Concurrent invasions of European starlings in Australia and North America reveal population-specific differentiation in shared genomic regions.

A species' success during the invasion of new areas hinges on an interplay between the demographic processes common to invasions and the specific ecological context of the novel environment. Evolutionary genetic studies of invasive species can investigate how genetic bottlenecks and ecological conditions shape genetic variation in invasions, and our study pairs two invasive populations that are hypothesized to be from the same source population to compare how each population evolved during and after introduction. Invasive European starlings (Sturnus vulgaris) established populations in both Australia and North America in the 19th century. Here, we compare whole-genome sequences among native and independently introduced European starling populations to determine how demographic processes interact with rapid evolution to generate similar genetic patterns in these recent and replicated invasions. Demographic models indicate that both invasive populations experienced genetic bottlenecks as expected based on invasion history, and we find that specific genomic regions have differentiated even on this short evolutionary timescale. Despite genetic bottlenecks, we suggest that genetic drift alone cannot explain differentiation in at least two of these regions. The demographic boom intrinsic to many invasions as well as potential inversions may have led to high population-specific differentiation, although the patterns of genetic variation are also consistent with the hypothesis that this infamous and highly mobile invader adapted to novel selection (e.g., extrinsic factors). We use targeted sampling of replicated invasions to identify and evaluate support for multiple, interacting evolutionary mechanisms that lead to differentiation during the invasion process.

Evolution of atrophied T2 lesion volume in primary-progressive multiple sclerosis: results from the phase 3 ORATORIO study.

BACKGROUND: Atrophied T2-lesion volume (aT2-LV) is an exploratory imaging marker in multiple sclerosis (MS) reflecting the volume of lesions subsumed into cerebrospinal fluid (CSF). OBJECTIVE: To investigate the effect of ocrelizumab (OCR) versus placebo (PBO) over 120 weeks on the accumulation of aT2-LV in a double-blind placebo-controlled (DBP) phase 3, primary-progressive (PP) MS study (ORATORIO; NCT01194570). METHODS: This post-hoc, MRI-blinded analysis evaluated 732 PPMS randomised to OCR (488) or PBO (244). Atrophied T2-LV was calculated by overlaying baseline T2-lesion masks on follow-up CSF maps. Clinical data from DBP and open-label extension (OLE) periods were available. Treatment effect was evaluated by a mixed-effect model with repeated measures, while logistic regression explored the association of aT2-LV at week 120 and clinical outcomes in the OLE period. RESULTS: OCR treatment significantly reduced accumulation of aT2-LV compared with PBO (319.4 mm3 vs 366.1 mm3, p=0.015) at 120 weeks. OCR showed superiority over PBO in reducing aT2-LV in patients who developed confirmed disability progression (CDP) during the DBP period at 12 (CDP12) and 24 (CDP24) weeks for the composite of Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test and Timed 25-Foot Walk test. Accumulation of aT2-LV at week 120 was related to CDP12-EDSS (p=0.018) and CDP24-EDSS (p=0.022) in the OLE for the patients who were treated by PBO in the DBP only. CONCLUSIONS: OCR showed a significant effect of reducing the accumulation of aT2-LV in PPMS in the DBP period and was related to CDP-EDSS in OLE only in the PBO arm.

Intermittent fasting and bone health: a bone of contention?

Intermittent fasting (IF) is a promising strategy for weight loss and improving metabolic health, but its effects on bone health are less clear. This review aims to summarise and critically evaluate the preclinical and clinical evidence on IF regimens (the 5:2 diet, alternate-day fasting (ADF) and time-restricted eating (TRE)/time-restricted feeding and bone health outcomes. Animal studies have utilised IF alongside other dietary practices known to elicit detrimental effects on bone health and/or in models mimicking specific conditions; thus, findings from these studies are difficult to apply to humans. While limited in scope, observational studies suggest a link between some IF practices (e.g. breakfast omission) and compromised bone health, although lack of control for confounding factors makes these data difficult to interpret. Interventional studies suggest that TRE regimens practised up to 6 months do not adversely affect bone outcomes and may even slightly protect against bone loss during modest weight loss (< 5 % of baseline body weight). Most studies on ADF have shown no adverse effects on bone outcomes, while no studies on the '5­2' diet have reported bone outcomes. Available interventional studies are limited by their short duration, small and diverse population samples, assessment of total body bone mass exclusively (by dual-energy X-ray absorptiometry) and inadequate control of factors that may affect bone outcomes, making the interpretation of existing data challenging. Further research is required to better characterise bone responses to various IF approaches using well-controlled protocols of sufficient duration, adequately powered to assess changes in bone outcomes and designed to include clinically relevant bone assessments.

