A Role for Methyl-CpG Binding Domain Protein 2 in the Modulation of the Estrogen Response of pS2/TFF1 Gene

Background: In human Estrogen Receptor alpha (ER alpha)-positive breast cancers, 59 end dense methylation of the estrogen-regulated pS2/TFF1 gene correlates with its transcriptional inhibition. However, in some ER alpha-rich biopsies, pS2 expression is observed despite the methylation of its TATA-box region. Herein, we investigated the methylation-dependent mechanism of pS2 regulation. Methodology/Principal Findings: We observed interplay between Methyl-CpG Binding Domain protein 2 (MBD2) transcriptional repressor and ER alpha transactivator: (i) the pS2 gene is poised for transcription upon demethylation limited to the enhancer region containing the estrogen responsive element (ERE); (ii) MBD2-binding sites overlapped with the methylation status of the pS2 59 end; (iii) MBD2 depletion elevated pS2 expression and ectopic expression of ER alpha partially overcame the inhibitory effect of MBD2 when the ERE is unmethylated. Furthermore, serial chromatin immunoprecipitation assays indicated that MBD2 and ER alpha could simultaneously occupy the same pS2 DNA molecule; (iv) concomitant ectopic ER alpha expression and MBD2 depletion resulted in synergistic transcriptional stimulation, while the pS2 promoter remains methylated. Conclusions/Significance: MBD2 and ER alpha drive opposite effects on pS2 expression, which are associated with specific steady state levels of histone H3 acetylation and methylation marks. Thus, epigenetic silencing of pS2 could be dependent on balance of the relative intracellular concentrations of ER alpha and MBD2

A Role for Methyl-CpG Binding Domain Protein 2 in the Modulation of the Estrogen Response of pS2/TFF1 Gene

In human Estrogen Receptor alpha (ERalpha)-positive breast cancers, 5' end dense methylation of the estrogen-regulated pS2/TFF1 gene correlates with its transcriptional inhibition. However, in some ERalpha-rich biopsies, pS2 expression is observed despite the methylation of its TATA-box region. Herein, we investigated the methylation-dependent mechanism of pS2 regulation.We observed interplay between Methyl-CpG Binding Domain protein 2 (MBD2) transcriptional repressor and ERalpha transactivator: (i) the pS2 gene is poised for transcription upon demethylation limited to the enhancer region containing the estrogen responsive element (ERE); (ii) MBD2-binding sites overlapped with the methylation status of the pS2 5' end; (iii) MBD2 depletion elevated pS2 expression and ectopic expression of ERalpha partially overcame the inhibitory effect of MBD2 when the ERE is unmethylated. Furthermore, serial chromatin immunoprecipitation assays indicated that MBD2 and ERalpha could simultaneously occupy the same pS2 DNA molecule; (iv) concomitant ectopic ERalpha expression and MBD2 depletion resulted in synergistic transcriptional stimulation, while the pS2 promoter remains methylated.MBD2 and ERalpha drive opposite effects on pS2 expression, which are associated with specific steady state levels of histone H3 acetylation and methylation marks. Thus, epigenetic silencing of pS2 could be dependent on balance of the relative intracellular concentrations of ERalpha and MBD2

On the Transferability of Neural Models of Morphological Analogies

International audienceAnalogical proportions are statements expressed in the form "A is to B as C is to D" and are used for several reasoning and classification tasks in artificial intelligence and natural language processing (NLP). In this paper, we focus on morphological tasks and we propose a deep learning approach to detect morphological analogies. We present an empirical study to see how our framework transfers across languages, and that highlights interesting similarities and differences between these languages. In view of these results, we also discuss the possibility of building a multilingual morphological model

A Neural Approach for Detecting Morphological Analogies

International audienc

A Neural Approach for Detecting Morphological Analogies

International audienceAnalogical proportions are statements of the form "A is to B as C is to D" that are used for several reasoning and classification tasks in artificial intelligence and natural language processing (NLP). For instance, there are analogy based approaches to semantics as well as to morphology. In fact, symbolic approaches were developed to solve or to detect analogies between character strings, e.g., the axiomatic approach as well as that based on Kolmogorov complexity. In this paper, we propose a deep learning approach to detect morphological analogies, for instance, with reinflexion or conjugation. We present empirical results that show that our framework is competitive with the above-mentioned state of the art symbolic approaches. We also explore empirically its transferability capacity across languages, which highlights interesting similarities between them

Noninvasive western lowland gorilla's health monitoring: A decade of simian immunodeficiency virus surveillance in southern Cameroon.

Simian immunodeficiency virus (SIVgor) causes persistent infection in critically endangered western lowland gorillas (Gorilla gorilla gorilla) from west central Africa. SIVgor is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively). We established a noninvasive method that does not interfere with gorillas' natural behaviour to provide wildlife pathogen surveillance and health monitoring for conservation. A total of 1,665 geo-referenced fecal samples were collected at regular intervals from February 2006 to December 2014 (123 sampling days) in the Campo-Ma'an National Park (southwest Cameroon). Host genotyping was performed using microsatellite markers, SIVgor infection was identified by serology and genetic amplification was attempted on seropositive individuals. We identified at least 125 distinct gorillas, 50 were resampled (observed 3.5 times in average) and 38 were SIVgor+ (seven individuals were seroconverters). Six groups of gorillas were identified based on the overlapping occurrence of individuals with apparent high rates of gene flow. We obtained SIVgor genetic sequences from 25 of 38 seropositive genotyped gorillas and showed that the virus follows exponential growth dynamics under a strict molecular clock. Different groups shared SIVgor lineages demonstrating intergroup viral spread and recapture of positive individuals illustrated intra-host viral evolution. Relatedness and relationship genetic analysis of gorillas together with Bayesian phylogenetic inference of SIVgor provided evidence suggestive of vertical transmission. In conclusion, we provided insights into gorilla social dynamics and SIVgor evolution and emphasized the utility of noninvasive sampling to study wildlife health populations. These findings contribute to prospective planning for better monitoring and conservation

Zoonotic origin of the human malaria parasite Plasmodium malariae from African apes

The human parasite Plasmodium malariae has relatives infecting African apes (Plasmodium rodhaini) and New World monkeys (Plasmodium brasilianum), but its origins remain unknown. Using a novel approach to characterise P. malariae-related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae, but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum. In contrast, P. brasilianum falls within the radiation of human P. malariae, and thus reflects a recent anthroponosis.Peer Reviewe

Origin of the HIV-1 group O epidemic in western lowland gorillas

HIV-1, the cause of AIDS, is composed of four phylogenetic lineages, groups M, N, O, and P, each of which resulted from an independent cross-species transmission event of simian immunodeficiency viruses (SIVs) infecting African apes. Although groups M and N have been traced to geographically distinct chimpanzee communities in southern Cameroon, the reservoirs of groups O and P remain unknown. Here, we screened fecal samples fromwestern lowland (n = 2,611), eastern lowland (n = 103), and mountain (n = 218) gorillas for gorilla SIV (SIVgor) antibodies and nucleic acids. Despite testing wild troops throughout southern Cameroon (n = 14), northern Gabon (n = 16), the Democratic Republic of Congo (n = 2), and Uganda (n = 1), SIVgor was identified at only four sites in southern Cameroon, with prevalences ranging from 0.8-22%. Amplification of partial and full-length SIVgor sequences revealed extensive genetic diversity, but all SIVgor strains were derived from a single lineage within the chimpanzee SIV (SIVcpz) radiation. Two fully sequenced gorilla viruses from southwestern Cameroon were very closely related to, and likely represent the source population of, HIV-1 group P. Most of the genome of a third SIVgor strain, from central Cameroon, was very closely related to HIV-1 group O, again pointing to gorillas as the immediate source. Functional analyses identified the cytidine deaminase APOBEC3G as a barrier for chimpanzee-to-gorilla, but not gorilla-to-human, virus transmission. These data indicate that HIV-1 group O, which spreads epidemically in west central Africa and is estimated to have infected around 100,000 people, originated by cross-species transmission from western lowland gorillas

Current Wildland Fire Patterns and Challenges in Europe : A Synthesis of National Perspectives

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009-2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action "Fire and the Earth System: Science & Society" funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.Peer reviewe