bluuebunny/crossref_metadata_2025 huggingface dataset:
Crown sealing and buckling instability during water entry of spheres
Authors: Marston J. O. , Truscott T. T. , Speirs N. B. , Mansoor M. M. , Thoroddsen S. T.
Published: April 2016

We present new observations from an experimental investigation of the classical problem of the crown splash and sealing phenomena observed during the impact of spheres onto quiescent liquid pools. In the experiments, a 6 m tall vacuum chamber was used to provide the required ambient conditions from atmospheric pressure down to $1/16\text{th}$ of an atmosphere, whilst high-speed videography was exploited to focus primarily on the above-surface crown formation and ensuing dynamics, paying particular attention to the moments just prior to the surface seal. In doing so, we have observed a buckling-type azimuthal instability of the crown. This instability is characterised by vertical striations along the crown, between which thin films form that are more susceptible to the air flow and thus are drawn into the closing cavity, where they atomize to form a fine spray within the cavity. To elucidate to the primary mechanisms and forces at play, we varied the sphere diameter, liquid properties and ambient pressure. Furthermore, a comparison between the entry of room-temperature spheres, where the contact line pins around the equator, and Leidenfrost spheres (i.e. an immersed superheated sphere encompassed by a vapour layer), where there is no contact line, indicates that the buckling instability appears in all crown sealing events, but is intensified by the presence of a pinned contact line.
Anchors and snorkels: heterochrony, development and form in functionally constrained fossil crassatellid bivalves
Authors: Collins Katie S. , Crampton James S. , Neil Helen L. , Smith Euan G. C. , Gazley Michael F. , Hannah Michael
Published: April 2016

New growth rate estimates for nine species from three genera of New Zealand Crassatellidae (Mollusca: Bivalvia), combined with existing morphometric ontogenetic descriptions, allow identification of heterochronic processes in the evolution of these genera. Both paedomorphosis (progenesis and neoteny) and peramorphosis (hypermorphosis and acceleration) have occurred within the clade. Overall, morphological variability and response to environmental pressure in this nonsiphonate group is restricted by the interplay of anatomical and life habit constraints. Stability in the substrate, predator avoidance, sluggish burrowing speed, and inability to escape by deep burial are suggested as key drivers of, or constraints on, morphological change. Two groups of shell characters are identified: heavy, armored “anchors” and elongate “snorkels,” which combine juvenile and adult traits in shells of different sizes and ages, produced by heterochronic variation in developmental timing. Anchors and snorkels both represent different “solutions” to the problems of life as a nonsiphonate, infaunal bivalve.
Distribution of energy intake throughout the day and weight gain: a population-based cohort study in Spain
Authors: Hermengildo Ygor , López-García Esther , García-Esquinas Esther , Pérez-Tasigchana Raúl F. , Rodríguez-Artalejo Fernando , Guallar-Castillón Pilar
Published: April 2016

Experimental research suggests that food timing is associated with weight regulation. However, the association between the distribution of energy intake (EI) throughout the day and weight gain in the population is uncertain. A cohort of 4243 individuals (49·9 % men, 50·1 % women) aged ≥18 years was selected in 2008–2010 and followed-up through 2012. At baseline, food consumption for a typical week in the previous year was collected with a validated dietary history, and EI was assessed at six eating occasions: breakfast, mid-morning meal, lunch, mid-afternoon meal, dinner and snacking (at any other moment). Individuals were classified into sex-specific quartiles of %EI for each eating occasion. The cut-off points for increasing quartiles of %EI at lunch were 34·4, 40·8 and 47·7 % in men and 33·2, 39·4 and 46·1 % in women. Weight was self-reported at baseline and at the end of follow-up. During a 3·5-year follow-up, 16·3 % of study participants gained >3 kg. Compared with those in the lowest quartile of %EI at lunch, the multivariate OR of gaining >3 kg was 0·79 (95 % CI 0·63, 0·99) in the second quartile, 0·82 (95 % CI 0·64, 1·04) in the third quartile and 0·62 (95 % CI 0·47, 0·80) in the highest quartile (Ptrend: 0·001). The association was stronger among women and those with overweight or obesity. No association was found between the %EI at the rest of the eating occasions and weight gain. In conclusion, a higher %EI at lunch was associated with a lower risk of weight gain; this may help weight control through the appropriate distribution of daily EI.
Long-term feeding of Atlantic salmon in seawater with low dietary long-chain n-3 fatty acids affects tissue status of the brain, retina and erythrocytes
Authors: Sissener N. H. , Torstensen B. E. , Stubhaug I. , Rosenlund G.
Published: April 2016

