensitivity (P = 0.044) than GG genotype women (n = 38). Our results suggest that the AKT1 G205T polymorphism influences metabolic variables and their responses to aerobic exercise training in older, previously sedentary individuals.

Enhancing treatment for cardiovascular disease: exercise and circulating angiogenic cells.

The discovery of circulating angiogenic cells (CAC) with cardiovascular regenerative potential has transformed our understanding of the health and maintenance of cardiovascular tissues. We will describe the influence of acute exercise and exercise training on CAC characteristics and evidence for mechanisms that may be important in the optimization of CAC potential.

The role of cardiorespiratory fitness on quality of life in midlife women.

OBJECTIVE: We aimed to characterize the relationship between cardiorespiratory fitness and quality of life in a sample of healthy midlife women aged 40 to 65 years. METHODS: Cardiorespiratory fitness was measured with a VO2max test. Quality of life was assessed with the menopause-specific Utian Quality of Life scale (UQOL). The UQOL measures overall quality of life, which comprises health, emotional, occupational, and sexual domains. Simple and multiple linear regression models were built to analyze relationships between cardiorespiratory fitness and overall quality of life as well as the separate UQOL domains. RESULTS: Forty-nine women with an average age of 52.5 years were included in the analysis. In simple linear models, cardiorespiratory fitness was related to overall (R2 = 0.34, P < 0.001), health (R2 = 0.55, P < 0.001), emotional (R2 = 0.08, P = 0.05), and occupational (R2 = 0.09, P = 0.03) quality of life. In multiple regression models, cardiorespiratory fitness was associated with overall (P < 0.01) and health (P < 0.001) quality of life, after controlling for physical activity, age, body mass index, and time sedentary. CONCLUSIONS: Higher cardiorespiratory fitness is associated with better quality of life during midlife, particularly in the health domain. Increasing cardiorespiratory fitness may be a useful means to promote quality of life in this population.

Real-time dialogue between experimenters and dreamers during REM sleep.

Dreams take us to a different reality, a hallucinatory world that feels as real as any waking experience. These often-bizarre episodes are emblematic of human sleep but have yet to be adequately explained. Retrospective dream reports are subject to distortion and forgetting, presenting a fundamental challenge for neuroscientific studies of dreaming. Here we show that individuals who are asleep and in the midst of a lucid dream (aware of the fact that they are currently dreaming) can perceive questions from an experimenter and provide answers using electrophysiological signals. We implemented our procedures for two-way communication during polysomnographically verified rapid-eye-movement (REM) sleep in 36 individuals. Some had minimal prior experience with lucid dreaming, others were frequent lucid dreamers, and one was a patient with narcolepsy who had frequent lucid dreams. During REM sleep, these individuals exhibited various capabilities, including performing veridical perceptual analysis of novel information, maintaining information in working memory, computing simple answers, and expressing volitional replies. Their responses included distinctive eye movements and selective facial muscle contractions, constituting correctly answered questions on 29 occasions across 6 of the individuals tested. These repeated observations of interactive dreaming, documented by four independent laboratory groups, demonstrate that phenomenological and cognitive characteristics of dreaming can be interrogated in real time. This relatively unexplored communication channel can enable a variety of practical applications and a new strategy for the empirical exploration of dreams.

Relationship between circulating progenitor cells, vascular function and oxidative stress with long-term training and short-term detraining in older men.

