Selective Activation of Alternative MYC Core Promoters by Wnt-Responsive Enhancers.

In Metazoans, transcription of most genes is driven by the use of multiple alternative promoters. Although the precise regulation of alternative promoters is important for proper gene expression, the mechanisms that mediates their differential utilization remains unclear. Here, we investigate how the two alternative promoters (P1, P2) that drive MYC expression are regulated. We find that P1 and P2 can be differentially regulated across cell-types and that their selective usage is largely mediated by distal regulatory sequences. Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation

Therapy for Irregular Menstruation with Acupunture and Herbal Pegagan (Centella Asiatica (L.))

Background : Menstruation is bleeding periodic scale and cyclical from uterus extrication (deskuamasi) endometrium. Menstruation bleeding is complex interaction result wich involve hormone system and body system, that are hypothalamus, hypofisis, ovarium and uterus. Every woman has different menstruation cycle. The causes of irregular menstruation are genetic and bad habit life. While according to TCM, irregular menstruation is Yue Jing Bu Tiao. Purpose : to knowing the effect of acupuncture therapy and point of Guanyuan (CV 4), Shenshu (BL 23), Sanyinjao (SP 6) and Shenmen (HT 7). Therapy was given 12 times, 3 times every week. Herbal therapy wich given was pegagan (Centella asiatica (L)) with dose 0,3 and consumed everyday after eat. Result : therapy that used acupuncture and herbal in irregular menstruation case showing menstruation cycle change, that was menstruation cycle became shorter from 76 days to 41 days. Conclusion : acupuncture therapy on point of Guanyuan (CV 4), Shenshu (BL 23), Sanyinjao (SP 6), Shenmen (HT 7), and pegagan herbal (Centella asiatica (L)) could shorten menstruation cycle from 76 days to 41 days

Dental Shape Variation and Phylogenetic Signal in the Rattini Tribe Species of Mainland Southeast Asia

We would like to thank Pierre-Henri Fabre for providing the phylogeny for this study. The collection of specimens used was funded by the French ANR Biodiversity, grant ANR 07 BDIV 012 CERoPath project (www.ceropath.org), and by the French ANR CP&ES, grant ANR 11 CPEL 002 BiodivHealthSEA project (www.biodivhealthsea.org). We also thank Madoudou Garba and Gauthier Dobigny (CBGP-IRD) for providing additional specimens. We greatly thank all local communities and their leaders for permission and invaluable help during field trapping. Special thanks to the CERoPath and BiodivHealthSEA teams and the drivers for their invaluable help during fieldwork. We would also like to thank Maeve McMahon for help with manuscript editing and preparation.Peer reviewedPublisher PD

Use of domesticated pigs by Mesolithic hunter-gatherers in northwestern Europe

Acknowledgements We thank the Archaeological State Museum Schleswig-Holstein, the Archaeological State Offices of Brandenburg, Lower Saxony and Saxony and the following individuals who provided sample material: Betty Arndt, Jo¨rg Ewersen, Frederick Feulner, Susanne Hanik, Ru¨diger Krause, Jochen Reinhard, Uwe Reuter, Karl-Heinz Ro¨hrig, Maguerita Scha¨fer, Jo¨rg Schibler, Reinhold Schoon, Regina Smolnik, Thomas Terberger and Ingrid Ulbricht. We are grateful to Ulrich Schmo¨lcke, Michael Forster, Peter Forster and Aikaterini Glykou for their support and comments on the manuscript. We also thank many institutions and individuals that provided sample material and access to collections, especially the curators of the Museum fu¨r Naturkunde, Berlin; Muse´um National d0 Histoire Naturelle, Paris; Smithsonian Institution, National Museum of Natural History, Washington D.C.; Zoologische Staatssammlung, Mu¨nchen; Museum fu¨r Haustierkunde, Halle; the American Museum of Natural History, New-York. This work was funded by the Graduate School ‘Human Development in Landscapes’ at Kiel University (CAU) and supported by NERC project Grant NE/F003382/1. Radiocarbon dating was carried out at the Leibniz Laboratory, CAU. This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs 3.0 Unported License.Peer reviewedPublisher PD

Evolution under intensive industrial breeding: skull size and shape comparison between historic and modern pig lineages

Domestication and subsequent human-induced selection has enhanced profound changes in animal morphology. On modern domestic pigs, those transformations encompass not only overall increases in body size but also modifications in skull morphology. While skull morphological differences between modern domestic pigs and wild boar are relatively well-documented, less understood is the variation and underlying mechanisms associated with intensive breeding. In this study, we investigated the rate and direction of phenotypic change of skull morphology using a unique dataset that includes two lineages of German domestic pig that were subjected to similar intensive industrial selection pressures throughout the twentieth century, alongside contemporaneous populations of German wild boar. Size and shape variation of 135 specimens was quantified through geometric morphometrics, with 82 three-dimensional landmarks. We find expected differences in skull shape between wild and domestic pigs, but also convergence between the two domestic lineages through the century of directed breeding, despite population segregation. Our results suggest that cranial morphologies have rapidly responded to selection pressure that is independent of genetic isolation. This also suggests that pig morphotypes quickly reflect human agency and impact upon domestic animal phenotypes, revealing a pathway to investigate early human breeding activity in ancient and historical contexts

European security in the 1990s and beyond : the implications of the accession of Cyprus and Malta to the European Union

For the last decade, the dramatic events in eastern and central Europe have (rightly) dominated the security debate in Europe and, indeed, the wider world. One of the consequences of this has been that the traditional neglect of the Mediterranean region has been compounded. However, there are now signs-notably the recent Barcelona conference at which the European Union's Mediterranean policy was relaunched and extended (to incorporate the grand design of a Mediterranean free trade area) - that the Mediterranean is, at last, receiving some of the attention it deserves and justifies.peer-reviewe

A doubly stochastic rainfall model with exponentially decaying pulses

We develop a doubly stochastic point process model with exponentially decaying pulses to describe the statistical properties of the rainfall intensity process. Mathematical formulation of the point process model is described along with second-order moment characteristics of the rainfall depth and aggregated processes. The derived second-order properties of the accumulated rainfall at different aggregation levels are used in model assessment. A data analysis using 15 years of sub-hourly rainfall data from England is presented. Models with fixed and variable pulse lifetime are explored. The performance of the model is compared with that of a doubly stochastic rectangular pulse model. The proposed model fits most of the empirical rainfall properties well at sub-hourly, hourly and daily aggregation levels

Singular patterns of skull shape and brain size change in the domestication of South American camelids

Patterns of selection in South American camelids (Lamini) and their unique demographic history establish the llama and alpaca as remarkable cases of domestication among large herd animals. Skull shape is implicated in many changes reported between wild and domestic taxa. We apply 3D geometric morphometric methods to describe skull shape, form, and size, differences among the four species of Lamini. In so doing, we test if domesticated Lamini exhibit changes similar to those in other domesticated groups: not only in the skull, but also in brain and body size. In contrast to other domesticated artiodactyls, very little change has occurred in domestic alpacas and llamas compared to their wild counterparts. Nevertheless, their differences are statistically significant and include a flatter cranium, inclined palate and increased airorhynchy in the domestics. Selection pressures that contrast with those on other herd animals, as well as recent population bottlenecks, likely have influenced the morphological patterns we note in Lamini. High-resolution 3D morphospace allows skull size, shape, and form (shape + size), to discriminate all four species, with form providing the greatest separation. These results help differentiate morphologically the Lamini, which in nature are distinguished mainly by body size, and provide an additional tool to archaeologists for distinction of wild and domestic remains. Most of our shape analyses suggest a marginally closer relationship between the alpaca and vicuña, to the exclusion of the guanaco, supporting the genetic relationships for this group. The expected brain size change between wild and domestic populations is lower than previously thought, with a 15.4% reduction in llama, and 6.8% reduction in alpaca. This is the lowest reduction in brain size thus far reported among domesticated Artiodactyla