Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis

The initiation of mammalian puberty and the maintenance of female reproductive cycles are events controlled by hypothalamic neurons that secrete the decapeptide gonadotropin-releasing hormone (GnRH). GnRH secretion is, in turn, controlled by changes in neuronal and glial inputs to GnRH-producing neurons. The hierarchical control of the process is unknown, but it requires coordinated regulation of these cell-cell interactions. Here we report the functional characterization of a gene (termed enhanced at puberty 1 [EAP1]) that appears to act as an upstream transcriptional regulator of neuronal networks controlling female reproductive function. EAP1 expression increased selectively at puberty in both the nonhuman primate and rodent hypothalamus. EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity. Inhibition of EAP1 expression, targeted to the rodent hypothalamus via lentivirus-mediated delivery of EAP1 siRNAs, delayed puberty, disrupted estrous cyclicity, and resulted in ovarian abnormalities. These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.This work was supported by grants from the NIH, the National Institute of Child Health and Human Development/NIH (to S.R. Ojeda), the European Society for Paediatric Endocrinology (to H. Jung), the German Research Foundation (to S. Heger), and the European Commission (PIONEER to S. Heger)

Evolution of mobility governance in Flanders: opening up for bottom-up initiatives or suffering from lock-in?

Mobility policy in Flanders lacks a clear discourse on implementing the policy objectives for 2020 and beyond. Though mobility planning can show success stories, mobility problems seem to aggravate. For supra local mobility projects in Flanders the executive power often lies with deconcentrated administrations at the level of the province, this is e.g. the case for public transportation and major roads, where province boundaries impede public transport projects across borders. For local mobility plans, the local administration and council have the power. But as these local mobility plans have highly formalised procedures, they tend to be rigid frameworks or administrations and risk to be suffering from lock-in. There is a need for new dynamics in mobility policy in reference to present developments. Here bottom-up or outside-in initiatives can be regarded as the key to real change. To that end radical changes in the organisation and mobility planning itself are necessary to meet these new inititiaves from the bottum-up and outside-in. Next to hardware and software approaches or innovations to turn mobility planning more sustainable, we additionally propose in this paper an ‘orgware’ solution, demonstrated in some case studies. In these cases key actors of bottom-up projects and their associations with other actors are visualised. Furthermore barriers and potentials for implementation are formulated leading onto recommendations for further research in order to improve the implementation of the policy objectives

Measuring information-transfer delays

In complex networks such as gene networks, traffic systems or brain circuits it is important to understand how long it takes for the different parts of the network to effectively influence one another. In the brain, for example, axonal delays between brain areas can amount to several tens of milliseconds, adding an intrinsic component to any timing-based processing of information. Inferring neural interaction delays is thus needed to interpret the information transfer revealed by any analysis of directed interactions across brain structures. However, a robust estimation of interaction delays from neural activity faces several challenges if modeling assumptions on interaction mechanisms are wrong or cannot be made. Here, we propose a robust estimator for neuronal interaction delays rooted in an information-theoretic framework, which allows a model-free exploration of interactions. In particular, we extend transfer entropy to account for delayed source-target interactions, while crucially retaining the conditioning on the embedded target state at the immediately previous time step. We prove that this particular extension is indeed guaranteed to identify interaction delays between two coupled systems and is the only relevant option in keeping with Wiener’s principle of causality. We demonstrate the performance of our approach in detecting interaction delays on finite data by numerical simulations of stochastic and deterministic processes, as well as on local field potential recordings. We also show the ability of the extended transfer entropy to detect the presence of multiple delays, as well as feedback loops. While evaluated on neuroscience data, we expect the estimator to be useful in other fields dealing with network dynamics

Animal cell cytokinesis: the role of dynamic changes in the plasma membrane proteome and lipidome

In animal cells, cytokinesis is characterised by the formation of the mitotic spindle that signals the assembly of an actomyosin ring between the spindle poles. Contraction of this ring drives ingression of the cleavage furrow, and culminates in the formation of a thin intercellular bridge between the daughter cells. At the centre of this bridge is the midbody, which is thought both to provide a site of attachment for the plasma membrane furrow and act as foci for the spatial and temporal control mechanisms that drive abscission. This review will focus upon recent studies that offer new insight into these events, in particular studies that elaborate on the mechanism of attachment between the furrow plasma membrane and the underlying cytoskeleton, and how dynamic changes in membrane composition might underpin key aspects of cytokinesis

Beta-delayed proton emission in the 100Sn region

Beta-delayed proton emission from nuclides in the neighborhood of 100Sn was studied at the National Superconducting Cyclotron Laboratory. The nuclei were produced by fragmentation of a 120 MeV/nucleon 112Sn primary beam on a Be target. Beam purification was provided by the A1900 Fragment Separator and the Radio Frequency Fragment Separator. The fragments of interest were identified and their decay was studied with the NSCL Beta Counting System (BCS) in conjunction with the Segmented Germanium Array (SeGA). The nuclei 96Cd, 98Ing, 98Inm and 99In were identified as beta-delayed proton emitters, with branching ratios bp = 5.5(40)%, 5.5+3 -2%, 19(2)% and 0.9(4)%, respectively. The bp for 89Ru, 91,92Rh, 93Pd and 95Ag were deduced for the first time with bp = 3+1.9 -1.7%, 1.3(5)%, 1.9(1)%, 7.5(5)% and 2.5(3)%, respectively. The bp = 22(1)% for 101Sn was deduced with higher precision than previously reported. The impact of the newly measured bp values on the composition of the type-I X-ray burst ashes was studied.Comment: 15 pages, 14 Figures, 4 Table

Laser Chimeras as a paradigm for multi-stable patterns in complex systems

Chimera is a rich and fascinating class of self-organized solutions developed in high dimensional networks having non-local and symmetry breaking coupling features. Its accurate understanding is expected to bring important insight in many phenomena observed in complex spatio-temporal dynamics, from living systems, brain operation principles, and even turbulence in hydrodynamics. In this article we report on a powerful and highly controllable experiment based on optoelectronic delayed feedback applied to a wavelength tunable semiconductor laser, with which a wide variety of Chimera patterns can be accurately investigated and interpreted. We uncover a cascade of higher order Chimeras as a pattern transition from N to N - 1 clusters of chaoticity. Finally, we follow visually, as the gain increases, how Chimera is gradually destroyed on the way to apparent turbulence-like system behaviour.Comment: 7 pages, 6 figure