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High-amplitude co-fluctuations in cortical activity drive resting-state functional connectivity
No full textResting-state functional connectivity is used throughout neuroscience to study brain organization and to generate biomarkers of development, disease, and cognition. The processes that give rise to correlated activity are, however, poorly understood. Here, we decompose resting-state functional connectivity using a “temporal unwrapping” procedure to assess the contributions of moment-to-moment activity co-fluctuations to the overall connectivity pattern. This approach temporally resolves functional connectivity at a timescale of single frames, which enables us to make direct comparisons of co-fluctuations of network organization with fluctuations in the BOLD time series. We show that, surprisingly, only a small fraction of frames exhibiting the strongest co-fluctuation amplitude are required to explain a significant fraction of variance in the overall pattern of connection weights as well as the network’s modular structure. These frames coincide with frames of high BOLD activity amplitude, corresponding to activity patterns that are remarkably consistent across individuals and identify fluctuations in default mode and control network activity as the primary driver of resting-state functional connectivity. Finally, we demonstrate that co-fluctuation amplitude synchronizes across subjects during movie-watching and that high-amplitude frames carry detailed information about individual subjects (whereas low-amplitude frames carry little). Our approach reveals fine-scale temporal structure of resting-state functional connectivity, and discloses that frame-wise contributions vary across time. These observations illuminate the relation of brain activity to functional connectivity and open a number of new directions for future research
The Association between Sleep Duration and Metabolic Syndrome: The NHANES 2013/2014
No full textBackground: We aimed to assess the association of sleep with metabolic syndrome in the 2013/2014 National Health and Nutrition Examination Survey (NHANES). Methods: Sample size included 2737 out of 2013 and 2014 NHANES surveys. Cross-sectional study of metabolic syndrome and sleep duration was conducted. Metabolic syndrome was defined according to NCEP ATPIII (National Cholesterol Education Program Adult Treatment Panel III) criteria. Metabolic syndrome severity score was calculated based on actual measurement of each component, adjusted for sex and race. The generalized additive model (GAM) was built to assess the smooth relationship between metabolic syndrome/metabolic syndrome severity score and sleep duration. Adjustment of models were done for age, sex, race, and sitting time. The value of effective degree of freedom (EDF) formed by the GAM model shows the degree of curvature of the relationship. A value of 1 for EDF is translated as the linear shape of relationship. Values larger than one denote a more complex relationship between the response variable and the predicting one. Results: There was a U-shaped association between sleep duration and metabolic syndrome in univariable GAM (EDF = 2.43, = 0.06) and multivariable GAM (EDF = 2.03, = 0.20). The lowest risk of metabolic syndrome was observed in people sleeping 7 hours/night. There was a significant U-shaped association between sleep duration and metabolic syndrome severity score in multivariable GAM (EDF = 2.94, = 0.0004). Similarly, the lowest mean metabolic syndrome severity score was observed in people sleeping 7 hours/night. There was an effect modification of sex and sleep duration indicating strong U-shaped relationship of metabolic syndrome severity score and sleep duration in women (EDF = 3.43, = 0.00002) and semi-linear association in men (EDF = 1.76, = 0.04). Conclusion: Short and long sleep duration was associated with higher risk of metabolic syndrome and higher scores of metabolic syndrome severity score in women. Short sleep duration was associated with higher risk of metabolic syndrome and higher scores of metabolic syndrome severity score in men
Dietary choline and betaine intakes and risk of total and lethal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study
No full textPurpose: Two prior cohort studies suggested that choline, but not betaine intake, is associated with an increased risk of advanced prostate cancer (PCa). Given that evidence remains limited, we evaluated whether intakes of choline and derivative betaine are associated with total and lethal PCa risk and PCa death in men with PCa. Methods: We included 6,528 men (24.4% African American) without a cancer diagnosis at baseline (1987–1989) followed through 2012. Dietary intake was assessed using a food frequency questionnaire coupled with a nutrient database. We used Cox proportional hazards regression to estimate hazards ratios (HRs) and 95% confidence intervals (CIs) of total and lethal PCa risk overall and by race. Results: Choline intake was not associated with total ( = 811) or lethal ( = 95) PCa risk overall or by race. Betaine intake was inversely associated with lethal (tertile 3 vs 1, HR 0.59, 95% CI 0.35–1.00, trend = 0.04), but not total PCa risk; patterns for lethal PCa were similar by race. Neither nutrient was associated with PCa death in men with PCa. Conclusions: Choline intake was not associated with total or lethal PCa or with PCa death in men with PCa. Betaine intake was inversely associated with lethal, but not total PCa risk or with PCa death in men with PCa. Our results do not support the hypothesis that higher choline intake increases lethal PCa risk, but do suggest that higher betaine intake may be associated with lower lethal PCa risk. Further investigation with a larger number of lethal cases is needed
