bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal fish oil supplementation during lactation is associated with reduced height at 13 years of age and higher blood pressure in boys only
Authors: Lauritzen L. , Eriksen S. E. , Hjorth M. F. , Nielsen M. S. , Olsen S. F. , Stark K. D. , Michaelsen K. F. , Damsgaard C. T.
Published: January 2017

Dietary long-chain n-3 PUFA (n-3 LCPUFA) in infancy may have long-term effects on lifestyle disease risk. The present follow-up study investigated whether maternal fish oil (FO) supplementation during lactation affected growth and blood pressure in adolescents and whether the effects differed between boys and girls. Mother–infant pairs (n 103) completed a randomised controlled trial with FO (1·5 g/d n-3 LCPUFA) or olive oil (OO) supplements during the first 4 months of lactation; forty-seven mother–infant pairs with high fish intake were followed-up for 4 months as the reference group. We also followed-up 100 children with assessment of growth, blood pressure, diet by FFQ and physical activity by 7-d accelerometry at 13·5 (sd 0·4) years of age. Dried whole-blood fatty acid composition was analysed in a subgroup (n 49). At 13 years of age, whole-blood n-3 LCPUFA, diet, physical activity and body composition did not differ between the three groups. The children from the FO group were 3·4 (95 % CI 0·2, 6·6) cm shorter (P=0·035) than those from the OO group, and tended to have less advanced puberty (P=0·068), which explained the difference in height. There was a sex-specific effect on diastolic blood pressure (Psex×group=0·020), which was driven by a 3·9 (95 % CI 0·2, 7·5) mmHg higher diastolic blood pressure in the FO compared with the OO group among boys only (P=0·041). Our results indicate that early n-3 LCPUFA intake may reduce height in early adolescence due to a delay in pubertal maturation and increase blood pressure specifically in boys, thereby tending to counteract existing sex differences.
The Gendering of Dynastic Memory: Burial Choices of the Howards, 1485–1559
Authors: CLARK NICOLA
Published: January 2017

Scholarship by Barbara Harris, James Daybell and others has recently highlighted the role played by elite women as custodians of dynastic memory in early modern England. The Dissolution of the Monasteries interrupted the commemorative process and constituted a threat to the mausoleums of the elite. Moving or rebuilding tombs represented, to some extent, a decision to remake or even to rewrite the family's history, a process which it is often assumed was at this time controlled by men. This article, however, through the example of the Howard family, demonstrates that women were equally involved; it investigates why this was so and the mechanics of the processs.
Obligation and Sovereign Virtue in Hobbes'sLeviathan
Authors: Hoye J. Matthew
Published: January 2017

Debates regarding obligation in Hobbes have turned on either natural right or natural law interpretations. Both interpretations tend to take up the question of obligation from the perspective of teaching those who contend “for too great Liberty” “how to obey.” But Hobbes also has a second audience, and a second goal in mind: those who contend “for too much Authority” must be taught “how to govern.” From that perspective, a different discussion of obligation emerges. What is revealed is a contiguous set of reflections inLeviathanthat pivot on the character of the sovereign and the citizens’ judgment thereof, all of which inform effective obligation and have little in common with received interpretations of obligation. It further reveals a relationship between the failure to manifest sovereign virtue and the natural punishment of pusillanimous and barbaric sovereigns. That is, it speaks to a sovereign virtue ethic inLeviathan.
John Stuart Mill, Children's Liberty, and the Unraveling of Autonomy
Authors: Stanley Sharon
Published: January 2017

InOn Liberty, John Stuart Mill famously excluded children and so-called barbarians from his otherwise broad grant of liberty to human beings. While many scholars have analyzed and criticized the barbarian exclusion, little attention has been focused on the denial of liberty to children. This article argues that Mill's theory of liberty rests on an untenable dividing line between childhood dependence and adult autonomy. The processes of discipline and socialization to which children are subject render them incapable as adults of achieving the kind of autonomy that Mill prescribes. Using relational autonomy as an alternative to Mill's model of autonomy, I propose that we should neither flatly deny liberty to children nor present absolute independence as a normative ideal for adults.
Assessing the validity and reliability of measurements when evaluating public policy
Authors: Crepaz Michele , Chari Raj
Published: January 2017

A substantial aspect of scientific research involves linking concepts to observations using measurements. This exercise has raised questions among researchers of whether or not measurements “truly” and “reliably” capture ideas and observations. We address this question by setting out a methodological standard on how to assess the validity and reliability of measurements. We do this by examining measurements that evaluate public policy, arguing that this topic is gaining increasing attention from political science researchers and policymakers. The analysis concerns measurements of the level of transparency and accountability of lobbying laws, central to recent regulatory policy research. We conduct convergent validation, content validation and reproducibility tests on four indices applied to 13 regulations found worldwide. By doing so, the article provides scholars with an evaluation of measurements of lobbying laws’ robustness, while offering methodological and theoretical lessons of value to larger regulatory and public policy scholarship.
ESTIMATING STRUCTURAL PARAMETERS IN REGRESSION MODELS WITH ADAPTIVE LEARNING
Authors: Christopeit Norbert , Massmann Michael
Published: January 2017