In two long-term feeding trials in seawater, Atlantic salmon were fed EPA+DHA in graded levels, from 1·3 to 7·4 % of fatty acids (FA, 4–24 g/kg feed) combined with approximately 10 % 18 : 3n-3, at 6 and 12°C. Dietary EPA appeared to be sufficient in all diet groups, as no differences were seen in polar lipid tissue concentrations of either the brain, retina or erythrocytes. For DHA, a reduction in tissue levels was observed with low dietary supply. Effects on brain DHA at ≤1·4 % EPA+DHA of dietary FA and retina DHA at ≤2·7 % EPA+DHA of dietary FA were only observed in fish reared at 6°C, suggesting an effect of temperature, whereas tissue levels of n-6 FA increased as a response to increased dietary n-6 FA in both the brain and the retina at both temperatures. DHA levels in erythrocytes were affected by ≤2·7 % EPA+DHA at both temperatures. Therefore, DHA appears to be the limiting n-3 FA in diets where EPA and DHA are present in the ratios found in fishmeal and fish oil. To assess the physiological significance of FA differences in erythrocytes, the osmotic resistance was tested, but it did not vary between dietary groups. In conclusion, ≤2·7 % EPA+DHA of FA (≤9 g/kg feed) is not sufficient to maintain tissue DHA status in important tissues of Atlantic salmon throughout the seawater production cycle despite the presence of dietary 18 : 3n-3, and effects may be more severe at low water temperatures.
Indices for the assessment of nutritional quality of meals: a systematic review
Authors: Gorgulho B. M. , Pot G. K. , Sarti F. M. , Marchioni D. M.
Published: April 2016

This systematic review aimed to synthesise information on indices developed to evaluate nutritional quality of meals. A strategy for systematic search of the literature was developed using keywords related to assessment of meal quality. Databases searched included ScienceDirect, PubMed, Lilacs, SciELO, Scopus, Cochrane, Embase and Google Scholar. The literature search resulted in seven different meal quality indices. Each article was analysed in order to identify the following items: authors, country, year, study design, population characteristics, type of meal evaluated, dietary assessment method, characteristics evaluated (nutrients or food items), score range, index components, nutritional references, correlations performed, validation and relationship with an outcome (if existing). Two studies developed instruments to assess the quality of breakfast, three analysed lunch, one evaluated dinner and one was applied to all types of meals and snacks. All meal quality indices reviewed were based on the evaluation of presence or absence of food groups and relative contributions of nutrients, according to food-based guidelines or nutrient references, adapting the daily dietary recommendations to one specific meal. Most of the indices included three items as components for meal quality assessment: (I) total fat or some specific type of fat, (II) fruits and vegetables and (III) cereals or whole grains. This systematic review indicates aspects that need further research, particularly the numerous approaches to assessing meals considering different foods and nutrients, and the need for validation studies of meal indices.
Short- and long-term metabolic responses to diets with different protein:carbohydrate ratios in Senegalese sole (Solea senegalensis, Kaup 1858)
Authors: Conde-Sieira Marta , Salas-Leiton Emilio , Duarte Marta M. , Pelusio Nicole F. , Soengas José L. , Valente Luísa M. P.
Published: April 2016

Four isolipidic and isoenergetic diets with different protein:carbohydrate (CH) contents (48:38, 52:34, 56:30, 60:26) were fed to juvenile Senegalese sole (22·01 (sem0·01) g) during 104 d. Oral glucose tolerance tests were performed at the beginning (4 d) and at the end (104 d) of the experiment to assess the effect of the dietary treatment on glucose tolerance. Samples of blood, liver and muscle of all dietary groups were also obtained at the initial and final phases of the trial at different postprandial times (0, 1, 5 and 10 h after feeding) in order to analyse glucose and NEFA in plasma, and metabolites and enzyme activities involved in glycogen metabolism, glycolysis, gluconeogenesis and lipogenesis pathways in liver and muscle. The results obtained in this study suggest a good glucose tolerance in Senegalese sole. This species tolerated important amounts of CH in the diet without showing any deleterious signs in terms of growth or any metabolic disorders. After 104 d of feeding diets with an important amount of CH (48:38 and 52:34), the control of glycaemia was maintained and even postprandial glucose levels in plasma were (in general) lower than at the beginning of the experiment. This reasonable tolerance to glucose is also reflected by an increased use of glucose through glycolysis in liver (indicated by glucokinase activity), and the absence of changes in lipogenic potential in the same tissue (indicated by ATP citrate lyase activity). No clear changes were induced in the muscle by the dietary treatments.
A Patchwork of Participation: Stewardship, Delegation and the Search for Community Representation in Post-Amalgamation Ontario
Authors: Spicer Zachary
Published: April 2016

In the wake of wide-ranging municipal amalgamations Ontario, the provincial government promoted the use of community councils, citizen-led boards that would have input in local matters. Community councils were touted as a way of preserving local identity and policy control. However, more than a decade removed from Ontario's restructuring process, few municipalities have community councils in place. Those that have implemented community councils established them with purely advisory functions. This paper asks why community councils were so inconsistently implemented and introduced with such limited powers. Overall, it is found that community councils were victims of restructuring politics. Blocked by city councillors fearing decentralization would dilute their authority and foster political rivals, constrained through a restrictive legislative framework and pushed aside by city officials fearing they would effectively recreate a two-tier system, community councils were either abandoned or installed with a limited mandate.
THE AGORANOMOI AT COTYORA (XEN. AN. 5.7.21–9): CERASUNTIANS OR CYREANS?
Authors: O'Connor Stephen
Published: April 2016