Effects of Morning Vs. Evening exercise on appetite, energy intake, performance and metabolism, in lean males and females.

Exercise is an important component of a weight management strategy. However, little is known about whether circadian variations in physiological and behavioural processes can influence the appetite and energy balance responses to exercise performed at different times of the day. This study compared the effects of morning and evening exercise on appetite, post-exercise energy intake, and voluntary performance. In randomised, counterbalanced order, 16 healthy males and females (n = 8 each) completed two trials, performing morning exercise at 10:30 (AMEx) or evening exercise at 18:30 (PMEx). Exercise consisted of 30 min steady-state cycling (60% V˙ O2peak), and a 15-min performance test. A standardised meal (543 ± 86 kcal) was consumed 2-h before exercise and ad-libitum energy intake was assessed 15 min after exercise, with subjective appetite measured throughout. Absolute ad-libitum energy intake was 152 ± 126 kcal greater during PMEx (P < 0.001), but there was no differences in subjective appetite between trials immediately pre-exercise, or immediately before the post-exercise meal (P ≥ 0.060). Resting energy expenditure (P < 0.01) and carbohydrate oxidation (P < 0.05) were greater during AMEx, but there were no differences in substrate oxidation or energy expenditure during exercise (P ≥ 0.155). Exercise performance was not different between trials (P = 0.628). In conclusion, acute morning and evening exercise prompt similar appetite responses, but post-exercise ad-libitum energy intake is greater following evening exercise. These findings demonstrate discordant responses between subjective appetite and ad-libitum energy intake but suggest that exercise might offset circadian variations in appetite. Longer-term studies are required to determine how exercise timing affects adherence and weight management outcomes to exercise interventions. TRIAL REGISTRATION: NCT04742530, February 8, 2021.

The role of the genome in experience-dependent plasticity: Extending the analogy of the genomic action potential.

Our past experiences shape our current and future behavior. These experiences must leave some enduring imprint on our brains, altering neural circuits that mediate behavior and contributing to our individual differences. As a framework for understanding how experiences might produce lasting changes in neural circuits, Clayton [D. F. Clayton, Neurobiol. Learn. Mem. 74, 185-216 (2000)] introduced the concept of the genomic action potential (gAP)-a structured genomic response in the brain to acute experience. Similar to the familiar electrophysiological action potential (eAP), the gAP also provides a means for integrating afferent patterns of activity but on a slower timescale and with longer-lasting effects. We revisit this concept in light of contemporary work on experience-dependent modification of neural circuits. We review the "Immediate Early Gene" (IEG) response, the starting point for understanding the gAP. We discuss evidence for its involvement in the encoding of experience to long-term memory across time and biological levels of organization ranging from individual cells to cell ensembles and whole organisms. We explore distinctions between memory encoding and homeostatic functions and consider the potential for perpetuation of the imprint of experience through epigenetic mechanisms. We describe a specific example of a gAP in humans linked to individual differences in the response to stress. Finally, we identify key objectives and new tools for continuing research in this area.

Acute social isolation alters neurogenomic state in songbird forebrain.

Prolonged social isolation has negative effects on brain and behavior in humans and other social organisms, but neural mechanisms leading to these effects are not understood. Here we tested the hypothesis that even brief periods of social isolation can alter gene expression and DNA methylation in higher cognitive centers of the brain, focusing on the auditory/associative forebrain of the highly social zebra finch. Using RNA sequencing, we first identified genes that individually increase or decrease expression after isolation and observed general repression of gene sets annotated for neurotrophin pathways and axonal guidance functions. We then pursued 4 genes of large effect size: EGR1 and BDNF (decreased by isolation) and FKBP5 and UTS2B (increased). By in situ hybridization, each gene responded in different cell subsets, arguing against a single cellular mechanism. To test whether effects were specific to the social component of the isolation experience, we compared gene expression in birds isolated either alone or with a single familiar partner. Partner inclusion ameliorated the effect of solo isolation on EGR1 and BDNF, but not on FKBP5 and UTS2B nor on circulating corticosterone. By bisulfite sequencing analysis of auditory forebrain DNA, isolation caused changes in methylation of a subset of differentially expressed genes, including BDNF. Thus, social isolation has rapid consequences on gene activity in a higher integrative center of the brain, triggering epigenetic mechanisms that may influence processing of ongoing experience.