This paper examines the ordinary least squares (OLS) estimator of the structural parameters in a simple macroeconomic model in which agents are boundedly rational and use an adaptive learning rule to form expectations of the endogenous variable. The popularity of learning models has recently increased amongst applied economists and policy makers who seek to estimate them empirically. Yet the econometrics of learning models is largely uncharted territory. We consider two prominent learning algorithms, namely constant gain and decreasing gain learning. For each of the two learning rules, our analysis proceeds in two stages. First, the paper derives the asymptotic properties of agents’ expectations. At the second stage, the paper derives the asymptotics of OLS in the structural model, taking the first stage learning dynamics as given. In the case of constant gain learning, the structural model effectively amounts to a stationary, cointegrating, or co-explosiveness regression. With decreasing gain learning, the regressors are asymptotically collinear such that OLS does not satisfy, in general, the Grenander conditions for consistent estimability. Nevertheless, this paper shows that the OLS estimator remains consistent in all models considered. It also shows, however, that its asymptotic distribution, and hence any inference based upon it, may be nonstandard.
Minding the gaps: literacy enhances lexical segmentation in children learning to read
Authors: HAVRON NAOMI , ARNON INBAL
Published: January 2017

Can emergent literacy impact the size of the linguistic units children attend to? We examined children's ability to segment multiword sequences before and after they learned to read, in order to disentangle the effect of literacy and age on segmentation. We found that early readers were better at segmenting multiword units (after controlling for age, cognitive, and linguistic variables), and that improvement in literacy skills between the two sessions predicted improvement in segmentation abilities. Together, these findings suggest that literacy acquisition, rather than age, enhanced segmentation. We discuss implications for models of language learning.
Lie theory of finite simple groups and the Roth property
Authors: LÓPEZ PEÑA J. , MAJID S. , RIETSCH K.
Published: January 2017

In noncommutative geometry a ‘Lie algebra’ or bidirectional bicovariant differential calculus on a finite group is provided by a choice of an ad-stable generating subset$\mathcal{C}$stable under inversion. We study the associated Killing formK. For the universal calculus associated to$\mathcal{C}$=G\ {e} we show that the magnitude$\mu=\sum_{a,b\in\mathcal{C}}(K^{-1})_{a,b}$of the Killing form is defined for all finite groups (even whenKis not invertible) and that a finite group is Roth, meaning its conjugation representation contains every irreducible,iffμ ≠ 1/(N− 1) whereNis the number of conjugacy classes. We show further that the Killing form is invertible in the Roth case, and that the Killing form restricted to the (N− 1)-dimensional subspace of invariant vectors is invertibleiffthe finite group is an almost-Roth group (meaning its conjugation representation has at most one missing irreducible). It is known [9, 10] that most nonabelian finite simple groups are Roth and that all are almost Roth. At the other extreme from the universal calculus we prove that the 2-cycles conjugacy class in anySnhas invertible Killing form, and the same for the generating conjugacy classes in the case of the dihedral groupsD2nwithnodd. We verify invertibility of the Killing forms of all real conjugacy classes in all nonabelian finite simple groups to order 75,000, by computer, and we conjecture this to extend to all nonabelian finite simple groups.
Prevalence of tuberculosis infection in healthcare workers of the public hospital network in Medellín, Colombia: a Bayesian approach
Authors: OCHOA J. , LEÓN A. L. , RAMÍREZ I. C. , LOPERA C. M. , BERNAL E. , ARBELÁEZ M. P.
Published: January 2017

A latent tuberculosis infection (LTBI) prevalence survey was conducted using tuberculin skin test (TST) and Quantiferon test (QFT) in 1218 healthcare workers (HCWs) in Medellín, Colombia. In order to improve the prevalence estimates, a latent class model was built using a Bayesian approach with informative priors on the sensitivity and specificity of the TST. The proportion of concordant results (TST+,QFT+) was 41% and the discordant results contributed 27%. The marginal estimate of the prevalence P(LTBI+) was 62·1% [95% credible interval (CrI) 53·0–68·2]. The probability of LTBI+ given positive results for both tests was 99·6% (95% CrI 98·1–99·9). Sensitivity was 88·5 for TST and 74·3 for QFT, and specificity was 87·8 for TST and 97·6 for QFT. A high LTBI prevalence was found in HCWs with time-accumulated exposure in hospitals that lack control plans. In a context of intermediate tuberculosis (TB) incidence it is recommended to use only one test (either QFT or TST) in prevalence surveys or as pre-employment tests. Results will be useful to help implement TB infection control plans in hospitals where HCWs may be repeatedly exposed to unnoticed TB patients, and to inform the design of TB control policies.
Marital stress and children's externalizing behavior as predictors of mothers’ and fathers’ parenting
Authors: Elam Kit K. , Chassin Laurie , Eisenberg Nancy , Spinrad Tracy L.
Published: January 2017