On the number of pancake stacks requiring four flips to be sorted
No full textUsing existing classification results for the 7- and 8-cycles in the pancake graph, we determine the number of permutations that require 4 pancake flips (prefix reversals) to be sorted. A similar characterization of the 8-cycles in the burnt pancake graph, due to the authors, is used to derive a formula for the number of signed permutations requiring 4 (burnt) pancake flips to be sorted. We furthermore provide an analogous characterization of the 9-cycles in the burnt pancake graph. Finally we present numerical evidence that polynomial formulae exist giving the number of signed permutations that require flips to be sorted, with 5≤ ≤9
Differential activity of BPA, BPAF and BPC on zebrafish estrogen receptors in vitro and in vivo
No full textThe high volume production compound bisphenol A (BPA) is of environmental concern largely because of its estrogenic activity. Consequently, BPA analogues have been synthesized to be considered as replacement molecules for BPA. These analogues need to be thoroughly evaluated for their estrogenic activity. Here, we combined mechanism zebrafish-based assays to examine estrogenic and anti-estrogenic activities of BPA and two of its analogues, bisphenol AF (BPAF) and bisphenol C (BPC) in vitro and in vivo. In vitro reporter cell lines were used to investigate agonistic and antagonistic effects of the three bisphenols on the three zebrafish estrogen receptors. The transgenic Tg(5 × ERE:GFP) and Cyp19a1b-GFP zebrafish lines were then used to analyze estrogenic and anti-estrogenic responses of the three bisphenols in vivo. BPA, BPAF and BPC were agonists with different potencies for the three zebrafish estrogen receptors in vitro. The potent zfERα-mediated activity of BPA and BPAF in vitro resulted in vivo by activation of GFP expression in zebrafish larvae in the heart (zfERα-dependent) at lower concentrations, and in the liver (zfERβ-dependent) at higher concentrations. BPC induced zfERβ-mediated luciferase expression in vitro, and the zfERβ agonism led to activation of GFP expression in the liver and the brain in vivo. In addition, BPC acted as a full antagonist on zfERα, and completely inhibited estrogen-induced GFP expression in the heart of the zebrafish larvae. To summarize, applying a combination of zebrafish-based in vitro and in vivo methods to evaluate bisphenol analogues for estrogenic activity will facilitate the prioritization of these chemicals for further analysis in higher vertebrates as well as the risk assessment in humans
Chemotherapy-induced cachexia dysregulates hypothalamic and systemic lipoamines and is attenuated by cannabigerol
No full textBackground: Muscle wasting, anorexia, and metabolic dysregulation are common side‐effects of cytotoxic chemotherapy, having a dose‐limiting effect on treatment efficacy, and compromising quality of life and mortality. Extracts of Cannabis sativa, and analogues of the major phytocannabinoid Δ9‐tetrahydrocannabinol, have been used to ameliorate chemotherapy‐induced appetite loss and nausea for decades. However, psychoactive side‐effects limit their clinical utility, and they have little efficacy against weight loss. We recently established that the non‐psychoactive phytocannabinoid cannabigerol (CBG) stimulates appetite in healthy rats, without neuromotor side‐effects. The present study assessed whether CBG attenuates anorexia and/or other cachectic effects induced by the broad‐spectrum chemotherapy agent cisplatin. Methods: An acute cachectic phenotype was induced in adult male Lister‐hooded rats by 6 mg/kg (i.p.) cisplatin. In total 66 rats were randomly allocated to groups receiving vehicle only, cisplatin only, or cisplatin and 60 or 120 mg/kg CBG (po, b.i.d.). Feeding behavior, bodyweight and locomotor activity were recorded for 72 hours, at which point rats were sacrificed for post‐mortem analyses. Myofibre atrophy, protein synthesis and autophagy dysregulation were assessed in skeletal muscle, plasma metabolic profiles were obtained by untargeted 1H‐NMR metabonomics, and levels of endocannabinoid‐like lipoamines quantified in plasma and hypothalami by targeted HPLC‐MS/MS lipidomics. Results: CBG (120 mg/kg) modestly increased food intake, predominantly at 36‐60hrs (p<0.05), and robustly attenuated cisplatin‐induced weight loss from 6.3% to 2.6% at 72hrs (p<0.01). Cisplatin‐induced skeletal muscle atrophy was associated with elevated plasma corticosterone (3.7 vs 13.1ng/ml, p<0.01), observed selectively in MHC type IIx (p<0.05) and IIb (p<0.0005) fibres, and was reversed by pharmacological rescue of dysregulated Akt/S6‐mediated protein synthesis and autophagy processes. Plasma metabonomic analysis revealed cisplatin administration produced a wide‐ranging aberrant metabolic phenotype (Q2Ŷ=0.5380, p=0.001), involving alterations to glucose, amino acid, choline and lipid metabolism, citrate cycle, gut microbiome function, and nephrotoxicity, which were partially normalized by CBG treatment (Q2Ŷ=0.2345, p=0.01). Lipidomic analysis of hypothalami and plasma revealed extensive cisplatin‐induced dysregulation of central and peripheral lipoamines (29/79 and 11/26 screened, respectively), including reversible elevations in systemic N‐acyl glycine concentrations which were negatively associated with the anti‐cachectic effects of CBG treatment. Conclusions: Endocannabinoid‐like lipoamines may have hitherto unrecognized roles in the metabolic side‐effects associated with chemotherapy, with the N‐acyl glycine subfamily in particular identified as a potential therapeutic target and/or biomarker of anabolic interventions. CBG‐based treatments may represent a novel therapeutic option for chemotherapy‐induced cachexia, warranting investigation in tumour‐bearing cachexia models