Fasting Before Evening Exercise Reduces Net Energy Intake and Increases Fat Oxidation, but Impairs Performance in Healthy Males and Females.

Acute morning fasted exercise may create a greater negative 24-hr energy balance than the same exercise performed after a meal, but research exploring fasted evening exercise is limited. This study assessed the effects of 7-hr fasting before evening exercise on energy intake, metabolism, and performance. Sixteen healthy males and females (n = 8 each) completed two randomized, counterbalanced trials. Participants consumed a standardized breakfast (08:30) and lunch (11:30). Two hours before exercise (16:30), participants consumed a meal (543 ± 86 kcal; FED) or remained fasted (FAST). Exercise involved 30-min cycling (∼60% VO2peak) and a 15-min performance test (∼85% VO2peak; 18:30). Ad libitum energy intake was assessed 15 min postexercise. Subjective appetite was measured throughout. Energy intake was 99 ± 162 kcal greater postexercise (p < .05), but 443 ± 128 kcal lower over the day (p < .001) in FAST. Appetite was elevated between the preexercise meal and ad libitum meal in FAST (p < .001), with no further differences (p ≥ .458). Fat oxidation was greater (+3.25 ± 1.99 g), and carbohydrate oxidation was lower (-9.16 ± 5.80 g) during exercise in FAST (p < .001). Exercise performance was 3.8% lower in FAST (153 ± 57 kJ vs. 159 ± 58 kJ, p < .05), with preexercise motivation, energy, readiness, and postexercise enjoyment also lower in FAST (p < .01). Fasted evening exercise reduced net energy intake and increased fat oxidation compared to exercise performed 2 hr after a meal. However, fasting also reduced voluntary performance, motivation, and exercise enjoyment. Future studies are needed to examine the long-term effects of this intervention as a weight management strategy.

Joint MRI T1 Unenhancing and Contrast-enhancing Multiple Sclerosis Lesion Segmentation with Deep Learning in OPERA Trials.

Background Deep learning-based segmentation could facilitate rapid and reproducible T1 lesion load assessments, which is crucial for disease management in multiple sclerosis (MS). T1 unenhancing and contrast-enhancing lesions in MS are those that enhance or do not enhance after administration of a gadolinium-based contrast agent at T1-weighted MRI. Purpose To develop deep learning models for automated assessment of T1 unenhancing and contrast-enhancing lesions; to investigate if joint training improved performance; to reproduce a known ocrelizumab treatment response; and to evaluate the association of baseline T1-weighted imaging metrics with clinical outcomes in relapsing MS clinical trials. Materials and Methods Joint and individual deep learning models (U-Nets) were developed retrospectively on multimodal MRI data sets from large multicenter OPERA trials of relapsing MS (August 2011 to May 2015). The joint model included cross-network connections and a combined loss function. Models were trained on OPERA I data sets with three-fold cross-validation. OPERA II data sets were the internal test set. Dice coefficients, lesion true-positive and false-positive rates, and areas under the receiver operating characteristic curve (AUCs) were used to evaluate model performance. Association of baseline imaging metrics with clinical outcomes was assessed with Cox proportional hazards models. Results A total of 796 patients (3030 visits; mean age, 37 years ± 9; 521 women) from the OPERA II trial were evaluated. The joint model achieved a mean Dice coefficient of 0.77 and 0.74, lesion true-positive rate of 0.88 and 0.86, and lesion false-positive rate of 0.04 and 0.19 for T1 contrast-enhancing and T1 unenhancing lesion segmentation, respectively. Joint training improved performance for smaller T1 contrast-enhancing lesions (≤0.06 mL; individual training AUC: 0.75; joint training AUC: 0.87; P < .001). A significant ocrelizumab treatment effect (P < .001) was seen in reducing the mean number of T1 contrast-enhancing lesions at 24, 48, and 96 weeks (manual assessment at 24 weeks: 10 lesions in 366 patients with ocrelizumab, 141 lesions in 355 patients with interferon, 93% reduction; manual assessment at 48 weeks: six lesions in 355 patients with ocrelizumab, 150 lesions in 317 patients with interferon, 96% reduction; manual assessment at 96 weeks: five lesions in 340 patients with ocrelizumab, 157 lesions in 294 patients with interferon, 97% reduction; joint model assessment at 24 weeks: 19 lesions in 365 patients with ocrelizumab, 128 lesions in 354 patients with interferon, 86% reduction; joint model assessment at 48 weeks: 14 lesions in 355 patients with ocrelizumab, 121 lesions in 317 patients with interferon, 90% reduction; joint model assessment at 96 weeks: 10 lesions in 340 patients with ocrelizumab, 144 lesions in 294 patients with interferon, 94% reduction) and the mean number of new T1 unenhancing lesions across all follow-up examinations (manual assessment: 504 lesions in 1060 visits for ocrelizumab-treated patients, 1438 lesions in 965 visits for interferon-treated patients, 68% reduction; joint model assessment: 205 lesions in 1053 visits for ocrelizumab-treated patients, 661 lesions in 957 visits for interferon-treated patients, 78% reduction). Baseline T1 unenhancing total lesion volume was associated with clinical outcomes (manual hazard ratio [HR]: 1.12, P = .02; joint model HR: 1.11, P = .03). Conclusion Joint architecture and training improved segmentation of MRI T1 contrast-enhancing multiple sclerosis lesions, and both deep learning models had sufficiently high performance to detect an ocrelizumab treatment response consistent with manual assessments. ClinicalTrials.gov: NCT01247324 and NCT01412333 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Talbott in this issue.