Previous research suggests that mothers’ and fathers’ parenting may be differentially influenced by marital and child factors within the family. Some research indicates that marital stress is more influential in fathers’ than mothers’ parenting, whereas other research shows that children's difficult behavior preferentially affects mothers’ parenting. The present study examined marital stress and children's externalizing behavior in middle childhood as predictors of mothers’ versus fathers’ consistency, monitoring, and support and care in early adolescence, and the subsequent associations of these parenting behaviors with externalizing behavior 1.5 years later. Pathways were examined within a longitudinal mediation model testing for moderation by parent gender (N= 276 mothers,N= 229 fathers). Children's externalizing behavior in middle childhood was found to more strongly inversely predict mothers’ versus fathers’ monitoring in early adolescence. In contrast, marital stress more strongly predicted low monitoring for fathers than for mothers. Regardless of parent gender, marital stress predicted lower levels of parental consistency, and children's externalizing behavior predicted lower levels of parental support. Mothers’ monitoring and fathers’ support in early adolescence predicted lower levels of externalizing behavior 1.5 years later. The results are discussed with respect to family transactions relative to parent gender and implications for intervention.
Novel foraging by wintering Siberian CranesLeucogeranus leucogeranusat China’s Poyang Lake indicates broader changes in the ecosystem and raises new challenges for a critically endangered species
Authors: BURNHAM JAMES , BARZEN JEB , PIDGEON ANNA M. , SUN BAOTENG , WU JIANDONG , LIU GUANHUA , JIANG HONGXING
Published: January 2017

Following an abnormal flood in 2010 at China’s Poyang Lake, we observed wintering Siberian CranesLeucogeranus leucogeranusswitch from foraging in the shallow-water wetlands they typically use to grassland habitats. These previously undocumented habitat selection patterns raised questions whether differences in crane behaviour such as foraging success existed between the two habitats and how those differences might affect this critically endangered species. Over two winters, we used the density of customary food items (tubers ofVallisneriaspp.) obtained from long-term monitoring efforts, Siberian Cranes flock behaviours, individual foraging success and estimated total flock foraging effort across both habitats. Novel foraging patterns by Siberian Cranes were associated with low densities ofVallisneriatubers across multiple sub-lakes within Poyang Lake National Nature Reserve (PLNR). Foraging success was higher in grasslands than in wetlands in winter 2010–2011, but higher in wetlands following a recovery ofVallisneriain 2011–2012. Subsequent to upland foraging during the winter of 2010–2011, we observed lower juvenile to adult ratio of Siberian Cranes at a fall migratory stopover location in north-eastern China despite indications of average environmental conditions in the nesting areas from 2010 to 2012. While grasslands adjacent to shallow-water habitats may be important refugia for wintering Siberian Cranes whenVallisneriais absent or inaccessible, and should be included in protected areas, multi-year dependence on grasslands for foraging could negatively impact population levels. Eliminating crab farming in protected areas and extending protection to shallow water areas sheltered from flooding by dykes could also help secure high quality foraging habitat under a variety of hydrological regimes. Novel foraging patterns by wintering Siberian Cranes represent a new challenge to the conservation efforts for this species that focus on shallow-water wetlands, and may be indicative of broader changes within Poyang’s ecosystem.
Exploring Alternative Pathways to Social Complexity in the European Iron Age: The Northwestern Iberian Peninsula as a Case Study
Authors: González García Francisco Javier
Published: January 2017

The study of non-hierarchical forms of social organization occupies a prominent place in the European Iron Age research. This paper explores the application of Pierre Clastres political anthropology to the study of the Iron Age. The approach of this study to the Iron Age focuses on the northwest of the Iberian peninsula. It was an area that experienced social changes from 1000 bc to the first century bc–first century ad, from the Bronze Age to the Roman conquest. Using the archaeological record of the northwest Iberian peninsula as a case study, the paper tries to show the potential benefits of applying Clastres’ ideas to the interpretation of European societies from the Iron Age: overcoming, thanks to the application of the concept of non-coercive power, the false and increasingly frequent image of non-hierarchical societies and introducing new ways of explaining social complexity that are not based on economic criteria.
Programming maternal and child overweight and obesity in the context of undernutrition: current evidence and key considerations for low- and middle-income countries
Authors: Jaacks Lindsay M , Kavle Justine , Perry Abigail , Nyaku Albertha
Published: January 2017

The goals of the present targeted review on maternal and child overweight and obesity were to: (i) understand the current situation in low- and middle-income countries (LMIC) with regard to recent trends and context-specific risk factors; and (ii) building off this, identify entry points for leveraging existing undernutrition programmes to address overweight and obesity in LMIC. Trends reveal that overweight and obesity are a growing problem among women and children in LMIC; as in Ghana, Kenya, Niger, Sierra Leone, Tanzania and Zimbabwe, where the prevalence among urban women is approaching 50 %. Four promising entry points were identified: (i) the integration of overweight and obesity into national nutrition plans; (ii) food systems (integration of food and beverage marketing regulations into existing polices on the marketing of breast-milk substitutes and adoption of policies to promote healthy diets); (iii) education systems (integration of nutrition into school curricula with provision of high-quality foods through school feeding programmes); and (iv) health systems (counselling and social and behaviour change communication to improve maternal diet, appropriate gestational weight gain, and optimal infant and young child feeding practices). We conclude by presenting a step-by-step guide for programme officers and policy makers in LMIC with actionable objectives to address overweight and obesity.
Farm level implementation of soil conservation measures: farmers’ beliefs and intentions
Authors: Werner Magdalena , Wauters Erwin , Bijttebier Jo , Steinmann Horst-Henning , Ruysschaert Greet , Knierim Andrea
Published: January 2017

