Sonic hedgehog-expressing cells in the developing limb measure time by an intrinsic cell cycle clock

How time is measured is an enduring issue in developmental biology. Classical models of somitogenesis and limb development implicated intrinsic cell cycle clocks, but their existence remains controversial. Here we show that an intrinsic cell cycle clock in polarizing region cells of the chick limb bud times the duration of Sonic hedgehog (Shh) expression, which encodes the morphogen specifying digit pattern across the antero-posterior axis (thumb to little finger). Timing by this clock starts when polarizing region cells fall out of range of retinoic acid signalling. We found that timing of Shh transcription by the cell cycle clock can be reset, thus revealing an embryonic form of self-renewal. In contrast, antero-posterior positional values cannot be reset, suggesting that this may be an important constraint on digit regeneration. Our findings provide the first evidence for an intrinsic cell cycle timer controlling duration and patterning activity of a major embryonic signalling centre

An intrinsic timer specifies distal structures of the vertebrate limb

How the positional values along the proximo-distal axis (stylopod-zeugopod-autopod) of the limb are specified is intensely debated. Early work suggested that cells intrinsically change their proximo-distal positional values by measuring time. Recently, however, it is suggested that instructive extrinsic signals from the trunk and apical ectodermal ridge specify the stylopod and zeugopod/autopod, respectively. Here, we show that the zeugopod and autopod are specified by an intrinsic timing mechanism. By grafting green fluorescent protein-expressing cells from early to late chick wing buds, we demonstrate that distal mesenchyme cells intrinsically time Hoxa13 expression, cell cycle parameters and the duration of the overlying apical ectodermal ridge. In addition, we reveal that cell affinities intrinsically change in the distal mesenchyme, which we suggest results in a gradient of positional values along the proximo-distal axis. We propose a complete model in which a switch from extrinsic signalling to intrinsic timing patterns the vertebrate limb

Study on the gender dimension of trafficking in human beings

The purpose of this study is to contribute to the identification and understanding of what it means to be ‘taking into account the gender perspective, to strengthen the prevention of this crime and protection of the victims there-of’, as required in Article 1 of European Union (EU) Directive 2011/36/EU on Preventing and Combating Trafficking in Human Beings and Protecting its Victims in the context of the EU Strategy (COM(2012) 286 final) Towards the Eradication of Trafficking in Human Beings. The study contributes to Priority E Action 2 of the Strategy, which states that ‘the Commission will develop knowledge on the gender dimensions of human trafficking, including the gender consequences of the various forms of trafficking and potential differences in the vulnerability of men and women to victimisation and its impact on them.’ Its specific objectives and tasks are to address: the ‘gender dimension of vulnerability, recruitment, and victimisation’; ‘gender issues related to traffickers and to those creating demand’; and ‘an examination of law and policy responses on trafficking in human beings from a gender perspective’. The study addresses the five priorities of the EU Strategy: identifying, protecting, and assisting victims of traf-ficking; stepping up the prevention of trafficking in human beings; better law enforcement; enhanced coordination and cooperation among key actors and policy coherence; and increased knowledge of an effective response to emerging concerns. This study, according to its terms of reference, aims to look specifically at the gender dimension of trafficking for the purpose of sexual exploitation. This follows evidence from statistical data from Eurostat, as well as da-ta from The European Police Office (Europol) and the United Nations Office on Drugs and Crime (UNODC), accord-ing to which the most reported form of exploitation of victims is that of sexual exploitation and its strong gen-der dimension (96 % women and girls). It further addresses recommendations addressed in the Resolution of the European Parliament of 26 February 2014 on sexual exploitation and prostitution and its impact on gender equality (2013/2103(INI)) urging the European Commission to evaluate the impact that the European legal frame-work designed to eliminate trafficking for sexual exploitation has had to date and to undertake further research on patterns of prostitution, on human trafficking for the purpose of sexual exploitation and on the increased lev-el of sex tourism in the EU, with particular reference to minors, and to promote the exchange of best practices among the Member States. The study identifies and draws on EU law and policy competence in gender equality in its identification of the gen-der dimensions of trafficking. The gender dimensions are clustered into five issues: gender specificity and equal treatment; gender expertise, gender balance in decision-making and gender mainstreaming; the relationship be-tween prostitution and trafficking; gendered policy fields and strategic priorities; gendered systems and the the-ory of prevention

New insights into seasonal foraging ranges and migrations of minke whales from the Salish Sea and coastal British Columbia.

In the Salish Sea and coastal waters of British Columbia, minke whales are known to establish small home ranges during the feeding season. Beyond the feeding season little is known of their movements or distribution. To determine movement patterns of minke whales in these waters we used photo-identification data that were collected opportunistically from 2005-2012. These data were from four non-overlapping areas between 48ºN and 53ºN. Despite year-round search effort, minke whales were only encountered between April and October. Most of the 44 unique minke whales identified in 405 encounters displayed fidelity to areas both within and among feeding seasons. Five of these individuals also made relatively large-scale intra-annual movements between areas on six occasions. They were documented to move up to at least 424km in a northerly direction early in the season and up to at least 398km in a southerly direction late in the season. We believe that the seasonal patterns of these movements provide new insight into the foraging ranges and migrations of individuals. Ecological markers provide further evidence that the minke whales we photographed undertake annual long distance migrations. Scars believed to be from cookiecutter shark bites were observed on 43 individuals and the majority of minke whales documented with good quality images each year had acquired new scars since the previous feeding season. Furthermore, the commensal barnacle Xenobalanus globicipitis was observed on three individuals. Since these sharks and barnacles are from warm waters, it can be inferred that they interacted with the minke whales at lower latitudes. These findings may have important implications for our understanding of minke whale populations in the Salish Sea and the management of this species in the North Pacific

Averaging For Solitons With Nonlinearity Management

We develop an averaging method for solitons of the nonlinear Schr{\"o}dinger equation with periodically varying nonlinearity coefficient. This method is used to effectively describe solitons in Bose-Einstein condensates, in the context of the recently proposed and experimentally realizable technique of Feshbach resonance management. Using the derived local averaged equation, we study matter-wave bright and dark solitons and demonstrate a very good agreement between solutions of the averaged and full equations.Comment: 6 pages, 5 figures, in pres

Sample preparation: a crucial factor for the analytical performance of rationally designed MALDI matrices

Evidence is presented that the performance of the rationally designed MALDI matrix 4-chloro-α-cyanocinnamic acid (ClCCA) in comparison to its well-established predecessor α-cyano-4-hydroxycinnamic acid (CHCA) is significantly dependent on the sample preparation, such as the choice of the target plate. In this context, it becomes clear that any rational designs of MALDI matrices and their successful employment have to consider a larger set of physicochemical parameters, including sample crystallization and morphology/topology, in addition to parameters of basic (solution and/or gas-phase) chemistry

SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation

SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective therapeutics. Here we discover that SARS-CoV-2 replicates rapidly in lung epithelial cells despite triggering a robust innate immune response through activation of cytoplasmic RNA-sensors RIG-I and MDA5. The inflammatory mediators produced during epithelial cell infection can stimulate primary human macrophages to enhance cytokine production and drive cellular activation. Critically, this can be limited by abrogating RNA sensing, or by inhibiting downstream signalling pathways. SARS-CoV-2 further exacerbates the local inflammatory environment when macrophages or epithelial cells are primed with exogenous inflammatory stimuli. We propose that RNA sensing of SARS-CoV-2 in lung epithelium is a key driver of inflammation, the extent of which is influenced by the inflammatory state of the local environment, and that specific inhibition of innate immune pathways may beneficially mitigate inflammation-associated COVID-19