Effect of the perception of breakfast consumption on subsequent appetite and energy intake in healthy males.

PURPOSE: This study aimed to assess the effects of consuming a very-low-energy placebo breakfast on subsequent appetite and lunch energy intake. METHODS: Fourteen healthy males consumed water-only (WAT), very-low-energy, viscous placebo (containing water, low-calorie flavoured squash, and xanthan gum; ~ 16 kcal; PLA), and whole-food (~ 573 kcal; FOOD) breakfasts in a randomised order. Subjects were blinded to the energy content of PLA and specific study aims. Venous blood samples were collected pre-breakfast, 60- and 180-min post-breakfast to assess plasma acylated ghrelin and peptide tyrosine tyrosine concentrations. Subjective appetite was measured regularly, and energy intake was assessed at an ad libitum lunch meal 195-min post-breakfast. RESULTS: Lunch energy intake was lower during FOOD compared to WAT (P < 0.05), with no further differences between trials (P ≥ 0.132). Cumulative energy intake (breakfast plus lunch) was lower during PLA (1078 ± 274 kcal) and WAT (1093 ± 249 kcal), compared to FOOD (1554 ± 301 kcal; P < 0.001). Total area under the curve (AUC) for hunger, desire to eat and prospective food consumption were lower, and fullness was greater during PLA and FOOD compared to WAT (P < 0.05). AUC for hunger was lower during FOOD compared to PLA (P < 0.05). During FOOD, acylated ghrelin was suppressed compared to PLA and WAT at 60 min (P < 0.05), with no other hormonal differences between trials (P ≥ 0.071). CONCLUSION: Consuming a very-low-energy placebo breakfast does not alter energy intake at lunch but may reduce cumulative energy intake across breakfast and lunch and attenuate elevations in subjective appetite associated with breakfast omission. TRIAL REGISTRATION: NCT04735783, 2nd February 2021, retrospectively registered.

Sex differences in cognitive resilience in preclinical autosomal-dominant Alzheimer's disease carriers and non-carriers: Baseline findings from the API ADAD Colombia Trial.

INTRODUCTION: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers. METHODS: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing. RESULTS: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory. DISCUSSION: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience.

Social isolation and the role of AgeTech in a post-COVID world.

The COVID-19 pandemic particularly affected social connection through enforced social isolation and loss of regular activities. For healthcare systems, various initiatives have sprung up, leveraging existing technologies to connect people with services, activities, and loved ones. Here we review some AgeTech offerings to address social isolation for healthcare leadership and management to consider.