Understanding motivating factors for taking soil conservation measures is seen as key to improving on-farm implementation. However, to date only few on-farm conservation measures have been investigated. The objective of this paper is to investigate the influence of farmers’ subjective beliefs on their intention to apply and actual implementation of cover cropping, with the region of Brandenburg (Germany) as a case. An additional objective was to investigate how these insights can contribute to increase farm level implementation of soil conservation measures. Theory of planned behavior provides an approach to understand human behavior by analyzing farmers’ subjective beliefs. Our results, based on a survey of 96 farmers, show that attitudes (ATTs) and perceived difficulty significantly explain variations in intention to apply cover cropping, with ATTs being generally very positive. We discuss that, in this case, the most effective way to increase on-farm implementation is to decrease the farmers’ perception of difficulty. This can be achieved by providing information to farmers on how to overcome barriers to implementation of conservation measures. In-depth insights into belief structures reveal what kind of information is most useful in the case of cover cropping.
X-band compact dual circularly polarized isoflux antenna for nanosatellite applications
Authors: Arnaud Eric , Menudier Cyrille , Fouany Jamil , Monediere Thierry , Thevenot Marc
Published: January 2017

This paper presents an original solution to design a compact dual circularly polarized isoflux antenna for nanosatellite applications. This kind of antenna has been previously designed in our laboratory, for a single circular polarization. This antenna is composed of a dual circularly polarized feed and a choke horn antenna. This feed is a cross-shaped slot in the ground plane, which provides coupling between a patch and a ring microstrip line with two ports. It is located at the center of a choke horn antenna. The simulated antenna presents an axial ratio <3 dB and a realized gain close to 0 dB over a 400 MHz bandwidth (8.0–8.4 GHz) at the limit of coverage, i.e. 65° whatever the azimuth angle (φ) and the port. A 20 dB matching for each port and 13 dB isolation characteristics between the two ports have been achieved on this bandwidth. It has been realized and successfully measured.
Common mental health problems in rural-to-urban migrant workers in Shenzhen, China: prevalence and risk factors
Authors: Zhong B. L. , Liu T. B. , Chan S. S. M. , Jin D. , Hu C. Y. , Dai J. , Chiu H. F. K.
Published: January 2017

Aims.

Rural-to-urban migrant workers are a large marginalised population in urban China. Prevalence estimates of common mental health problems (CMHPs) in previous studies varied widely and very few studies have investigated migration-related factors of CMHPs in migrant workers. The objective of this study was to determine the prevalence and risk factors of CMHPs among Chinese migrant workers.

Methods.

A random sample of 3031 migrant workers of ten manufacturing factories in Shenzhen, China, completed a standardised questionnaire containing socio-demographic and migration-related variables and the Chinese 12-item General Health Questionnaire (GHQ-12). A GHQ-12 score of three or higher was used to denote the presence of CMHPs.

Results.

The prevalence of CMHPs was 34.4% in Chinese migrant workers. In multiple logistic regression, risk factors for CMHPs included being 16–25 years old (odd ratio [OR] 1.65, 95% confidence interval [CI] 1.28, 2.12), being 26–35 years old (OR 1.36, 95% CI: 1.05, 1.75), low monthly income (OR 1.42, 95% CI 1.04, 1.92), poor living condition (OR: 1.76, 95% CI: 1.22, 2.54), physical illness in the past 2 weeks (OR 1.72, 95% CI 1.43, 2.05), having worked in many cities (OR 1.34, 95% CI 1.03, 1.74), infrequently visiting hometown (OR 1.56, 95% CI 1.22, 1.99), poor Mandarin proficiency (OR 1.51, 95%CI 1.13, 2.01), a low level of perceived benefits of migration (OR 1.33, 95% CI 1.14, 1.55) and working more than 8 h/day (OR 1.39, 95% CI 1.14, 1.70).

Conclusions.

CMHPs are very prevalent among Chinese migrant workers. Given the large number of Chinese migrant workers, there is an urgent need to address the mental health burden of China's migrant worker population.
The Ecology of Social Learning in Animals and its Link with Intelligence
Authors: van Schaik Carel , Graber Sereina , Schuppli Caroline , Burkart Judith
Published: January 2017

Classical ethology and behavioral ecology did not pay much attention to learning. However, studies of social learning in nature reviewed here reveal the near-ubiquity of reliance on social information for skill acquisition by developing birds and mammals. This conclusion strengthens the plausibility of the cultural intelligence hypothesis for the evolution of intelligence, which assumes that selection on social learning abilities automatically improves individual learning ability. Thus, intelligent species will generally be cultural species. Direct tests of the cultural intelligence hypothesis require good estimates of the amount and kind of social learning taking place in nature in a broad variety of species. These estimates are lacking so far. Here, we start the process of developing a functional classification of social learning, in the form of the social learning spectrum, which should help to predict the mechanisms of social learning involved. Once validated, the categories can be used to estimate the cognitive demands of social learning in the wild.
Cognition and Culture in Evolutionary Context
Authors: Colmenares Fernando , Hernández-Lloreda María Victoria
Published: January 2017