Within-subject variability in human retinal nerve fiber bundle width
No full textWith the growing availability of high-resolution imaging there has been increased interest in developing new metrics for integrity of the retinal nerve fiber layer. In particular, it has been suggested that measurement of width of retinal nerve fiber bundles (RNFBs) may be useful in glaucoma, due to low between-subject variability in mean RNFB width. However, there have also been reports of substantial within-subject variability in the width of individual RNFBs. To assess within-subject variability as a potential source of selection bias in measurements of RNFB width, we used an adaptive optics scanning laser ophthalmoscope (AOSLO) to measure widths of individual RNFBs in one eye each of 11 young adults in good ocular health. In a pilot study we analyzed a large AOSLO image of RNFL in one participant then, based on those findings, in the main study we used AOSLO to image a smaller region in 10 additional healthy young adults. The pilot study of one eye found RNFB widths ranging from 10 μm to 44 μm. This suggested that biological variability was too high for measuring small changes arising from disease processes. This was confirmed in measurements of 10 eyes in the main study, RNFB widths ranged from 9 μm to 55 μm and every eye had large within-subject variability (exceeding 19 μm in all eyes) in RNFB width for nearby bundles. The within-subject variability in RNFB width, as well as variation in the width of single RNFBs over relatively short distances (<300 um) depending on the precise location of measurement, suggests that bundle width measurements would be highly susceptible to selection bias and therefore of limited clinical use
Age-related changes in eye lens biomechanics, morphology, refractive index and transparency
No full textLife-long eye lens function requires an appropriate gradient refractive index, biomechanical integrity and transparency. We conducted an extensive study of wild-type mouse lenses 1-30 months of age to define common age-related changes. Biomechanical testing and morphometrics revealed an increase in lens volume and stiffness with age. Lens capsule thickness and peripheral fiber cell widths increased between 2 to 4 months of age but not further, and thus, cannot account for significant age-dependent increases in lens stiffness after 4 months. In lenses from mice older than 12 months, we routinely observed cataracts due to changes in cell structure, with anterior cataracts due to incomplete suture closure and a cortical ring cataract corresponding to a zone of compaction in cortical lens fiber cells. Refractive index measurements showed a rapid growth in peak refractive index between 1 to 6 months of age, and the area of highest refractive index is correlated with increases in lens nucleus size with age. These data provide a comprehensive overview of age-related changes in murine lenses, including lens size, stiffness, nuclear fraction, refractive index, transparency, capsule thickness and cell structure. Our results suggest similarities between murine and primate lenses and provide a baseline for future lens aging studies
Oh Brother Where Art Thou?: The Struggles of African American Males in the Global Economy of the Information Age
No full textIn the late 1980s, William Wilson first argued that widespread economic transitions had altered the socioeconomic structure of American inner cities to the detriment of African Americans. Wilson identified declines in manufacturing work and its replacement with poorly compensated service-sector work as driving racial segregation and leaving African Americans jobless, poor, and alienated from American society. These transitions were particularly problematic for African American men because manufacturing work was their primary gateway to middle- class employment, while African American women had already focused more on service work
Correlated Depletion and Dilution of Lithium and Beryllium Revealed by Subgiants in M67
No full textThe surface content of lithium (Li) and beryllium (Be) provides insight into the mixing and circulation mechanisms in stellar interiors. The old open cluster, M67, has been well-studied for Li abundances in both main-sequence and evolved stars. The Be abundances give us a probe to a deeper level in stars. We have taken high-resolution spectra with Keck I with HIRES to determine Be abundances along the subgiant branch of M67, where there are dramatic depletions of Li. These subgiants range in mass from 1.26 to 1.32 M and have evolved from main-sequence stars that would have occupied the region of the Li–Be dip found in younger clusters. Lithium abundances have been adjusted to the same scale for 103 stars in M67 by Pace et al. The more massive stars—now the coolest and furthest-evolved from the main sequence—show a drop in Li by a factor of 400 across the subgiant branch. Our new Be abundances also show a decline, but by a factor of ~50. The two elements decline together with Li showing a steeper decline in these subgiants than it does in the Li–Be dip stars. The relative decline in Be abundance compared to Li is remarkably well fit by the models of Sills & Deliyannis, made specifically for the subgiants in M67. Those models include the effects of mixing induced by stellar rotation. These M67 subgiants show the effects of both main-sequence depletion and post-main-sequence dilution of both Li and Be