Severely restricting energy intake for 24 h does not affect markers of bone metabolism at rest or in response to re-feeding.

PURPOSE: Intermittent energy restriction commonly refers to ad libitum energy intake punctuated with 24 h periods of severe energy restriction. This can improve markers of metabolic health but the effects on bone metabolism are unknown. This study assessed how 24 h severe energy restriction and subsequent refeeding affected markers of bone turnover. METHODS: In a randomised order, 16 lean men and women completed 2, 48 h trials over 3 days. On day 1, participants consumed a 24 h diet providing 100% [EB: 9.27 (1.43) MJ] or 25% [ER: 2.33 (0.34) MJ] of estimated energy requirements. On day 2, participants consumed a standardised breakfast (08:00), followed by an ad libitum lunch (12:00) and dinner (19:30). Participants then fasted overnight, returning on day 3. Plasma concentrations of C-terminal telopeptide of type I collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and parathyroid hormone (PTH) were assessed as indices of bone metabolism after an overnight fast on days 1-3, and for 4 h after breakfast on day 2. RESULTS: There were no differences between trials in fasting concentrations of CTX, P1NP or PTH on days 1-3 (P > 0.512). During both trials, consuming breakfast reduced CTX between 1 and 4 h (P < 0.001) and PTH between 1 and 2 h (P < 0.05), but did not affect P1NP (P = 0.773) Postprandial responses for CTX (P = 0.157), P1NP (P = 0.148) and PTH (P = 0.575) were not different between trials. Ad libitum energy intake on day 2 was greater on ER [12.62 (2.46) MJ] than EB [11.91 (2.49) MJ]. CONCLUSIONS: Twenty-four hour severe energy restriction does not affect markers of bone metabolism.

Anticipation of 24 h severe energy restriction increases energy intake and reduces physical activity energy expenditure in the prior 24 h, in healthy males.

Intermittent fasting involves alternating between severely restricted and unrestricted energy intake. Physical activity energy expenditure (PAEE) is reduced during, and energy intake is elevated after, a period of energy restriction, but whether these are altered in anticipation of energy restriction is unknown. The aim of this study was to assess energy intake and PAEE in the 24 h before severe energy restriction. In randomised, counterbalanced order, 14 healthy males completed two 48 h trials over 3 days. On day 1, participants were informed which diet they would receive on day 2; either an energy balanced diet providing 100% (2755 (159) kcal; EB) or an energy restricted diet providing 25% (691 (42) kcal; ER), of their estimated energy requirements. Throughout day 1, ad-libitum energy intake was then determined from researcher-provided breakfast (08:30-09:00), lunch (12:30-13:00), afternoon snacks (14:00-18:00) and dinner (19:30-20:00). On day 2, participants consumed their allocated diet as instructed. On day 3, ad-libitum energy intake was assessed at breakfast (08:30-09:00). PAEE was measured throughout via integrated heart-rate and accelerometry monitors. Energy intake was 6% greater on day 1 (260 (344) kcal; P < 0.05) and 14% greater at breakfast on day 3 (223 (59) kcal; P < 0.05) during ER compared to EB. PAEE was 156 (252) kcal lower on day 1 (P < 0.05) and 239 (391) lower on day 2 (P < 0.05) during ER compared to EB. These behavioural compensations meant that the energy deficit produced by 24 h severe energy restriction was attenuated by 1108 (415) kcal (46%) over the study period (P < 0.0001). These results suggest that compensatory changes in energy intake and PAEE occur before, during and after an acute 24 h period of severe energy restriction, likely lessening the energy deficit created.

An acute bout of swimming increases post-exercise energy intake in young healthy men and women.