In humans and other animals, the individuals’ ability to adapt efficiently and effectively to the niches they have actively contributed to construct relies heavily on an evolved psychology which has been shaped by biological, social, and cultural processes over evolutionary time. As expected, although many of the behavioral and cognitive components of this evolved psychology are widely shared across species, many others are species-unique. Although many animal species are known to acquire group-specific traditions (or cultures) via social learning, human culture is unique in terms of its contents and characteristics (observable and unobservable products, cumulative effects, norm conformity, and norm enforcement) and of its cognitive underpinnings (imitation, instructed teaching, and language). Here we provide a brief overview of some of the issues that are currently tackled in the field. We also highlight some of the strengths of a biological, comparative, non-anthropocentric and evolutionarily grounded approach to the study of culture. The main contributions of this approach to the science of culture are its emphasis (a) on the integration of information on mechanisms, function, and evolution, and on mechanistic factors located at different levels of the biological hierarchy, and (b) on the search for general principles that account for commonalities and differences between species, both in the cultural products and in the processes of innovation, dissemination, and accumulation involved that operate during developmental and evolutionary timespans.
Germline BRCA2 mutations drive prostate cancers with distinct evolutionary trajectories
Authors: Taylor Renea A. , Fraser Michael , Livingstone Julie , Espiritu Shadrielle Melijah G. , Thorne Heather , Huang Vincent , Lo Winnie , Shiah Yu-Jia , Yamaguchi Takafumi N. , Sliwinski Ania , Horsburgh Sheri , Meng Alice , Heisler Lawrence E. , Yu Nancy , Yousif Fouad , Papargiris Melissa , Lawrence Mitchell G. , Timms Lee , Murphy Declan G. , Frydenberg Mark , Hopkins Julia F. , Bolton Damien , Clouston David , McPherson John D. , van der Kwast Theodorus , Boutros Paul C. , Risbridger Gail P. , Bristow Robert G.
Published: January 2017

Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.
Quantum-chemical insights from deep tensor neural networks
Authors: Schütt Kristof T. , Arbabzadah Farhad , Chmiela Stefan , Müller Klaus R. , Tkatchenko Alexandre
Published: January 2017

Learning from data has led to paradigm shifts in a multitude of disciplines, including web, text and image search, speech recognition, as well as bioinformatics. Can machine learning enable similar breakthroughs in understanding quantum many-body systems? Here we develop an efficient deep learning approach that enables spatially and chemically resolved insights into quantum-mechanical observables of molecular systems. We unify concepts from many-body Hamiltonians with purpose-designed deep tensor neural networks, which leads to size-extensive and uniformly accurate (1 kcal mol−1) predictions in compositional and configurational chemical space for molecules of intermediate size. As an example of chemical relevance, the model reveals a classification of aromatic rings with respect to their stability. Further applications of our model for predicting atomic energies and local chemical potentials in molecules, reliable isomer energies, and molecules with peculiar electronic structure demonstrate the potential of machine learning for revealing insights into complex quantum-chemical systems.
Characterization of the interplay between DNA repair and CRISPR/Cas9-induced DNA lesions at an endogenous locus
Authors: Bothmer Anne , Phadke Tanushree , Barrera Luis A. , Margulies Carrie M , Lee Christina S. , Buquicchio Frank , Moss Sean , Abdulkerim Hayat S. , Selleck William , Jayaram Hariharan , Myer Vic E. , Cotta-Ramusino Cecilia
Published: January 2017

The CRISPR–Cas9 system provides a versatile toolkit for genome engineering that can introduce various DNA lesions at specific genomic locations. However, a better understanding of the nature of these lesions and the repair pathways engaged is critical to realizing the full potential of this technology. Here we characterize the different lesions arising from each Cas9 variant and the resulting repair pathway engagement. We demonstrate that the presence and polarity of the overhang structure is a critical determinant of double-strand break repair pathway choice. Similarly, single nicks deriving from different Cas9 variants differentially activate repair: D10A but not N863A-induced nicks are repaired by homologous recombination. Finally, we demonstrate that homologous recombination is required for repairing lesions using double-stranded, but not single-stranded DNA as a template. This detailed characterization of repair pathway choice in response to CRISPR–Cas9 enables a more deterministic approach for designing research and therapeutic genome engineering strategies.
Ultrafast evolution and transient phases of a prototype out-of-equilibrium Mott–Hubbard material
Authors: Lantz G. , Mansart B. , Grieger D. , Boschetto D. , Nilforoushan N. , Papalazarou E. , Moisan N. , Perfetti L. , Jacques V. L. R. , Le Bolloc'h D. , Laulhé C. , Ravy S. , Rueff J-P , Glover T. E. , Hertlein M. P. , Hussain Z. , Song S. , Chollet M. , Fabrizio M. , Marsi M.
Published: January 2017

