Structural subnetwork evolution across the life-span: rich-club, feeder, seeder

The impact of developmental and aging processes on brain connectivity and the connectome has been widely studied. Network theoretical measures and certain topological principles are computed from the entire brain, however there is a need to separate and understand the underlying subnetworks which contribute towards these observed holistic connectomic alterations. One organizational principle is the rich-club - a core subnetwork of brain regions that are strongly connected, forming a high-cost, high-capacity backbone that is critical for effective communication in the network. Investigations primarily focus on its alterations with disease and age. Here, we present a systematic analysis of not only the rich-club, but also other subnetworks derived from this backbone - namely feeder and seeder subnetworks. Our analysis is applied to structural connectomes in a normal cohort from a large, publicly available lifespan study. We demonstrate changes in rich-club membership with age alongside a shift in importance from 'peripheral' seeder to feeder subnetworks. Our results show a refinement within the rich-club structure (increase in transitivity and betweenness centrality), as well as increased efficiency in the feeder subnetwork and decreased measures of network integration and segregation in the seeder subnetwork. These results demonstrate the different developmental patterns when analyzing the connectome stratified according to its rich-club and the potential of utilizing this subnetwork analysis to reveal the evolution of brain architectural alterations across the life-span

Optimizing Functional Network Representation of Multivariate Time Series

By combining complex network theory and data mining techniques, we provide objective criteria for optimization of the functional network representation of generic multivariate time series. In particular, we propose a method for the principled selection of the threshold value for functional network reconstruction from raw data, and for proper identification of the network's indicators that unveil the most discriminative information on the system for classification purposes. We illustrate our method by analysing networks of functional brain activity of healthy subjects, and patients suffering from Mild Cognitive Impairment, an intermediate stage between the expected cognitive decline of normal aging and the more pronounced decline of dementia. We discuss extensions of the scope of the proposed methodology to network engineering purposes, and to other data mining tasks

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Translations equations to compare ActiGraph GT3X and Actical accelerometers activity counts

Background: This study aimed to develop a translation equation to enable comparison between Actical and ActiGraph GT3X accelerometer counts recorded minute by minute. Methods: Five males and five females of variable height, weight, body mass index and age participated in this investigation. Participants simultaneously wore an Actical and an ActiGraph accelerometer for two days. Conversion algorithms and R2 were calculated day by day for each subject between the omnidirectional Actical and three different ActiGraph (three-dimensional) outputs: 1) vertical direction, 2) combined vector, and 3) a custom vector. Three conversion algorithms suitable for minute/minute conversions were then calculated from the full data set. Results: The vertical ActiGraph activity counts demonstrated the closest relationship with the Actical, with consistent moderate to strong conversions using the algorithm: y = 0.905x, in the day by day data (R2 range: 0.514 to 0.989 and average: 0.822) and full data set (R2 = 0.865). Conclusions: The Actical is most sensitive to accelerations in the vertical direction, and does not closely correlate with three-dimensional ActiGraph output. Minute by minute conversions between the Actical and ActiGraphvertical component can be confidently performed between data sets and might allow further synthesis of information between studies

Validity of the international physical activity questionnaire and the Singapore prospective study program physical activity questionnaire in a multiethnic urban Asian population

<p>Abstract</p> <p>Background</p> <p>Physical activity patterns of a population remain mostly assessed by the questionnaires. However, few physical activity questionnaires have been validated in Asian populations. We previously utilized a combination of different questionnaires to assess leisure time, transportation, occupational and household physical activity in the Singapore Prospective Study Program (SP2). The International Physical Activity Questionnaire (IPAQ) has been developed for a similar purpose. In this study, we compared estimates from these two questionnaires with an objective measure of physical activity in a multi-ethnic Asian population.</p> <p>Methods</p> <p>Physical activity was measured in 152 Chinese, Malay and Asian Indian adults using an accelerometer over five consecutive days, including a weekend. Participants completed both the physical activity questionnaire in SP2 (SP2PAQ) and IPAQ long form. 43subjects underwent a second set of measurements on average 6 months later to assess reproducibility of the questionnaires and the accelerometer measurements. Spearman correlations were used to evaluate validity and reproducibility and correlations for validity were corrected for within-person variation of accelerometer measurements. Agreement between the questionnaires and the accelerometer measurements was also evaluated using Bland Altman plots.</p> <p>Results</p> <p>The corrected correlation with accelerometer estimates of energy expenditure from physical activity was better for the SP2PAQ (vigorous activity: r = 0.73; moderate activity: r = 0.27) than for the IPAQ (vigorous activity: r = 0.31; moderate activity: r = 0.15). For moderate activity, the corrected correlation between SP2PAQ and the accelerometer was higher for Chinese (r = 0.38) and Malays (r = 0.57) than for Indians (r = -0.09). Both questionnaires overestimated energy expenditure from physical activity to a greater extent at higher levels of physical activity than at lower levels of physical activity. The reproducibility for moderate activity (accelerometer: r = 0.68; IPAQ: r = 0.58; SP2PAQ: r = 0.55) and vigorous activity (accelerometer: 0.52; IPAQ: r = 0.38; SP2PAQ: r = 0.75) was moderate to high for all instruments.</p> <p>Conclusion</p> <p>The agreement between IPAQ and accelerometer measurements of energy expenditure from physical activity was poor in our Asian study population. The SP2PAQ showed good validity and reproducibility for vigorous activity, but performed less well for moderate activity particularly in Indians. Further effort is needed to develop questionnaires that better capture moderate activity in Asian populations.</p

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

A Model for the Roll-Out of Comprehensive Adult Male Circumcision Services in African Low-Income Settings of High HIV Incidence: The ANRS 12126 Bophelo Pele Project

Bertrand Auvert and colleagues describe the large-scale roll-out of adult male circumcision through a program in South Africa

The publics' understanding of daily caloric recommendations and their perceptions of calorie posting in chain restaurants

<p>Abstract</p> <p>Background</p> <p>Calorie posting in chain restaurants has received increasing attention as a policy lever to reduce energy intake. Little research has assessed consumer understanding of overall daily energy requirements or perceived effectiveness of calorie posting.</p> <p>Methods</p> <p>A phone survey was conducted from May 1 through 17, 2009 with 663 randomly selected, nationally-representative adults aged 18 and older, including an oversample of Blacks and Hispanics in the United States. To examine differences in responses by race and ethnicity (White, Black, and Hispanic) and gender, we compared responses by conducting chi-squared tests for differences in proportions.</p> <p>Results</p> <p>We found that most Americans were knowledgeable about energy requirements for moderately active men (78%) and women (69%), but underestimated energy requirements for inactive adults (60%). Whites had significantly higher caloric literacy and confidence about their caloric knowledge than Blacks and Hispanics (p < 0.05). As compared to their counterparts, Blacks, Hispanics and women reported a significantly higher likelihood of eating at a chain restaurant and of selecting lower calorie foods where caloric information was posted. Most Americans favored the government requiring chain restaurants to post calorie information on menus at the point of purchase (68%). Support for government mandated calorie posting in chain restaurants was significantly higher among Blacks, Hispanics and women as compared to their counterparts. The public was divided about the mode of caloric information that would best help them make a lower calorie decision; a third favored number of calories (35%) which is the current standard mode of presenting caloric information in chain restaurants, a third favored a physical activity equivalent (26%), and a third favored percentage of total energy intake (39%).</p> <p>Conclusion</p> <p>Mandating calorie posting in chain restaurants may be a useful policy tool for promoting energy balance, particularly among Blacks, Hispanics and women who have higher obesity risk.</p