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In plants, transgenerational inheritance of some epialleles has been demonstrated but it remains controversial whether epigenetic variation is subject to selection and contributes to adaptation. Simulating selection in a rapidly changing environment, we compare phenotypic traits and epigenetic variation between Arabidopsis thaliana populations grown for five generations under selection and their genetically nearly identical ancestors. Selected populations of two distinct genotypes show significant differences in flowering time and plant architecture, which are maintained for at least 2–3 generations in the absence of selection. While we cannot detect consistent genetic changes, we observe a reduction of epigenetic diversity and changes in the methylation state of about 50,000 cytosines, some of which are associated with phenotypic changes. Thus, we propose that epigenetic variation is subject to selection and can contribute to rapid adaptive responses, although the extent to which epigenetics plays a role in adaptation is still unclear. Whether plant epigenetic variation is subject to selection and contributes to adaptation is under debate. Here, the authors compare DNA methylation and phenotypes of Arabidopsis lines subject to simulated selection and their nearly isogenic ancestors and provide evidence that epigenetic variation contributes to adaptive responses.

This major new Handbook synthesises more than two decades of scholarly research, and provides a comprehensive overview of the field of terrorism studies. The content of the Handbook is based on the responses to a questionnaire by nearly 100 experts from more than 20 countries as well as the specific expertise and experience of the volume editor and the various contributors. Together, they guide the reader through the voluminous literature on terrorism, and propose a new consensus definition of terrorism, based on an extensive review of existing conceptualisations. The work also features a large collection of typologies and surveys a wide range of theories of terrorism. Additional chapters survey terrorist databases and provide a guide to available resources on terrorism in libraries and on the Internet. It also includes the most comprehensive World Directory of Extremist, Terrorist and other Organizations associated with Guerrilla Warfare, Political Violence, Protest and Organized- and Cyber-Crime. The Routledge Handbook of Terrorism Research will be an essential work of reference for students and researchers of terrorism and political violence, security studies, criminology, political science and international relations, and of great interest to policymakers and professionals in the field of counter-terrorism.

In recent years, linguists have increasingly turned to the cognitive sciences to broaden their investigation into the roots and development of language. With the advent of cognitive-linguistic, usage-based and complex-adaptive models of language, linguists today are utilizing approaches and insights from cognitive psychology, neuropsychology, social psychology and other related fields. A key result of this interdisciplinary approach is the concept of entrenchment —the ongoing reorganization and adaptation of communicative knowledge. Entrenchment posits that our linguistic knowledge is continuously refreshed and reorganized under the influence of social interactions. It is part of a larger, ongoing process of lifelong cognitive reorganization whose course and quality is conditioned by exposure to and use of language, and by the application of cognitive abilities and processes to language. This volume enlists more than two dozen experts in the fields of linguistics, psycholinguistics, neurology, and cognitive psychology in providing a realistic picture of the psychological and linguistic foundations of language. Contributors examine the psychological foundations of linguistic entrenchment processes, and the role of entrenchment in first-language acquisition, second language learning, and language attrition. Critical views of entrenchment and some of its premises and implications are discussed from the perspective of dynamic complexity theory and radical embodied cognitive science.

The description of coherent features of fluid flow is essential to our understanding of fluid-dynamical and transport processes. A method is introduced that is able to extract dynamic information from flow fields that are either generated by a (direct) numerical simulation or visualized/measured in a physical experiment. The extracted dynamic modes, which can be interpreted as a generalization of global stability modes, can be used to describe the underlying physical mechanisms captured in the data sequence or to project large-scale problems onto a dynamical system of significantly fewer degrees of freedom. The concentration on subdomains of the flow field where relevant dynamics is expected allows the dissection of a complex flow into regions of localized instability phenomena and further illustrates the flexibility of the method, as does the description of the dynamics within a spatial framework. Demonstrations of the method are presented consisting of a plane channel flow, flow over a two-dimensional cavity, wake flow behind a flexible membrane and a jet passing between two cylinders.

Searching multiple sources when conducting systematic reviews is considered good practice. We aimed to investigate the impact of using sources beyond PubMed in systematic reviews of therapeutic interventions. We randomly selected 50 Cochrane reviews that searched the PubMed (or MEDLINE) and EMBASE databases and included a meta-analysis of ≥10 studies. We checked whether each eligible record in each review (n = 2,700) was retrievable in PubMed and EMBASE. For the first-listed meta-analysis of ≥10 studies in each review, we examined whether excluding studies not found in PubMed affected results. A median of one record per review was indexed in EMBASE but not in PubMed; a median of four records per review was not indexed in PubMed or EMBASE. Meta-analyses included a median of 13.5 studies; a median of zero studies per meta-analysis was indexed in EMBASE but not in PubMed; a median of one study per meta-analysis was not indexed in PubMed or EMBASE. Meta-analysis using only PubMed-indexed vs. all available studies led to a different conclusion in a single case (on the basis of conventional criteria for statistical significance). In meta-regression analyses, effects in PubMed- vs. non–PubMed-indexed studies were statistically significantly different in a single data set. For systematic reviews of the effects of therapeutic interventions, gains from searching sources beyond PubMed, and from searching EMBASE in particular are modest.