In the late spring of 400 b.c.e., when the Ten Thousand were encamped outside the city of Cotyora, Xenophon addressed the soldiers gathered in assembly in order to defend himself against accusations that he was planning to lead them on a colonizing expedition to the land of the Phasis river. Having demonstrated that he was not misleading the soldiers (that is, that his true intentions were not to lead them to the Phasis) by proving that he could not hope to deceive them into travelling east, Xenophon then moved on to what he presented as a more serious matter for the assembled mercenaries: the problem of growing indiscipline in the army, and its consequences (both potential and actual). Xenophon illustrated the extent of the problem by describing to the men two incidents in detail.
RATIONALISM AND THE THEATRE IN LUCRETIUS
Authors: Taylor Barnaby
Published: April 2016

Lucretius' primary didactic aim in De Rerum Natura (DRN) is to teach his readers to interpret the world around them in such a way as to avoid the formation of false beliefs. The price of failure is extremely high. Someone who possesses false beliefs is liable to experience fear (of the gods, or of death, or both), and so will not be able to attain the state of tranquillity that, for Epicureans, constitutes the moral end. Equipping readers with sufficient knowledge always to form true beliefs about the phenomena they encounter thus serves no less a purpose than the enabling of their future happiness. This paper is concerned with how Lucretian intertextuality contributes to this primary didactic aim. For reasons to be explained below, I will focus on Lucretian engagement with the texts of Greek and Roman drama. I will show that allusions to drama in DRN, rather than functioning simply as ‘honey on the rim of the cup’, make a direct contribution to Lucretius' ethical project, teaching readers how to respond rationally to the full variety of their cultural experience.
Placing Madagascar's marine turtle populations in a regional context using community-based monitoring
Authors: Humber Frances , Godley Brendan J. , Nicolas Tanguy , Raynaud Olivier , Pichon Florence , Broderick Annette
Published: April 2016

Madagascar is an important foraging ground for marine turtles in the Western Indian Ocean, yet the status of the country's nesting aggregations remains poorly documented. We assess the current status and trend in nesting throughout Madagascar, including data recorded by a community-based monitoring project in the Barren Isles (western Madagascar). We contextualize the findings in comparison with data from Madagascar's closest neighbouring states. Reports indicate that nesting levels have declined at many coastal sites, with no known recordings since 2000 at > 40 nesting sites. We estimate there are a minimum of 1,200 nests per year in Madagascar, with the largest recorded nesting aggregation (< 1,000 nests per year) found on islands off the west and northern coasts. The majority of nesting aggregations, including those recorded by the community-based monitoring project in the Barren Isles, are relatively small, in the order of < 50 nests per year, yet they are potentially important sources of regional genetic diversity. Nesting on many of the islands (e.g. Tromelin, Europa) around Madagascar has increased over the last 20 years, despite the fact that thousands of turtles probably originating from these sites are taken by fishers in the waters of Madagascar annually. We discuss the importance of protecting small nesting populations, and how community-based monitoring could be an important tool for conserving remote and vulnerable populations and building capacity for natural resource management.
Negative covariance between parasite load and body condition in a population of feral horses
Authors: DEBEFFE LUCIE , MCLOUGHLIN PHILIP D. , MEDILL SARAH A. , STEWART KATHRINE , ANDRES DANIEL , SHURY TODD , WAGNER BRENT , JENKINS EMILY , GILLEARD JOHN S. , POISSANT JOCELYN
Published: April 2016

In wild and domestic animals, gastrointestinal parasites can have significant impacts on host development, condition, health, reproduction and longevity. Improving our understanding of the causes and consequences of individual-level variation in parasite load is therefore of prime interest. Here we investigated the relationship between strongyle fecal egg count (FEC) and body condition in a unique, naturalized population of horses that has never been exposed to anthelmintic drugs (Sable Island, Nova Scotia, Canada). We first quantified variation in FEC and condition for 447 individuals according to intrinsic (sex, age, reproductive status, social status) and extrinsic (group size, location, local density) variables. We then quantified the repeatability of measurements obtained over a field season and tested for covariance between FEC and condition. FECs were high relative to other horse populations (mean eggs per gram ± SD = 1543·28 ± 209·94). FECs generally decreased with age, were higher in lactatingvsnon-lactating females, and unexpectedly lower in males in some part of the island. FECs and condition were both spatially structured, with patterns depending on age, sex and reproductive status. FECs and condition were both repeatable. Most notably, FECs and condition were negatively correlated, especially in adult females.
Dengue and chikungunya: modelling the expansion of mosquito-borne viruses into naïve populations
Authors: WEARING HELEN J. , ROBERT MICHAEL A. , CHRISTOFFERSON REBECCA C.
Published: April 2016

With the recent global spread of a number of mosquito-borne viruses, there is an urgent need to understand the factors that contribute to the ability of viruses to expand into naïve populations. Using dengue and chikungunya viruses as case studies, we detail the necessary components of the expansion process: presence of the mosquito vector; introduction of the virus; and suitable conditions for local transmission. For each component we review the existing modelling approaches that have been used to understand recent emergence events or to assess the risk of future expansions. We identify gaps in our knowledge that are related to each of the distinct aspects of the human-mosquito transmission cycle: mosquito ecology; human–mosquito contact; mosquito–virus interactions; and human–virus interactions. Bridging these gaps poses challenges to both modellers and empiricists, but only through further integration of models and data will we improve our ability to better understand, and ultimately control, several infectious diseases that exert a significant burden on human health.
JÖRG WIDMANN'S JAGDQUARTETT
Authors: Armstrong Asher Ian
Published: April 2016

Jörg Widmann's work embraces everything music history – and beyond – has to offer: Lachenmann, Boulez, the poetry of Baudelaire, Rilke's Late Sonnets and the Screaming Pope paintings of Francis Bacon. His transformative re-imagining of traditional forms is seen nowhere better than in the Jagdquartett, the third in a cycle of five quartets that comprise the core of his œuvre. In the interview around which this article is based he discusses the Jagdquartett and its inspirations in detail, and the possibility of his music representing a kind of meta-modernism.
Forward projection model of non-central catadioptric cameras with spherical mirrors
Authors: Goncalves Nuno , Nogueira Ana Catarina , Miguel Andre Lages
Published: April 2016

Non-central catadioptric vision is widely used in robotics and vision but suffers from the lack of an explicit closed-form forward projection model (FPM) that relates a 3D point with its 2D image. The search for the reflection point where the scene ray is projected is extremely slow and unpractical for real-time applications. Almost all methods thus rely on the assumption of a central projection model, even at the cost of an exact projection.

Two recent methods are able to solve this FPM, presenting a quasi-closed form FPM. However, in the special case of spherical mirrors, further enhancements can be made. We compare these two methods for the computation of the FPM and discuss both approaches in terms of practicality and performance. We also derive new expressions for the FPM on spherical mirrors (extremely useful to robotics and graphics) which speed up its computation.
The role of emotion regulation in childhood obesity: implications for prevention and treatment
Authors: Aparicio E. , Canals J. , Arija V. , De Henauw S. , Michels N.
Published: April 2016

Stress and negative emotions pose a major threat to public health, by increasing the risk of obesity. Since the management process for emotions (emotion regulation; ER) is developed in childhood, we present a novel conceptual framework model for the role of ER in the prevention and treatment of childhood obesity. A narrative review of the literature by electronic database search (MEDLINE, Web of Knowledge and Scopus) was conducted of observational and interventional/experimental literature on ER and obesity and the underlying concepts. We also present an overview of ER intervention techniques. Our model indicates that childhood ER is a link between stress and obesity. Stress along with ineffective ER leads to abnormal cortisol patterns, emotional eating, sedentary lifestyle, reduction of physical activity, and sleep problems. Simultaneously, a healthy lifestyle could show benefits on ER and in developing adaptive ER strategies. In the development of obesity and ER, parents also play a role. By contrast, effective ER skills decrease obesity-related unhealthy behaviour and enhance protective factors, which boost health. The literature contains some observational studies of children but very few intervention studies, most of which are pilot or on-going studies. In conclusion, encouraging effective ER could be a useful new approach for combating and treating childhood obesity. Future ER intervention studies are needed to confirm the validity of this model in children.
Challenging Parties and Anti-Fascism in the Name of Democracy: The Fronte dell'Uomo Qualunque and its Impact on Italy's Republic
Authors: CORDUWENER PEPIJN
Published: April 2016

This article studies the political ideology of the Italian political movement Fronte dell'Uomo Qualunque in the light of the problems of party democracy in Italy. The movement existed only for a few years in the aftermath of the Second World War, but the impact of its ideology on post-war Italy was large. The article argues that the party's ideology should be studied beyond the anti-fascist–fascist divide and that it provides a window onto the contestation of party politics in republican Italy. It contextualises the movement in the political transition from fascism to republic and highlights key elements of the Front's ideology. The article then proceeds to demonstrate how the movement distinguished itself from the parties of the Italian resistance and advocated a radical break with the way in which the relationship between the Italian state and citizens had been practiced through subsequent regimes. The way in which the movement aimed to highlight the alleged similarities between the fascist and republican political order, and its own claim to democratic legitimacy, constitute a distinct political tradition which resurfaced in the political crisis of the 1990s.
Targeting Recovery in Persistent Persecutory Delusions: A Proof of Principle Study of a New Translational Psychological Treatment (the Feeling Safe Programme)
Authors: Freeman Daniel , Bradley Jonathan , Waite Felicity , Sheaves Bryony , DeWeever Natalie , Bourke Emilie , McInerney Josephine , Evans Nicole , Černis Emma , Lister Rachel , Garety Philippa , Dunn Graham
Published: April 2016