The study of photoexcited strongly correlated materials is attracting growing interest since their rich phase diagram often translates into an equally rich out-of-equilibrium behaviour. With femtosecond optical pulses, electronic and lattice degrees of freedom can be transiently decoupled, giving the opportunity of stabilizing new states inaccessible by quasi-adiabatic pathways. Here we show that the prototype Mott–Hubbard material V2O3 presents a transient non-thermal phase developing immediately after ultrafast photoexcitation and lasting few picoseconds. For both the insulating and the metallic phase, the formation of the transient configuration is triggered by the excitation of electrons into the bonding a1g orbital, and is then stabilized by a lattice distortion characterized by a hardening of the A1g coherent phonon, in stark contrast with the softening observed upon heating. Our results show the importance of selective electron–lattice interplay for the ultrafast control of material parameters, and are relevant for the optical manipulation of strongly correlated systems.
Coherent ultra-violet to near-infrared generation in silica ridge waveguides
Authors: Yoon Oh Dong , Yang Ki Youl , Fredrick Connor , Ycas Gabriel , Diddams Scott A. , Vahala Kerry J.
Published: January 2017

Short duration, intense pulses of light can experience dramatic spectral broadening when propagating through lengths of optical fibre. This continuum generation process is caused by a combination of nonlinear optical effects including the formation of dispersive waves. Optical analogues of Cherenkov radiation, these waves allow a pulse to radiate power into a distant spectral region. In this work, efficient and coherent dispersive wave generation of visible to ultraviolet light is demonstrated in silica waveguides on a silicon chip. Unlike fibre broadeners, the arrays provide a wide range of emission wavelength choices on a single, compact chip. This new capability is used to simplify offset frequency measurements of a mode-locked frequency comb. The arrays can also enable mode-locked lasers to attain unprecedented tunable spectral reach for spectroscopy, bioimaging, tomography and metrology.
Multiple Dirac cones at the surface of the topological metal LaBi
Authors: Nayak Jayita , Wu Shu-Chun , Kumar Nitesh , Shekhar Chandra , Singh Sanjay , Fink Jörg , Rienks Emile E. D. , Fecher Gerhard H. , Parkin Stuart S. P. , Yan Binghai , Felser Claudia
Published: January 2017

The rare-earth monopnictide LaBi exhibits exotic magneto-transport properties, including an extremely large and anisotropic magnetoresistance. Experimental evidence for topological surface states is still missing although band inversions have been postulated to induce a topological phase in LaBi. In this work, we have revealed the existence of surface states of LaBi through the observation of three Dirac cones: two coexist at the corners and one appears at the centre of the Brillouin zone, by employing angle-resolved photoemission spectroscopy in conjunction with ab initio calculations. The odd number of surface Dirac cones is a direct consequence of the odd number of band inversions in the bulk band structure, thereby proving that LaBi is a topological, compensated semimetal, which is equivalent to a time-reversal invariant topological insulator. Our findings provide insight into the topological surface states of LaBi’s semi-metallicity and related magneto-transport properties.
Adsorbate-induced lattice deformation in IRMOF-74 series
Authors: Jawahery Sudi , Simon Cory M. , Braun Efrem , Witman Matthew , Tiana Davide , Vlaisavljevich Bess , Smit Berend
Published: January 2017

IRMOF-74 analogues are among the most widely studied metal-organic frameworks (MOFs) for adsorption applications because of their one-dimensional channels and high metal density. Most studies involving the IRMOF-74 series assume that the crystal lattice is rigid. This assumption guides the interpretation of experimental data, as changes in the crystal symmetry have so far been ignored as a possibility in the literature. Here, we report a deformation pattern, induced by the adsorption of argon, for IRMOF-74-V. This work has two main implications. First, we use molecular simulations to demonstrate that the IRMOF-74 series undergoes a deformation that is similar to the mechanism behind breathing MOFs, but is unique because the deformation pattern extends beyond a single unit cell of the original structure. Second, we provide an alternative interpretation of experimental small-angle X-ray scattering profiles of these systems, which changes how we view the fundamentals of adsorption in this MOF series.
Praja1 E3 ubiquitin ligase promotes skeletal myogenesis through degradation of EZH2 upon p38α activation
Authors: Consalvi Silvia , Brancaccio Arianna , Dall’Agnese Alessandra , Puri Pier Lorenzo , Palacios Daniela
Published: January 2017

Polycomb proteins are critical chromatin modifiers that regulate stem cell differentiation via transcriptional repression. In skeletal muscle progenitors Enhancer of zeste homologue 2 (EZH2), the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), contributes to maintain the chromatin of muscle genes in a repressive conformation, whereas its down-regulation allows the progression through the myogenic programme. Here, we show that p38α kinase promotes EZH2 degradation in differentiating muscle cells through phosphorylation of threonine 372. Biochemical and genetic evidence demonstrates that the MYOD-induced E3 ubiquitin ligase Praja1 (PJA1) is involved in regulating EZH2 levels upon p38α activation. EZH2 premature degradation in proliferating myoblasts is prevented by low levels of PJA1, its cytoplasmic localization and the lower activity towards unphosphorylated EZH2. Our results indicate that signal-dependent degradation of EZH2 is a prerequisite for satellite cells differentiation and identify PJA1 as a new player in the epigenetic control of muscle gene expression.
Regional adaptation defines sensitivity to future ocean acidification
Authors: Calosi Piero , Melatunan Sedercor , Turner Lucy M. , Artioli Yuri , Davidson Robert L. , Byrne Jonathan J. , Viant Mark R. , Widdicombe Stephen , Rundle Simon D.
Published: January 2017

