Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes

Regulatory landscapes drive complex developmental gene expression, but it remains unclear how their integrity is maintained when incorporating novel genes and functions during evolution. Here, we investigated how a placental mammal-specific gene, Zfp42, emerged in an ancient vertebrate topologically associated domain (TAD) without adopting or disrupting the conserved expression of its gene, Fat1. In ESCs, physical TAD partitioning separates Zfp42 and Fat1 with distinct local enhancers that drive their independent expression. This separation is driven by chromatin activity and not CTCF/cohesin. In contrast, in embryonic limbs, inactive Zfp42 shares Fat1’s intact TAD without responding to active Fat1 enhancers. However, neither Fat1 enhancer-incompatibility nor nuclear envelope-attachment account for Zfp42’s unresponsiveness. Rather, Zfp42’s promoter is rendered inert to enhancers by context-dependent DNA methylation. Thus, diverse mechanisms enabled the integration of independent Zfp42 regulation in the Fat1 locus. Critically, such regulatory complexity appears common in evolution as, genome wide, most TADs contain multiple independently expressed genes.We thank the Montpellier Ressources Imagerie facility (BioCampus Montpellier, Centre National de la Recherche Scientifique [CNRS], INSERM, University of Montpellier) and for computer resources from CINECA (ISCRA grant thanks to computer resources from INFN and CINECA [ISCRA Grant HP10C8JWU7]). G.C., Q.S., and F.B. were supported by a grant from the European Research Council (Advanced Grant 3DEpi, 788972) and by the CNRS. This work was funded by EMBO and the Wellcome Trust (ALTF1554-2016 and 206475/Z/17/Z; to M.I.R.) as well as the Deutsche Forschungsgemeinschaft (KR3985/7-3 and MU 880/16-1 to S.M.)

Here and now: perceptions of Indian Ocean islanders on the climate change and migration nexus

Empirical studies exploring the links between climate change and migration are increasing. Often, perceptions are not fully explored from the people most affected by the climate change and migration nexus. This article contributes to filling this gap by eliciting and analyzing perceptions regarding climate change and migration from an understudied population labelled as being amongst those most immediately and directly affected by climate change: Indian Ocean islanders. Open-ended, semi-structured interviews were conducted in two case study communities in Maldives (Kaafu Guraidhoo with 17 interviews and Raa Dhuvafaaru with 18 interviews) and two case study communities in Lakshadweep, India (Kavaratti with 35 interviews and Minicoy with 26 interviews). The results present the interviewees’ perceptions of climatic variability and change that they experience; how they perceive the causes of these changes; and links to migration decisions. The interviews demonstrate that perceptions of climate change, of migration, and of the links or lack thereof between the two are centred on the interviewees’ own experiences, their own locations, and the immediate timeframe. External information and direction has limited influence. Their perceptions are framed as being the ‘here and now’ through topophilia (here) and tempophilia (now). The islanders’ views do not avoid, but rather encompass, long-term livelihoods and the future. Such a future might be in another location, but the anchor is expressing future hopes and aspirations through the here and now. It is not linked to the wide-scale, long-term issue of climate change

The 1430s: a cold period of extraordinary internal climate variability during the early Spörer Minimum with social and economic impacts in north-western and central Europe

Changes in climate affected human societies throughout the last millennium. While European cold periods in the 17th and 18th century have been assessed in detail, earlier cold periods received much less attention due to sparse information available. New evidence from proxy archives, historical documentary sources and climate model simulations permit us to provide an interdisciplinary, systematic assessment of an exceptionally cold period in the 15th century. Our assessment includes the role of internal, unforced climate variability and external forcing in shaping extreme climatic conditions and the impacts on and responses of the medieval society in north-western and central Europe. Climate reconstructions from a multitude of natural and anthropogenic archives indicate that the 1430s were the coldest decade in north-western and central Europe in the 15th century. This decade is characterised by cold winters and average to warm summers resulting in a strong seasonal cycle in temperature. Results from comprehensive climate models indicate consistently that these conditions occurred by chance due to the partly chaotic internal variability within the climate system. External forcing like volcanic eruptions tends to reduce simulated temperature seasonality and cannot explain the reconstructions. The strong seasonal cycle in temperature reduced food production and led to increasing food prices, a subsistence crisis and a famine in parts of Europe. Societies were not prepared to cope with failing markets and interrupted trade routes. In response to the crisis, authorities implemented numerous measures of supply policy and adaptation such as the installation of grain storage capacities to be prepared for future food production shortfalls

Large-scale mapping of mutations affecting zebrafish development

BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the mutagen ENU have isolated several hundred mutant loci that represent putative developmental control genes. In order to realize the potential of such screens, systematic genetic mapping of the mutations is necessary. Here we report on a large-scale effort to map the mutations generated in mutagenesis screening at the Max Planck Institute for Developmental Biology by genome scanning with microsatellite markers. RESULTS: We have selected a set of microsatellite markers and developed methods and scoring criteria suitable for efficient, high-throughput genome scanning. We have used these methods to successfully obtain a rough map position for 319 mutant loci from the Tübingen I mutagenesis screen and subsequent screening of the mutant collection. For 277 of these the corresponding gene is not yet identified. Mapping was successful for 80 % of the tested loci. By comparing 21 mutation and gene positions of cloned mutations we have validated the correctness of our linkage group assignments and estimated the standard error of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map positions for over 300 zebrafish loci with developmental phenotypes, we have generated a dataset that will be useful not only for cloning of the affected genes, but also to suggest allelism of mutations with similar phenotypes that will be identified in future screens. Furthermore this work validates the usefulness of our methodology for rapid, systematic and inexpensive microsatellite mapping of zebrafish mutations

Sustaining modified behaviours learnt in a diabetes prevention program in regional Australia : the role of social context

BackgroundThe Greater Green Triangle diabetes prevention program was conducted in primary health care setting of Victoria and South Australia in 2004--2006. This program demonstrated significant reductions in diabetes risk factors which were largely sustained at 18 month follow-up. The theoretical model utilised in this program achieved its outcomes through improvements in coping self-efficacy and planning. Previous evaluations have concentrated on the behavioural components of the intervention. Other variables external to the main research design may have contributed to the success factors but have yet to be identified. The objective of this evaluation was to identify the extent to which participants in a diabetes prevention program sustained lifestyle changes several years after completing the program and to identify contextual factors that contributed to sustaining changes.MethodsA qualitative evaluation was conducted. Five focus groups were held with people who had completed a diabetes prevention program, several years later to assess the degree to which they had sustained program strategies and to identify contributing factors.ResultsParticipants value the recruitment strategy. Involvement in their own risk assessment was a strong motivator. Learning new skills gave participants a sense of empowerment. Receiving regular pathology reports was a means of self-assessment and a motivator to continue. Strong family and community support contributed to personal motivation and sustained practice.ConclusionsFamily and local community supports constitute the contextual variables reported to contribute to sustained motivation after the program was completed. Behaviour modification programs can incorporate strategies to ensure these factors are recognised and if necessary, strengthened at the local level.<br /

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file