Background: Many patients do not respond adequately to current pharmacological or psychological treatments for psychosis. Persistent persecutory delusions are common in clinical services, and cause considerable patient distress and impairment. Our aim has been to build a new translational personalized treatment, with the potential for wide use, that leads to high rates of recovery in persistent persecutory delusions. We have been developing, and evaluating individually, brief modular interventions, each targeting a key causal factor identified from our cognitive model. These modules are now combined in “The Feeling Safe Programme”. Aims: To test the feasibility of a new translational modular treatment for persistent persecutory delusions and provide initial efficacy data. Method: 12 patients with persistent persecutory delusions in the context of non-affective psychosis were offered the 6-month Feeling Safe Programme. After assessment, patients chose from a personalized menu of treatment options. Four weekly baseline assessments were carried out, followed by monthly assessments. Recovery in the delusion was defined as conviction falling below 50% (greater doubt than certainty). Results: 11 patients completed the intervention. One patient withdrew before the first monthly assessment due to physical health problems. An average of 20 sessions (SD = 4.4) were received. Posttreatment, 7 out of 11 (64%) patients had recovery in their persistent delusions. Satisfaction ratings were high. Conclusions: The Feeling Safe Programme is feasible to use and was associated with large clinical benefits. To our knowledge this is the first treatment report focused on delusion recovery. The treatment will be tested in a randomized controlled trial.
MONETARY POLICY AND DEBT DEFLATION: SOME COMPUTATIONAL EXPERIMENTS
Authors: Chiarella C. , Di Guilmi C.
Published: April 2016

The paper presents an agent-based model to study the possible effects of different fiscal and monetary policies in the context of debt deflation. We introduce a modified Taylor rule that includes the financial position of firms as a target. Monte Carlo simulations provide a representation of the complex feedback effects generated by the interaction among the different transmission channels of monetary policy. The model also reproduces the evidence of low inflation during stock market booms and shows how it can lead to overinvestment and destabilize the system. The paper also investigates the possible reasons behind this stylized fact by testing different behavioral rules for the central bank. We find that, in a context of sticky prices and volatile expectations, endogenous credit creation can be identified as the main source of the divergent dynamics of prices in the real and financial sectors.
STABILIZATION AND COMMITMENT: FORWARD GUIDANCE IN ECONOMIES WITH RATIONAL EXPECTATIONS
Authors: Hughes Hallett Andrew , Acocella Nicola
Published: April 2016

We construct a theory of forward guidance in economic policy making in order to provide a framework for explaining the role and strategic advantages of including forward guidance as an explicit part of policy design. We do this by setting up a general policy problem in which forward guidance plays a role, and then examine the consequences for performance when that guidance is withdrawn. We show that forward guidance provides enhanced controllability and stabilizability—especially where such properties may not otherwise be available. As a by-product, we find that forward guidance limits the scope and incentives for time-inconsistent behavior in an economy whose policy goals are ultimately reachable. It also adds to the credibility of a set of policies.
AGREEMENT THEOREMS FOR SELF-LOCATING BELIEF
Authors: CAIE MICHAEL
Published: April 2016

In this paper, I first outline Aumann’s famous “no agreeing to disagree” theorem, and a second related theorem. These results show that if two or more agents, who have epistemic and credal states that are defined over algebras that do not include any self-locating propositions, have certain information about one another’s epistemic and credal states, then such agents must assign the same credence to certain propositions. I show, however, that both of these theorems fail when we consider agents who have epistemic and credal states that are defined over algebras that do include self-locating propositions. Importantly, these theorems fail for such agents even when we restrict our attention to the credences that such agents have in non-self-locating propositions. Having established this negative result, I then outline and prove three agreement theorems that hold for such agents.
The biological function of type I receptors of bone morphogenetic protein in bone
Authors: Lin Shuxian , Svoboda Kathy K H , Feng Jian Q , Jiang Xinquan
Published: April 2016

Bone morphogenetic proteins (BMPs) have multiple roles in skeletal development, homeostasis and regeneration. BMPs signal via type I and type II serine/threonine kinase receptors (BMPRI and BMPRII). In recent decades, genetic studies in humans and mice have demonstrated that perturbations in BMP signaling via BMPRI resulted in various diseases in bone, cartilage, and muscles. In this review, we focus on all three types of BMPRI, which consist of activin-like kinase 2 (ALK2, also called type IA activin receptor), activin-like kinase 3 (ALK3, also called BMPRIA), and activin-like kinase 6 (ALK6, also called BMPRIB). The research areas covered include the current progress regarding the roles of these receptors during myogenesis, chondrogenesis, and osteogenesis. Understanding the physiological and pathological functions of these receptors at the cellular and molecular levels will advance drug development and tissue regeneration for treating musculoskeletal diseases and bone defects in the future.
Mitochondrial DNA plasticity is an essential inducer of tumorigenesis
Authors: Lee W T Y , Cain J E , Cuddihy A , Johnson J , Dickinson A , Yeung K-Y , Kumar B , Johns T G , Watkins D N , Spencer A , St John J C
Published: April 2016

Although mitochondrial DNA has been implicated in diseases such as cancer, its role remains to be defined. Using three models of tumorigenesis, namely glioblastoma multiforme, multiple myeloma and osteosarcoma, we show that mitochondrial DNA plays defining roles at early and late tumour progression. Specifically, tumour cells partially or completely depleted of mitochondrial DNA either restored their mitochondrial DNA content or actively recruited mitochondrial DNA, which affected the rate of tumorigenesis. Nevertheless, non-depleted tumour cells modulated mitochondrial DNA copy number at early and late progression in a mitochondrial DNA genotype-specific manner. In glioblastoma multiforme and osteosarcoma, this was coupled with loss and gain of mitochondrial DNA variants. Changes in mitochondrial DNA genotype affected tumour morphology and gene expression patterns at early and late progression. Importantly, this identified a subset of genes that are essential to early progression. Consequently, mitochondrial DNA and commonly expressed early tumour-specific genes provide novel targets against tumorigenesis.
TCR transgenic mice reveal the impact of type 1 diabetes loci on early and late disease checkpoints
Authors: Hillhouse Erin E , Liston Adrian , Collin Roxanne , Desautels Eric , Goodnow Christopher C , Lesage Sylvie
Published: April 2016

Linkage analysis studies for autoimmune diabetes have revealed multiple non‐major histocompatibility complex (MHC) chromosomal regions linked to disease susceptibility. To date, more than 20 insulin‐dependent diabetes (Idd) loci linked to diabetes susceptibility have been identified in NOD mice and validated via congenic breeding. Importantly, evidence suggests that Idd loci may regulate at least two pathological steps during autoimmune diabetes development, namely the onset of insulitis and the transition from insulitis to overt diabetes. Here we assess the role of various non‐MHC Idd diabetes‐resistance loci, which have been validated in the non‐transgenic setting, on autoimmune diabetes progression in the transgenic setting. Specifically, we generated multiple Idd congenic strains in the 3A9‐TCR:insHEL NOD.H2k transgenic model and monitored their diabetes incidence. We show that 3A9‐TCR:insHEL NOD.H2k mice congenic for Idd3 or Idd5 display a reduction in diabetes development, whereas mice congenic for Idd9 or Idd13 exhibit an increase, in comparison with 3A9‐TCR:insHEL NOD.H2k mice. These results suggest that the presence of the 3A9‐TCR and hen egg lysosyme transgenes can offset the regulatory function of certain diabetes‐resistance genetic variants contained within the Idd loci, including Idd9 and Idd13. We propose the antigen‐specific 3A9‐TCR:insHEL transgenic model as a useful tool for the study of the genetics of autoimmune diabetes development.
Genetic diversity affects ecological performance and stress response of marine diatom populations
Authors: Sjöqvist Conny O , Kremp Anke
Published: April 2016

Genetic diversity is considered an important factor, stabilizing ecological functions when organisms are faced with changing environmental conditions. Although well known from terrestrial systems, documentations of this relationship from marine organisms, and particularly planktonic microorganisms, are still limited. Here we experimentally tested the effects of genotypic diversity on ecologically relevant cellular parameters (growth, primary production, particulate organic carbon, particulate organic nitrogen, particulate organic phosphorus and biogenic silica) at optimal and suboptimal salinity conditions in a marine phytoplankton species. Multiple clonal genotyped and phenotypically characterized isolates of the diatom Skeletonema marinoi from the Baltic Sea were grown in monocultures and mixes of 5 and 20 clones at native (5 psu) and reduced (3 psu) salinities and respective parameters were compared. Re-genotyping of 30 individuals from each population at five microsatellite loci at the end of the experiment confirmed maintenance of genotypic richness. Although a diversity effect on growth was not detected, primary production and particulate organic nutrients were positively affected by increased diversity independent of salinity condition. Under salinity stress, highest values of primary production and particulate organic nitrogen content were measured at the high diversity level. The observed diversity effects emphasize the importance of genetic diversity of phytoplankton populations for ecological functions.
Disease dynamics and costly punishment can foster socially imposed monogamy
Authors: Bauch Chris T. , McElreath Richard
Published: April 2016