Physiological responses to temperature are known to be a major determinant of species distributions and can dictate the sensitivity of populations to global warming. In contrast, little is known about how other major global change drivers, such as ocean acidification (OA), will shape species distributions in the future. Here, by integrating population genetics with experimental data for growth and mineralization, physiology and metabolomics, we demonstrate that the sensitivity of populations of the gastropod Littorina littorea to future OA is shaped by regional adaptation. Individuals from populations towards the edges of the natural latitudinal range in the Northeast Atlantic exhibit greater shell dissolution and the inability to upregulate their metabolism when exposed to low pH, thus appearing most sensitive to low seawater pH. Our results suggest that future levels of OA could mediate temperature-driven shifts in species distributions, thereby influencing future biogeography and the functioning of marine ecosystems.
Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23
Authors: Wei Yao , Wang Dong , Jin Fangfang , Bian Zhen , Li Limin , Liang Hongwei , Li Mingzhen , Shi Lei , Pan Chaoyun , Zhu Dihan , Chen Xi , Hu Gang , Liu Yuan , Zhang Chen-Yu , Zen Ke
Published: January 2017

Tumour cells secrete exosomes that are involved in the remodelling of the tumour–stromal environment and promoting malignancy. The mechanisms governing tumour exosome release, however, remain incompletely understood. Here we show that tumour cell exosomes secretion is controlled by pyruvate kinase type M2 (PKM2), which is upregulated and phosphorylated in tumours. During exosome secretion, phosphorylated PKM2 serves as a protein kinase to phosphorylate synaptosome-associated protein 23 (SNAP-23), which in turn enables the formation of the SNARE complex to allow exosomes release. Direct phosphorylation assay and mass spectrometry confirm that PKM2 phosphorylates SNAP-23 at Ser95. Ectopic expression of non-phosphorylated SNAP-23 mutant (Ser95→Ala95) significantly reduces PKM2-mediated exosomes release whereas expression of selective phosphomimetic SNAP-23 mutants (Ser95→Glu95 but not Ser20→Glu20) rescues the impaired exosomes release induced by PKM2 knockdown. Our findings reveal a non-metabolic function of PKM2, an enzyme associated with tumour cell reliance on aerobic glycolysis, in promoting tumour cell exosome release.
Oxidized nucleotide insertion by pol β confounds ligation during base excision repair
Authors: Çağlayan Melike , Horton Julie K. , Dai Da-Peng , Stefanick Donna F. , Wilson Samuel H.
Published: January 2017

Oxidative stress in cells can lead to accumulation of reactive oxygen species and oxidation of DNA precursors. Oxidized purine nucleotides can be inserted into DNA during replication and repair. The main pathway for correcting oxidized bases in DNA is base excision repair (BER), and in vertebrates DNA polymerase β (pol β) provides gap filling and tailoring functions. Here we report that the DNA ligation step of BER is compromised after pol β insertion of oxidized purine nucleotides into the BER intermediate in vitro. These results suggest the possibility that BER mediated toxic strand breaks are produced in cells under oxidative stress conditions. We observe enhanced cytotoxicity in oxidizing-agent treated pol β expressing mouse fibroblasts, suggesting formation of DNA strand breaks under these treatment conditions. Increased cytotoxicity following MTH1 knockout or treatment with MTH1 inhibitor suggests the oxidation of precursor nucleotides.
Mutant U2AF1-expressing cells are sensitive to pharmacological modulation of the spliceosome
Authors: Shirai Cara Lunn , White Brian S. , Tripathi Manorama , Tapia Roberto , Ley James N. , Ndonwi Matthew , Kim Sanghyun , Shao Jin , Carver Alexa , Saez Borja , Fulton Robert S. , Fronick Catrina , O’Laughlin Michelle , Lagisetti Chandraiah , Webb Thomas R. , Graubert Timothy A. , Walter Matthew J.
Published: January 2017

Somatic mutations in spliceosome genes are detectable in ∼50% of patients with myelodysplastic syndromes (MDS). We hypothesize that cells harbouring spliceosome gene mutations have increased sensitivity to pharmacological perturbation of the spliceosome. We focus on mutant U2AF1 and utilize sudemycin compounds that modulate pre-mRNA splicing. We find that haematopoietic cells expressing mutant U2AF1(S34F), including primary patient cells, have an increased sensitivity toin vitrosudemycin treatment relative to controls.In vivosudemycin treatment of U2AF1(S34F) transgenic mice alters splicing and reverts haematopoietic progenitor cell expansion induced by mutant U2AF1 expression. The splicing effects of sudemycin and U2AF1(S34F) can be cumulative in cells exposed to both perturbations—drug and mutation—compared with cells exposed to either alone. These cumulative effects may result in downstream phenotypic consequences in sudemycin-treated mutant cells. Taken together, these data suggest a potential for treating haematological cancers harbouringU2AF1mutations with pre-mRNA splicing modulators like sudemycins.
Validity of visceral adiposity estimates from DXA against MRI in Kuwaiti men and women
Authors: Mohammad A , De Lucia Rolfe E , Sleigh A , Kivisild T , Behbehani K , Wareham N J , Brage S , Mohammad T
Published: January 2017