Single bouts of land-based exercise (for example, walking, running, cycling) do not typically alter post-exercise energy intake on the day of exercise. However, anecdotal and preliminary empirical evidence suggests that swimming may increase appetite and energy intake. This study compared the acute effects of swimming on appetite, energy intake, and food preference and reward, versus exertion-matched cycling and a resting control. Thirty-two men (n = 17; mean ± SD age 24 ± 2 years, body mass index [BMI] 25.0 ± 2.6 kg/m2) and women (n = 15; age 22 ± 3 years, BMI 22.8 ± 2.3 kg/m2) completed three experimental trials (swimming, cycling, control) in a randomised, crossover design. The exercise trials involved 60-min of 'hard' exercise (self-selected rating of perceived exertion: 15) performed 90-min after a standardised breakfast. Food preference and reward were assessed via the Leeds Food Preference Questionnaire 15-min after exercise, whilst ad libitum energy intake was determined 30-min after exercise. The control trial involved identical procedures except no exercise was performed. Compared with control (3259 ± 1265 kJ), swimming increased ad libitum energy intake (3857 ± 1611 kJ; ES = 0.47, 95% CI of the mean difference between trials 185, 1010 kJ, P = 0.005); the magnitude of increase was smaller after cycling (3652 ± 1619 kJ; ES = 0.31, 95% CI -21, 805 kJ, P = 0.062). Ad libitum energy intake was similar between swimming and cycling (ES = 0.16, 95% CI -207, 618 kJ, P = 0.324). This effect was consistent across sexes and unrelated to food preference and reward which were similar after swimming and cycling compared with control. This study has identified an orexigenic effect of swimming. Further research is needed to identify the responsible mechanism(s), including the relevance of water immersion and water temperature per se.

Quantitative neuroimaging measures of myelin in the healthy brain and in multiple sclerosis.

Quantitative magnetic resonance imaging (MRI) techniques have been developed as imaging biomarkers, aiming to improve the specificity of MRI to underlying pathology compared to conventional weighted MRI. For assessing the integrity of white matter (WM), myelin, in particular, several techniques have been proposed and investigated individually. However, comparisons between these methods are lacking. In this study, we compared four established myelin-sensitive MRI techniques in 56 patients with relapsing-remitting multiple sclerosis (MS) and 38 healthy controls. We used T2-relaxation with combined GRadient And Spin Echoes (GRASE) to measure myelin water fraction (MWF-G), multi-component driven equilibrium single pulse observation of T1 and T2 (mcDESPOT) to measure MWF-D, magnetization-transfer imaging to measure magnetization-transfer ratio (MTR), and T1 relaxation to measure quantitative T1 (qT1 ). Using voxelwise Spearman correlations, we tested the correspondence of methods throughout the brain. All four methods showed associations that varied across tissue types; the highest correlations were found between MWF-D and qT1 (median ρ across tissue classes 0.8) and MWF-G and MWF-D (median ρ = 0.59). In eight WM tracts, all measures showed differences (p < 0.05) between MS normal-appearing WM and healthy control WM, with qT1 showing the highest number of different regions (8), followed by MWF-D and MTR (6), and MWF-G (n = 4). Comparing the methods in terms of their statistical sensitivity to MS lesions in WM, MWF-D demonstrated the best accuracy (p < 0.05, after multiple comparison correction). To aid future power analysis, we provide the average and standard deviation volumes of the four techniques, estimated from the healthy control sample.

Breakfast Omission Reduces Subsequent Resistance Exercise Performance.

Bin Naharudin, MN, Yusof, A, Shaw, H, Stockton, M, Clayton, DJ, and James, LJ. Breakfast omission reduces subsequent resistance exercise performance. J Strength Cond Res 33(7): 1766-1772, 2019-Although much research has examined the influence of morning carbohydrate intake (i.e., breakfast) on endurance performance, little is known about its effects on performance in resistance-type exercise. Sixteen resistance-trained men (age 23 ± 4 years, body mass 77.56 ± 7.13 kg, and height 1.75 ± 0.04 m) who regularly (≥3 day/wk) consumed breakfast completed this study. After assessment of 10 repetition maximum (10RM) and familiarization process, subjects completed 2 randomized trials. After an overnight fast, subjects consumed either a typical breakfast meal (containing 1.5 g of carbohydrate/kg; breakfast consumption [BC]) or a water-only breakfast (breakfast omission [BO]). Two hours later, subjects performed 4 sets to failure of back squat and bench press at 90% of their 10RM. Sensations of hunger, fullness, desire to eat, and prospective food consumption were collected before, as well as immediately, 1 hour and 2 hours after BC/BO using 100-mm visual analogue scales. Total repetitions completed were lower during BO for both back squat (BO: 58 ± 11 repetitions; BC: 68 ± 14 repetitions; effect size [ES] = 0.98; p < 0.001) and bench press (BO: 38 ± 5 repetitions; BC: 40 ± 5 repetitions; ES = 1.06; p < 0.001). Fullness was greater, whereas hunger, desire to eat, and prospective food consumption were lower after a meal for BC compared with BO (p < 0.001). The results of this study demonstrate that omission of a pre-exercise breakfast might impair resistance exercise performance in habitual breakfast consumers. Therefore, consumption of a high-carbohydrate meal before resistance exercise might be a prudent strategy to help maximize performance.