Socially imposed monogamy in humans is an evolutionary puzzle because it requires costly punishment by those who impose the norm. Moreover, most societies were—and are—polygynous; yet many larger human societies transitioned from polygyny to socially imposed monogamy beginning with the advent of agriculture and larger residential groups. We use a simulation model to explore how interactions between group size, sexually transmitted infection (STI) dynamics and social norms can explain the timing and emergence of socially imposed monogamy. Polygyny dominates when groups are too small to sustain STIs. However, in larger groups, STIs become endemic (especially in concurrent polygynist networks) and have an impact on fertility, thereby mediating multilevel selection. Punishment of polygynists improves monogamist fitness within groups by reducing their STI exposure, and between groups by enabling punishing monogamist groups to outcompete polygynists. This suggests pathways for the emergence of socially imposed monogamy, and enriches our understanding of costly punishment evolution.
Diffractive imaging of a rotational wavepacket in nitrogen molecules with femtosecond megaelectronvolt electron pulses
Authors: Yang Jie , Guehr Markus , Vecchione Theodore , Robinson Matthew S. , Li Renkai , Hartmann Nick , Shen Xiaozhe , Coffee Ryan , Corbett Jeff , Fry Alan , Gaffney Kelly , Gorkhover Tais , Hast Carsten , Jobe Keith , Makasyuk Igor , Reid Alexander , Robinson Joseph , Vetter Sharon , Wang Fenglin , Weathersby Stephen , Yoneda Charles , Centurion Martin , Wang Xijie
Published: April 2016

Imaging changes in molecular geometries on their natural femtosecond timescale with sub-Angström spatial precision is one of the critical challenges in the chemical sciences, as the nuclear geometry changes determine the molecular reactivity. For photoexcited molecules, the nuclear dynamics determine the photoenergy conversion path and efficiency. Here we report a gas-phase electron diffraction experiment using megaelectronvolt (MeV) electrons, where we captured the rotational wavepacket dynamics of nonadiabatically laser-aligned nitrogen molecules. We achieved a combination of 100 fs root-mean-squared temporal resolution and sub-Angstrom (0.76 Å) spatial resolution that makes it possible to resolve the position of the nuclei within the molecule. In addition, the diffraction patterns reveal the angular distribution of the molecules, which changes from prolate (aligned) to oblate (anti-aligned) in 300 fs. Our results demonstrate a significant and promising step towards making atomically resolved movies of molecular reactions.
Parametric excitation and squeezing in a many-body spinor condensate
Authors: Hoang T. M. , Anquez M. , Robbins B. A. , Yang X. Y. , Land B. J. , Hamley C. D. , Chapman M. S.
Published: April 2016

Atomic spins are usually manipulated using radio frequency or microwave fields to excite Rabi oscillations between different spin states. These are single-particle quantum control techniques that perform ideally with individual particles or non-interacting ensembles. In many-body systems, inter-particle interactions are unavoidable; however, interactions can be used to realize new control schemes unique to interacting systems. Here we demonstrate a many-body control scheme to coherently excite and control the quantum spin states of an atomic Bose gas that realizes parametric excitation of many-body collective spin states by time varying the relative strength of the Zeeman and spin-dependent collisional interaction energies at multiples of the natural frequency of the system. Although parametric excitation of a classical system is ineffective from the ground state, we show that in our experiment, parametric excitation from the quantum ground state leads to the generation of quantum squeezed states.
A general strategy for expanding polymerase function by droplet microfluidics
Authors: Larsen Andrew C. , Dunn Matthew R. , Hatch Andrew , Sau Sujay P. , Youngbull Cody , Chaput John C.
Published: April 2016

Polymerases that synthesize artificial genetic polymers hold great promise for advancing future applications in synthetic biology. However, engineering natural polymerases to replicate unnatural genetic polymers is a challenging problem. Here we present droplet-based optical polymerase sorting (DrOPS) as a general strategy for expanding polymerase function that employs an optical sensor to monitor polymerase activity inside the microenvironment of a uniform synthetic compartment generated by microfluidics. We validated this approach by performing a complete cycle of encapsulation, sorting and recovery on a doped library and observed an enrichment of ∼1,200-fold for a model engineered polymerase. We then applied our method to evolve a manganese-independent α-L-threofuranosyl nucleic acid (TNA) polymerase that functions with >99% template-copying fidelity. Based on our findings, we suggest that DrOPS is a versatile tool that could be used to evolve any polymerase function, where optical detection can be achieved by Watson–Crick base pairing.
Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades
Authors: Liu Zhichao , Wang Yuping , Borlak Jürgen , Tong Weida
Published: April 2016

Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades.
BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS
Authors: Huang Mingcheng , Qiu Qian , Xiao Youjun , Zeng Shan , Zhan Mingying , Shi Maohua , Zou Yaoyao , Ye Yujin , Liang Liuqin , Yang Xiuyan , Xu Hanshi
Published: April 2016

The tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a critical modulator of angiogenesis. Increasing evidence indicate the important role of bromodomain and extra-terminal domain (BET) of chromatin adaptors in regulating tumor growth and inflammatory response. However, whether BET proteins have a role in angiogenesis and endothelial permeability is unclear. In this study, we observed that treatment with JQ1, a specific BET inhibitor, suppressed in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis in a Matrigel plug and oxygen-induced retinopathy neovascularization. JQ1 attenuated the VEGF-induced decrease in TEER in HUVECs and prevented Evans blue dye leakage in the VEGF-induced Miles assay in athymic Balb/c nude mice. BET inhibition with JQ1 or shRNA for Brd2 or Brd4 suppressed VEGF-induced migration, proliferation and stress fiber formation of HUVECs. Furthermore, BET inhibition suppressed phosphorylation of VEGFR2 and PAK1, as well as eNOS activation in VEGF-stimulated HUVECs. Inhibition with VEGFR2 and PAK1 also reduced migration and proliferation and attenuated the VEGF-induced decrease in TEER. Thus, our observations suggest the important role of BET bromodomain in regulating VEGF-induced angiogenesis. Strategies that target the BET bromodomain may provide a new therapeutic approach for angiogenesis-related diseases.
LncRNA—UCA1 enhances cell proliferation and 5-fluorouracil resistance in colorectal cancer by inhibiting miR-204-5p
Authors: Bian Zehua , Jin Liugen , Zhang Jiwei , Yin Yuan , Quan Chao , Hu Yaling , Feng Yuyang , Liu Heyong , Fei Bojian , Mao Yong , Zhou Leyuan , Qi Xiaowei , Huang Shenlin , Hua Dong , Xing Chungen , Huang Zhaohui
Published: April 2016

Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p-CREB1/BCL2/RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.
Resilient help to switch and overlap hierarchical subsystems in a small human group
Authors: Fujii K. , Yokoyama K. , Koyama T. , Rikukawa A. , Yamada H. , Yamamoto Y.
Published: April 2016

Groups of social organisms in nature are resilient systems that can overcome unpredicted threats by helping its members. These social organisms are assumed to behave both autonomously and cooperatively as individuals, the helper, the helped and other part of a group depending on the context such as emergencies. However, the structure and function of these resilient actions, such as how helpers help colleagues and how the helper’s action is effective at multiple subsystem scales remain unclear. Here we investigated the behaviour of organised and efficient small human groups in a ballgame defence and identified three principles of hierarchical resilient help when under attack. First, at a present high emergency level, the helper simply switched the local roles in the attacked subsystem with the helped. Second, at an intermediate emergency level, the helpers effectively acted in overlapping subsystems. Third, for the most critical emergency, the helpers globally switched the action on the overall system. These resilient actions to the benefit of the system were assumed to be observed in only humans, which help colleagues at flexibly switched and overlapped hierarchical subsystem. We suggest that these multi-layered helping behaviours can help to understand resilient cooperation in social organisms and human groups.
Controlling superconducting spin flow with spin-flip immunity using a single homogeneous ferromagnet
Authors: Jacobsen Sol H. , Kulagina Iryna , Linder Jacob
Published: April 2016

Spin transport via electrons is typically plagued by Joule heating and short decay lengths due to spin-flip scattering. It is known that dissipationless spin currents can arise when using conventional superconducting contacts, yet this has only been experimentally demonstrated when using intricate magnetically inhomogeneous multilayers, or in extreme cases such as half-metals with interfacial magnetic disorder. Moreover, it is unknown how such spin supercurrents decay in the presence of spin-flip scattering. Here, we present a method for generating a spin supercurrent by using only a single homogeneous magnetic element. Remarkably, the spin supercurrent generated in this way does not decay spatially, in stark contrast to normal spin currents that remain polarized only up to the spin relaxation length. We also expose the existence of a superconductivity-mediated torque even without magnetic inhomogeneities, showing that the different components of the spin supercurrent polarization respond fundamentally differently to a change in the superconducting phase difference. This establishes a mechanism for tuning dissipationless spin and charge flow separately and confirms the advantage that superconductors can offer in spintronics.
MicroRNA profiling of cisplatin-resistant oral squamous cell carcinoma cell lines enriched with cancer-stem-cell-like and epithelial-mesenchymal transition-type features
Authors: Ghosh Ruma Dey , Ghuwalewala Sangeeta , Das Pijush , Mandloi Sapan , Alam Sk Kayum , Chakraborty Jayanta , Sarkar Sajal , Chakrabarti Saikat , Panda Chinmoy Kumar , Roychoudhury Susanta
Published: April 2016

Oral cancer is of major public health problem in India. Current investigation was aimed to identify the specific deregulated miRNAs which are responsible for development of resistance phenotype through regulating their resistance related target gene expression in oral squamous cell carcinoma (OSCC). Cisplatin-resistant OSCC cell lines were developed from their parental human OSCC cell lines and subsequently characterised. The resistant cells exhibited enhanced proliferative, clonogenic capacity with significant up-regulation of P-glycoprotein (ABCB1), c-Myc, survivin, β-catenin and a putative cancer-stem-like signature with increased expression of CD44, whereas the loss of E-cadherin signifies induced EMT phenotype. A comparative analysis of miRNA expression profiling in parental and cisplatin-resistant OSCC cell lines for a selected sets (deregulated miRNAs in head and neck cancer) revealed resistance specific signature. Moreover, we observed similar expression pattern for these resistance specific signature miRNAs in neoadjuvant chemotherapy treated and recurrent tumours compared to those with newly diagnosed primary tumours in patients with OSCC. All these results revealed that these miRNAs play an important role in the development of cisplatin-resistance mainly through modulating cancer stem-cell-like and EMT-type properties in OSCC.