Objectives:

The prevalence of obesity and diabetes in the Middle East is among the highest in the world. Valid measures of abdominal adiposity are essential to understanding the metabolic consequences of obesity. Dual-energy X-ray absorptiometry (DXA) is increasingly being utilised to assess body composition in population studies, and has recently been used to estimate visceral adipose tissue (VAT). The aim of this study was to determine the accuracy of DXA-derived VAT in a Middle Eastern population using magnetic resonance imaging (MRI) as the criterion measure.

Method:

VAT was estimated from abdominal DXA measures in 237 adult men (n=130) and women (n=107), aged 18–65 years, participating in the Kuwait Wellbeing Study. These estimates were compared with MRI measures of the corresponding anatomical region. The agreement between methods was assessed using Bland–Altman as well as correlation analysis.

Results:

Median MRI VAT was 1148.5 cm3 (95% confidence interval: 594.2–1734.6) in men and 711.3 cm3 (95% confidence interval: 395.5–1042.8) in women. DXA estimates of VAT showed high correlations with corresponding MRI measures (r=0.94 (P<0.0001) in men; r=0.93 (P<0.0001) in women). DXA overestimated VAT with a mean bias (95% limits of agreement) of 79.7 cm3 (−767 to 963) in men and 46.8 cm3 (−482 to 866) in women. The imprecision of DXA increased with increasing VAT level in both men and women.

Conclusion:

DXA estimates of VAT are valid for use in Middle Eastern populations, although accuracy decreases with increasing level of visceral adiposity.
Impact of type 1 diabetes mellitus and celiac disease on nutrition and quality of life
Authors: Nunes-Silva J G , Nunes V S , Schwartz R P , MLSS Trecco S , Evazian D , Correa-Giannella M L , Nery M , Queiroz M S
Published: January 2017

Objective:

Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are autoimmune diseases and have similar genetic patterns. T1DM treatment is based on diet, physical activity and insulin therapy, whereas CD depends on dietary changes with restriction of wheat, rye and barley. The aim of the study was to evaluate the quality of life (QoL) of individuals with the association of T1DM and CD, to characterize their nutritional status and to compare it with those with only one disease and healthier controls.

Subjects/Methods:

Sixty patients controlled by sex, age and body mass index (BMI) were stratified by previous diagnosis in: T1DM and CD (DMCD group); T1DM (DM group); CD (CD group); or healthy participants (HC). The SF-36 questionnaire was applied to assess psychological well being and results were compared with glycemic control and presence of complications related to diabetes, adhesion to gluten-free diet (GFD). Nutritional status and body mass composition were determined by BMI, waist circumference, bioimpedance, general laboratory tests and whole-body densitometry.

Results:

The time of diagnosis of T1DM was similar between DMCD and DM groups; however, the duration of CD was significantly higher in the CD group compared with DMCD. The SF-36 analysis revealed statistically significant differences between DM and HC groups in two domains: general health (P=0.042) and energy/vitality (P=0.012). QoL was also correlated with compliance to a GFD, and scores were similar in both groups: DMCD and CD. Forty percent of individuals in the CD group had visceral fat area above 100 cm2, as opposed to 20% in the other groups.

Conclusions:

Individuals of DMCD group had similar scores to DM, CD and HC on QoL, as well as on their nutritional status and bone metabolism. Thereby, we should conclude that the association of T1DM and CD did not deteriorate their health status.
Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer
Authors: Xiang J , Fu X , Ran W , Wang Z
Published: January 2017

Metastasis is one of the typical features of malignancy that significantly increases cancer-related mortality. Recent studies have shown that epithelial–mesenchymal transition (EMT) is closely related to the invasion and migration of cancer cells. Grainyhead-like 2 (Grhl2), a transcription factor, has been reported to be associated with several tumor processes including EMT. In the previous study, we have reported that Grhl2 functioned as a tumor suppressor in proliferation and apoptosis of gastric cancer. Here we aim to explore the effects of Grhl2 on invasion and migration of gastric cancer and further clarify its possible underlying mechanisms. As a result, in both SGC7901 and MKN45 cells, Grhl2 overexpression significantly inhibited the ability of invasion and migration. In addition, preliminary experiments showed that Grhl2 reduces the protein expression of matrix metalloproteinase-2, -7 and -9 (MMP-2, MMP-7 and MMP-9). Most importantly, Grhl2 antagonizes transforming growth factor-β (TGFβ)-induced EMT, and inhibition of TGFβ signaling pathways can restore Grhl2 expression. Finally, the results of subcutaneous xenograft model indicated that Grhl2 suppresses the growth of gastric cancer and reverses EMT process in vivo. Meanwhile, the metastatic tumor model further confirmed the inhibition of Grhl2 on metastasis of gastric cancer. Taken together, our findings proved that Grhl2, functioned as a tumor suppressor, reduces the invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer.