Multiple Independent Retroelement Insertions in the Promoter of a Stress Response Gene Have Variable Molecular and Functional Effects in Drosophila

[Abstract] Promoters are structurally and functionally diverse gene regulatory regions. The presence or absence of sequence motifs and the spacing between the motifs defines the properties of promoters. Recent alternative promoter usage analyses in Drosophila melanogaster revealed that transposable elements significantly contribute to promote diversity. In this work, we analyzed in detail one of the transposable element insertions, named FBti0019985, that has been co-opted to drive expression of CG18446, a candidate stress response gene. We analyzed strains from different natural populations and we found that besides FBti0019985, there are another eight independent transposable elements inserted in the proximal promoter region of CG18446. All nine insertions are solo-LTRs that belong to the roo family. We analyzed the sequence of the nine roo insertions and we investigated whether the different insertions were functionally equivalent by performing 5’-RACE, gene expression, and cold-stress survival experiments. We found that different insertions have different molecular and functional consequences. The exact position where the transposable elements are inserted matters, as they all showed highly conserved sequences but only two of the analyzed insertions provided alternative transcription start sites, and only the FBti0019985 insertion consistently affects CG18446 expression. The phenotypic consequences of the different insertions also vary: only FBti0019985 was associated with cold-stress tolerance. Interestingly, the only previous report of transposable elements inserting repeatedly and independently in a promoter region in D. melanogaster, were also located upstream of a stress response gene. Our results suggest that functional validation of individual structural variants is needed to resolve the complexity of insertion clusters.[Author Summary] The presence of several transposable element insertions in the promoter region of a Drosophila melanogaster gene has only been described in heat shock protein genes. In this work, we have discovered and characterized in detail several naturally occurring independent transposable element insertions in the promoter region of a cold-stress response gene in the fruitfly Drosophila melanogaster. The nine transposable element insertions described are clustered in a small 368 bp region and all belong to the same family of transposable elements: the roo family. Each individual insertion is present at relatively low population frequencies, ranging from 1% to 17%. However, the majority of strains analyzed contain one of these nine roo insertions suggesting that this region might be evolving under positive selection. Although the sequence of these insertions is highly similar, their molecular and functional consequences are different. Only one of them, FBti0019985, is associated with increased viability in nonstress and in cold-stress conditions.This work was supported by the Ministerio de Economía y Competitividad (MINECO: http://www.idi.mineco.gob.es) BFU-2011-24397 and RYC-2010-07306 to JG, and BES-2012-052999 to AU, Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (MINECO/FEDER:http://www.idi.mineco.gob.es) BFU2014-57779-P, the European Commission (https://ec.europa.eu) FP7-PEOPLE-2011-CIG-293860, the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (http://agaur.gencat.cat) 2014-SGR-201 to JG, and by the Agence Nationale de la Recherche (http://www.agence-nationale-recherche.fr) ANR-14-CE02-0003 to MARdC.USD 2250 APC fee funded by the EC FP7 Post-Grant Open Access PilotPeer reviewe

Adaptive Boolean Networks and Minority Games with Time--Dependent Capacities

In this paper we consider a network of boolean agents that compete for a limited resource. The agents play the so called Generalized Minority Game where the capacity level is allowed to vary externally. We study the properties of such a system for different values of the mean connectivity $K$ of the network, and show that the system with K=2 shows a high degree of coordination for relatively large variations of the capacity level.Comment: 4 pages, 4 figure

Statistical mechanics of the mixed majority-minority game with random external information

We study the asymptotic macroscopic properties of the mixed majority-minority game, modeling a population in which two types of heterogeneous adaptive agents, namely ``fundamentalists'' driven by differentiation and ``trend-followers'' driven by imitation, interact. The presence of a fraction f of trend-followers is shown to induce (a) a significant loss of informational efficiency with respect to a pure minority game (in particular, an efficient, unpredictable phase exists only for f<1/2), and (b) a catastrophic increase of global fluctuations for f>1/2. We solve the model by means of an approximate static (replica) theory and by a direct dynamical (generating functional) technique. The two approaches coincide and match numerical results convincingly.Comment: 19 pages, 3 figure

Multidisciplinary investigations using historical data, specific experimental surveys, numerical simulations and earthquake data to assess seismic hazard in a densely urbanized city: the study case of Palermo

The city of Palermo (southern Italy) was severely damaged in the past by moderate-magnitude earthquakes located tens of kilometres offshore. The historical monumental heritage and the high density of population motivated large efforts for the seismic risk assessment. We present the geological and seismological studies performed in downtown Palermo as a study case to show how the complexity of an urban environment can be approached with multidisciplinary investigations. Downtown Palermo is characterized by sea deposits in the coastal zone and the alluvial deposits of two rivers (Papireto and Kemonia) of about 150 m width, which were buried and filled during the XVII century. The difficulty of surface geological surveys was compensated through an analysis of aerial photos and more than 2000 borehole data organized in the City-GIS of the Department of Geology and Geodesy of the University of Palermo. A previous study on the well-documented historical damage indicated the major role played by the two river valleys and the sea deposits in controlling the damage distribution, above the assumption of a fairly homogeneous vulnerability of the existing buildings in downtown. To test the feasibility of using ambient noise for recognizing the presence of alluvial deposits in a densely urbanized environment, a large microtremor measurement campaign was performed in Palermo across several profiles. The frequency peaks inferred from the horizontal-to-vertical spectral ratio were compared with numerical simulations to assess the seismic velocity profile and the soil stratigraphy. Moreover, noise data were analyzed through a statistical approach to establish a possible correlation between damage, resonance frequency and amplitude, and geology. After the moderate earthquake of September 6, 2002 (Mw=5.9, 50 km far away), the analysis of the aftershock sequence provided a well documented estimate of the variation of ground motion within the city in the case of linear soil response. Using these aftershocks we computed also synthetic accelerograms of the main shock through Empirical Green’s Functions that provided ground accelerations as large as 50 gals, consistently with the documented EMS-98 intensity. Synthetic accelerograms showed a large variability of horizontal ground motion within the city (a factor of 3 – 4) that confirms the role of local geology in causing an increase of the seismic hazard on sea and alluvial deposits. Finally, we discuss the comparison between the acceleration response spectra calculated for different soil categories and the design elastic spectra provided by EC8

Strongyloides venezuelensis: efeito de antimicrobiano e imunossupressor no curso da infecção em camundongos da linhagem AKR/J

Groups of AKR/J strain of mice infected by Strongyloides venezuelensis and treated with Ceftazidima, Dexametasona or with both drugs concomitantly had been killed on 3rd, 7th and 12th day after infection and their lungs and intestines were processed for histological studies. In lungs of all infected groups, it was verified an inflammatory infiltrated (neutrophils and mononuclear cells) in the third day after the infection. In 7th and 12th day after the infection, the inflammatory reaction becomes reduced in control and antimicrobial treated groups, but not in immunosuppressed animals (with or without antimicrobial treatment). Analysis of the duodenal mucosa confirmed the presence of parasites in all groups of animals. On the 7th day after infection it was observed significant alterations in the small intestine of control (infected) and infected and treated with antimicrobial groups with presence of inflammatory foci, constituted by mononuclear and eosinophils in mucosa, associate to a large amount of parasites, mainly in the region of the epithelium and sub epithelium. Two others groups (infected and immunosuppressed mice with or without antimicrobial), did not present inflammatory process. Goblet cells were less evident in mucosa suggesting a reduction in mucous production. In the 12th day of the infection, the treated with antimicrobial and control groups presented a reduced number of parasites and a discrete inflammatory reaction in the small intestine while the immunosuppressed groups showed more parasites in duodenum. The permanence of the infection by S. venezuelensis in immunosuppressed animals was prolonged in relation to other groups, remaining until the 49th day after infection. The results indicate that the interference of treatments in the population of intestinal microbiota favours the parasitism by Strongyloides venezuelensis.Camundongos da linhagem AKR/J infectados pelo Strongyloides venezuelensis e tratados com Ceftazidima, Dexametasona ou com ambas as drogas foram sacrificados no terceiro, sétimo e décimo segundo dia após infecção. Pulmões e intestino delgado foram processados para histologia. Verificaram-se, nos pulmões dos quatro grupos infectados, infiltrados inflamatórios (neutrófilos e mononucleares) no terceiro dia após a infecção. No sétimo e décimo segundo dia após a infecção, o processo inflamatório se torna reduzido nos animais controle e tratados com antimicrobiano, mas não nos animais imunossuprimidos (com ou sem tratamento com antimicrobiano). A análise da mucosa duodenal confirmou a presença de parasitos em todos os grupos de animais. No 7º dia após a infecção, foram observadas alterações significativas no duodeno dos grupos controle (infectados) e dos infectados e tratados com antimicrobiano, com presença de infiltrado inflamatório, constituído de mononucleares e eosinófilos na mucosa, associada a uma maior quantidade de parasitos, principalmente na região do epitélio e sub-epitélio. Os outros dois grupos (camundongos infectados e imunossuprimidos com ou sem antimicrobiano), não apresentaram processo inflamatório. A mucosa apresentou células caliciformes menos evidentes, sugerindo uma redução de produção de muco. No décimo segundo dia da infecção, os grupos não tratados e tratados apenas com antimicrobiano apresentaram um número reduzido de parasitos e um discreto processo inflamatório no duodeno, enquanto os grupos tratados com imunossupressor (com ou sem antimicrobiano) mostraram presença de um maior número do parasito no duodeno. A permanência da infecção do S. venezuelensis foi mais prolongada nos animais imunossuprimidos em relação aos demais grupos, permanecendo até o 490dia após infecção. Os resultados indicam que a interferência dos tratamentos no equilíbrio da microbiota intestinal favoreceu o parasitismo pelo S. venezuelensis

Empirical evaluation of microtremor H/V spectral ratio

The objective of this work is to perform a purely empirical assessment of the actual capabilities of the horizontal-to-vertical (H/V) spectral ratio technique to provide reliable and relevant information concerning site conditions and/or site amplification. This objective has been tackled through the homogeneous (re)processing of a large volume of earthquakes and ambient noise data recorded by different research teams in more than 200 sites located mainly in Europe, but also in the Caribbean and in Tehran. The original recordings were first gathered in a specific database with information on both the sites and recorded events. Then, for all sites close to an instrumented reference, average site-to-reference spectral ratios (“spectral ratio method” (SSR)) were derived in a homogeneous way (window selection, smoothing, signal-to-noise ratio threshold, averaging), as well as H/V ratios (“HVSRE–RF”) on earthquake recordings. H/V ratios were also obtained from noise recordings at each site (either specific measurements, or extracted from pre- or post-event noise windows). The spectral curves resulting from these three techniques were estimated reliable for a subset of 104 sites, and were thus compared in terms of fundamental frequency, amplitude and amplification bandwidth, exhibiting agreements and disagreements, for which interpretations are looked for in relation with characteristics of site conditions. The first important result consists in the very good agreement between fundamental frequencies obtained with either technique, observed for 81% of the analyzed sites. A significant part of the disagreements correspond to thick, low frequency, continental sites where natural noise level is often very low and H/V noise ratios do not exhibit any clear peak. The second important result is the absence of correlation between H/V peak amplitude and the actual site amplification measured on site-to-reference spectral ratios. There are, however, two statistically significant results about the amplitude of the H/V curve: the peak amplitude may be considered as a lower bound estimate of the actual amplification indicated by SSR (it is smaller for 79% of the 104 investigated sites), and, from another point of view, the difference in amplitude exhibits a questioning correlation with the geometrical characteristics of the sediment/basement interface: large SSR/HV differences might thus help to detect the existence of significant 2D or 3D effects.Published75-1084.1. Metodologie sismologiche per l'ingegneria sismicaJCR Journalreserve

ZEUS Next-to-leading-order QCD Analysis of Data on Deep Inelastic Scattering

Next-to-leading-order QCD analyses of the ZEUS data on deep inelastic scattering together with fixed-target data have been performed, from which the gluon and quark densities of the proton and the value of the strong coupling constant (Formula presented) were extracted. The study includes a full treatment of the experimental systematic uncertainties including point-to-point correlations. The resulting uncertainties in the parton density functions are presented. A combined fit for (Formula presented) and the gluon and quark densities yields a value for (Formula presented) in agreement with the world average. The parton density functions derived from ZEUS data alone indicate the importance of HERA data in determining the sea quark and gluon distributions at low x. The limits of applicability of the theoretical formalism have been explored by comparing the fit predictions to ZEUS data at very low (Formula presented) © 2003 The American Physical Society

Jet production in charged current deep inelastic e⁺p scatteringat HERA

The production rates and substructure of jets have been studied in charged current deep inelastic e⁺p scattering for Q² > 200 GeV² with the ZEUS detector at HERA using an integrated luminosity of 110.5 pb⁻¹. Inclusive jet cross sections are presented for jets with transverse energies E_{T}^{jet} > 5 GeV. Measurements of the mean subjet multiplicity, 〈n_{sbj}〉, of the inclusive jet sample are presented. Predictions based on parton-shower Monte Carlo models and next-to-leading-order QCD calculations are compared to the measurements. The value of α_{s} (M_{z}), determined from 〈n_{sbj}〉 at y_{cut} = 10⁻² for jets with 25 < E_{T}^{jet} < 119 GeV, is α_{s} (M_{z}) = 0.1202 ± 0.0052 (stat.)_{-0.0019}^{+0.0060} (syst.)_{-0.0053}^{+0.0065} (th.). The mean subjet multiplicity as a function of Q² is found to be consistent with that measured in NC DIS