Exercise may contribute to the maintenance of vascular function via enhanced liberation and action of bone-marrow-derived progenitor cells. Activity related changes in oxidative stress may also influence the number and function of these cells. In the present study, we sought to determine (i) whether adaptations in reactive hyperaemic FBF (forearm blood flow) response associated with long-term endurance exercise and short-term detraining were related to resting putative progenitor cell number and function, and (ii) whether oxidative stress affected these factors. Participants included men with a history of more than 30 years of moderate-to-high intensity exercise (HI group) and healthy low-active age- and BMI (body mass index)-matched control subjects (LO group). Vascular reactive hyperaemic FBF response, resting CD34+ and CD34+/VEGFR2+ (vascular endothelial growth factor receptor 2+] cell number, CFU-EC (colony forming unit-endothelial cell) count and CFU-EC senescence were evaluated. Oxidative stress measures included OxLDL (oxidized low-density lipoprotein) and TAC (total antioxidant capacity).These measures were assessed following 10 days of detraining in the HI group. The HI group had greater peak reactive hyperaemic FBF responses compared with the LO group, despite no difference in resting CD34+ cell number, CD34+/VEGFR2+ cell number, CFU-EC colonies or CFU-EC senescence. With detraining in the HI group, CD34+ cells declined 44 %, and the percentage change in CD34+/VEGFR2+ cells was positively correlated with the change in FBF response to reactive hyperaemia. The percentage change in CD34+/VEGFR2+ cells and the percentage change in EPC (endothelial progenitor cell) senescence with detraining were related to the percentage change in TAC. These results reveal that changes in reactive hyperaemic FBF are closely related to activity dependent dynamic changes in CD34+/VEGFR2+ cell number, which may be influenced by alterations in oxidative stress.

Author Correction: Targeted memory reactivation during sleep boosts intentional forgetting of spatial locations.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Targeted memory reactivation during sleep boosts intentional forgetting of spatial locations.

Although we experience thousands of distinct events on a daily basis, relatively few are committed to memory. The human capacity to intentionally control which events will be remembered has been demonstrated using learning procedures with instructions to purposely avoid committing specific items to memory. In this study, we used a variant of the item-based directed-forgetting procedure and instructed participants to memorize the location of some images but not others on a grid. These instructions were conveyed using a set of auditory cues. Then, during an afternoon nap, we unobtrusively presented a cue that was used to instruct participant to avoid committing the locations of some images to memory. After sleep, memory was worse for to-be-forgotten image locations associated with the presented sound relative to those associated with a sound that was not presented during sleep. We conclude that memory processing during sleep can serve not only to secure memory storage but also to weaken it. Given that intentional suppression may be used to weaken unpleasant memories, such sleep-based strategies may help accelerate treatments for memory-related disorders such as post-traumatic stress disorder.

Effects of acute and chronic endurance exercise on intracellular nitric oxide in putative endothelial progenitor cells: role of NAPDH oxidase.

We sought to delineate the effects of acute and chronic exercise on the regulation of intracellular nitric oxide (NO(i)) production in putative endothelial progenitor cells (EPCs). Putative EPC colony-forming units (CFU-EC) were cultured from blood drawn before and after 30 min of treadmill exercise at 75% of maximal oxygen uptake in active (n = 8) and inactive (n = 8) men. CFU-EC were similar between groups at baseline, but increased after exercise in active men only (P = 0.04). CFU-EC expressed lower NADPH oxidase subunit gp91(phox) mRNA and elevated endothelial nitric oxide synthase mRNA in active relative to inactive men at baseline (P < 0.05). Acute exercise reduced gp91(phox) mRNA in CFU-EC of both groups (P < 0.05), whereas p47(phox) mRNA levels were reduced in the inactive group only (P = 0.02). There were no differences between groups or with acute exercise in xanthine oxidase, superoxide dismutase isoforms, or gluthathione peroxidase-1 mRNA levels. NO(i) was significantly greater in CFU-EC of active men at baseline (P = 0.004). NO(i) increased in CFU-EC of inactive men with acute exercise, and in vitro experiments with apocynin indicated the increased NO(i) production was caused by suppression of NADPH oxidase. However, the increases in NO(i) with the different treatments in the inactive group did not reach the baseline levels in the active group (P < 0.05). We conclude that acute exercise increases NO(i) in cells generated by the CFU-EC assay through an NADPH oxidase-inhibition mechanism in sedentary men. However, differences due to chronic exercise must involve additional factors. Our findings support exercise as a means to improve putative EPC function and suggest a novel mechanism that may explain this effect.