24-h severe energy restriction impairs postprandial glycaemic control in young, lean males.

Intermittent energy restriction (IER) involves short periods of severe energy restriction interspersed with periods of adequate energy intake, and can induce weight loss. Insulin sensitivity is impaired by short-term, complete energy restriction, but the effects of IER are not well known. In randomised order, fourteen lean men (age: 25 (sd 4) years; BMI: 24 (sd 2) kg/m2; body fat: 17 (4) %) consumed 24-h diets providing 100 % (10 441 (sd 812) kJ; energy balance (EB)) or 25 % (2622 (sd 204) kJ; energy restriction (ER)) of estimated energy requirements, followed by an oral glucose tolerance test (OGTT; 75 g of glucose drink) after fasting overnight. Plasma/serum glucose, insulin, NEFA, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and fibroblast growth factor 21 (FGF21) were assessed before and after (0 h) each 24-h dietary intervention, and throughout the 2-h OGTT. Homoeostatic model assessment of insulin resistance (HOMA2-IR) assessed the fasted response and incremental AUC (iAUC) or total AUC (tAUC) were calculated during the OGTT. At 0 h, HOMA2-IR was 23 % lower after ER compared with EB (P<0·05). During the OGTT, serum glucose iAUC (P<0·001), serum insulin iAUC (P<0·05) and plasma NEFA tAUC (P<0·01) were greater during ER, but GLP-1 (P=0·161), GIP (P=0·473) and FGF21 (P=0·497) tAUC were similar between trials. These results demonstrate that severe energy restriction acutely impairs postprandial glycaemic control in lean men, despite reducing HOMA2-IR. Chronic intervention studies are required to elucidate the long-term effects of IER on indices of insulin sensitivity, particularly in the absence of weight loss.

Movement and structure of mitochondria in oligodendrocytes and their myelin sheaths.

Mitochondria play several crucial roles in the life of oligodendrocytes. During development of the myelin sheath they are essential providers of carbon skeletons and energy for lipid synthesis. During normal brain function their consumption of pyruvate will be a key determinant of how much lactate is available for oligodendrocytes to export to power axonal function. Finally, during calcium-overload induced pathology, as occurs in ischemia, mitochondria may buffer calcium or induce apoptosis. Despite their important functions, very little is known of the properties of oligodendrocyte mitochondria, and mitochondria have never been observed in the myelin sheaths. We have now used targeted expression of fluorescent mitochondrial markers to characterize the location and movement of mitochondria within oligodendrocytes. We show for the first time that mitochondria are able to enter and move within the myelin sheath. Within the myelin sheath the highest number of mitochondria was in the cytoplasmic ridges along the sheath. Mitochondria moved more slowly than in neurons and, in contrast to their behavior in neurons and astrocytes, their movement was increased rather than inhibited by glutamate activating NMDA receptors. By electron microscopy we show that myelin sheath mitochondria have a low surface area of cristae, which suggests a low ATP production. These data specify fundamental properties of the oxidative phosphorylation system in oligodendrocytes, the glial cells that enhance cognition by speeding action potential propagation and provide metabolic support to axons.

The genomics of memory and learning in songbirds.

Songbirds have unique value as a model for memory and learning. In their natural social life, they communicate through vocalizations that they must learn to produce and recognize. Song communication elicits abrupt changes in gene expression in regions of the forebrain responsible for song perception and production--what is the functional significance of this genomic response? For 20 years, the focus of research was on just a few genes [primarily ZENK, now known as egr1 (early gene response 1)]. Recently, however, DNA microarrays have been developed and applied to songbird behavioral research, and in 2010 the initial draft assembly of the zebra finch genome was published. Together, these new data reveal that the genomic involvement in song processing is far more complex than anticipated. The concepts of neurogenomic computation and biological embedding are introduced as frameworks for future research.

A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk.

Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 × 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 × 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.