Dengue virus (DENV) causes the most prevalent arthropod-borne viral disease in humans. Although Aedes mosquitoes transmit DENV when probing for blood in the skin, no information exists on DENV infection and immune response in the dermis, where the blood vessels are found. DENV suppresses the interferon response, replicates, and causes disease in humans but not wild-type mice. Here, we used mice lacking the interferon-α/β receptor (Ifnar(-/-)), which had normal cell populations in the skin and were susceptible to intradermal DENV infection, to investigate the dynamics of early DENV infection of immune cells in the skin. CD103(+) classical dendritic cells (cDCs), Ly6C(-) CD11b(+) cDCs, and macrophages in the steady-state dermis were initial targets of DENV infection 12-24 hours post-inoculation but then decreased in frequency. We demonstrated recruitment of adoptively-transferred Ly6C(high) monocytes from wild-type and Ifnar(-/-) origin to the DENV-infected dermis and differentiation to Ly6C(+) CD11b(+) monocyte-derived DCs (moDCs), which became DENV-infected after 48 hours, and were then the major targets for virus replication. Ly6C(high) monocytes that entered the DENV-infected dermis expressed chemokine receptor CCR2, likely mediating recruitment. Further, we show that ∼ 100-fold more hematopoietic cells in the dermis were DENV-infected compared to Langerhans cells in the epidermis. Overall, these results identify the dermis as the main site of early DENV replication and show that DENV infection in the skin occurs in two waves: initial infection of resident cDCs and macrophages, followed by infection of monocytes and moDCs that are recruited to the dermis. Our study reveals a novel viral strategy of exploiting monocyte recruitment to increase the number of targets for infection at the site of invasion in the skin and highlights the skin as a potential site for therapeutic action or intradermal vaccination.

Trisha Greenhalgh and colleagues argue that it is time to apply the precautionary principle

Much has been published about different aspects of body-size distribution resting on the assumptions of metabolic scaling, although a number of studies in aquatic ecosystems have questioned its generality. This study considers the effects of individual body-mass and biomass variability on scaling properties of multi-species communities (protists, meio- and macroinvertebrates), and their intrinsic variations in assemblage structure. We examine how size traits within communities are distributed on local and regional scales and assess the potential sources of variation affecting whole ecosystems. Our results, built upon seven river catchment communities including 1204 species, revealed micro-meiofauna-dominated biomass distributions driven by stochastic hydrophysical processes that induce a fractal fluctuation scaling, irrespective of trophic levels, shaping local and regional scaling relations. Fractal-scaling differences are largely generated by the frequency of high flow events that influence the biomass assemblage configurations, which are significantly better represented by the Power Fraction model compared to single statistical random models. We conclude that environmental random variability contributes to the decoupling of total biomass and body mass per site from assemblage size, resulting in scale-invariant body-size traits among assemblages and systems. Generally, these findings emphasize that ignoring small-sized species and, thus, the wide range of body sizes makes accurate ecological model predictions, impossible.

The generation of discrete acoustic tones in the compressible flow around an aerofoil is addressed in this work by means of nonlinear numerical simulations and global stability analyses. The nonlinear simulations confirm the appearance of discrete tones in the acoustic spectrum and, for the chosen flow case, the global stability analyses of the mean-flow dynamics reveal that the linearized operator is stable. However, the flow response to incoming disturbances exhibits important transient growth effects that culminate in the onset of aeroacoustic feedback loops, involving instability processes on the suction- and pressure-surface boundary layers together with their cross-interaction by acoustic radiation at the trailing edge. The features of the aeroacoustic feedback loops and the appearance of discrete tones are then related to the features of the least-stable modes in the global spectrum: the spatial structure of the direct modes displays the coupled dynamics of hydrodynamic instabilities on the suction surface and in the near wake. Finally, different families of global modes will be identified and the dynamics that they represent will be discussed.

By integrating a 3D nanopositioner with a solid-state nanopore and surface-tethered molecules, precise spatiotemporal control over single DNA strands is achieved, enabling numerous re-reads and raising the signal-to-noise ratio far beyond previous solid-state nanopore methods.