Transcription-coupled deposition of histone modifications during MHC class II gene activation

Posttranslational histone modifications associated with actively expressed genes are generally believed to be introduced primarily by histone-modifying enzymes that are recruited by transcription factors or their associated co-activators. We have performed a comprehensive spatial and temporal analyses of the histone modifications that are deposited upon activation of the MHC class II gene HLA-DRA by the co-activator CIITA. We find that transcription-associated histone modifications are introduced during two sequential phases. The first phase precedes transcription initiation and is characterized exclusively by a rapid increase in histone H4 acetylation over a large upstream domain. All other modifications examined, including the acetylation and methylation of several residues in histone H3, are restricted to short regions situated at or within the 5′ end of the gene and are established during a second phase that is concomitant with ongoing transcription. This second phase is completely abrogated when elongation by RNA polymerase II is blocked. These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activatio

Discourse-aware rumour stance classification in social media using sequential classifiers

Rumour stance classification, defined as classifying the stance of specific social media posts into one of supporting, denying, querying or commenting on an earlier post, is becoming of increasing interest to researchers. While most previous work has focused on using individual tweets as classifier inputs, here we report on the performance of sequential classifiers that exploit the discourse features inherent in social media interactions or 'conversational threads'. Testing the effectiveness of four sequential classifiers -- Hawkes Processes, Linear-Chain Conditional Random Fields (Linear CRF), Tree-Structured Conditional Random Fields (Tree CRF) and Long Short Term Memory networks (LSTM) -- on eight datasets associated with breaking news stories, and looking at different types of local and contextual features, our work sheds new light on the development of accurate stance classifiers. We show that sequential classifiers that exploit the use of discourse properties in social media conversations while using only local features, outperform non-sequential classifiers. Furthermore, we show that LSTM using a reduced set of features can outperform the other sequential classifiers; this performance is consistent across datasets and across types of stances. To conclude, our work also analyses the different features under study, identifying those that best help characterise and distinguish between stances, such as supporting tweets being more likely to be accompanied by evidence than denying tweets. We also set forth a number of directions for future research

The Lyot Project Direct Imaging Survey of Substellar Companions: Statistical Analysis and Information from Nondetections

The Lyot project used an optimized Lyot coronagraph with Extreme Adaptive Optics at the 3.63m Advanced Electro-Optical System telescope (AEOS) to observe 86 stars from 2004 to 2007. In this paper we give an overview of the survey results and a statistical analysis of the observed nondetections around 58 of our targets to place constraints on the population of substellar companions to nearby stars. The observations did not detect any companion in the substellar regime. Since null results can be as important as detections, we analyzed each observation to determine the characteristics of the companions that can be ruled out. For this purpose we use a Monte Carlo approach to produce artificial companions, and determine their detectability by comparison with the sensitivity curve for each star. All the non-detection results are combined using a Bayesian approach and we provide upper limits on the population of giant exoplanets and brown dwarfs for this sample of stars. Our nondetections confirm the rarity of brown dwarfs around solar-like stars and we constrain the frequency of massive substellar companions (M>40Mjup) at orbital separation between and 10 and 50 AU to be <20%.Comment: 32 pages, 11 figures, 2 tables. Published in the Astrophysical Journa

Status of the Micro Vertex Detector of the Compressed Baryonic Matter Experiment

The CBM experiment will investigate heavy-ion collisions at beam energies from 8 to 45 AGeV at the future accelerator facility FAIR. The goal of the experiment is to study the QCD phase diagram in the vincinity of the QCD critical point. To do so, CBM aims at measuring rare probes among them open charm. In order to identify those rare and short lived particles despite the rich combinatorial background generated in heavy ion collisions, a micro vertex detector (MVD) providing an unprecedented combination of high rate capability and radiation hardness, very light material budget and excellent granularity is required. In this work, we will discuss the concept of this detector and summarize the status of the R&D

Mobilité humaine, droits et protection internationale : répondre à la crise climatique: Human mobility, rights and international protection: responding to the climate crisis

Le HCR examine l'éventail des options de protection juridique internationale dans le contexte des déplacements transfrontaliers déclenchés par les impacts des changements climatiques. Il met également en exergue la nécessité d’étendre les approches visant à trouver des solutions à la mobilité humaine. UNHCR discusses the range of options for international legal protection in the context of cross-border displacement triggered by the impacts of climate change. It also underscores the need for a broader approach to addressing human mobility

La movilidad humana, los derechos y la protección internacional: respuesta a la crisis climática

ACNUR analiza el abanico de opciones para la protección jurídica internacional en el contexto de los desplazamientos transfronterizos provocados por los efectos del cambio climático. También subraya la necesidad de un enfoque más amplio para abordar la movilidad humana

Air pollution attributable postneonatal infant mortality in U.S. metropolitan areas: a risk assessment study

BACKGROUND: The impact of outdoor air pollution on infant mortality has not been quantified. METHODS: Based on exposure-response functions from a U.S. cohort study, we assessed the attributable risk of postneonatal infant mortality in 23 U.S. metropolitan areas related to particulate matter <10 μm in diameter (PM(10)) as a surrogate of total air pollution. RESULTS: The estimated proportion of all cause mortality, sudden infant death syndrome (normal birth weight infants only) and respiratory disease mortality (normal birth weight) attributable to PM(10 )above a chosen reference value of 12.0 μg/m(3 )PM(10 )was 6% (95% confidence interval 3–11%), 16% (95% confidence interval 9–23%) and 24% (95% confidence interval 7–44%), respectively. The expected number of infant deaths per year in the selected areas was 106 (95% confidence interval 53–185), 79 (95% confidence interval 46–111) and 15 (95% confidence interval 5–27), respectively. Approximately 75% of cases were from areas where the current levels are at or below the new U.S. PM(2.5 )standard of 15 μg/m(3 )(equivalent to 25 μg/m(3 )PM(10)). In a country where infant mortality rates and air pollution levels are relatively low, ambient air pollution as measured by particulate matter contributes to a substantial fraction of infant death, especially for those due to sudden infant death syndrome and respiratory disease. Even if all counties would comply to the new PM(2.5 )standard, the majority of the estimated burden would remain. CONCLUSION: Given the inherent limitations of risk assessments, further studies are needed to support and quantify the relationship between infant mortality and air pollution

Transcription-coupled deposition of histone modifications during MHC class II gene activation

Posttranslational histone modifications associated with actively expressed genes are generally believed to be introduced primarily by histone-modifying enzymes that are recruited by transcription factors or their associated co-activators. We have performed a comprehensive spatial and temporal analyses of the histone modifications that are deposited upon activation of the MHC class II gene HLA-DRA by the co-activator CIITA. We find that transcription-associated histone modifications are introduced during two sequential phases. The first phase precedes transcription initiation and is characterized exclusively by a rapid increase in histone H4 acetylation over a large upstream domain. All other modifications examined, including the acetylation and methylation of several residues in histone H3, are restricted to short regions situated at or within the 5′ end of the gene and are established during a second phase that is concomitant with ongoing transcription. This second phase is completely abrogated when elongation by RNA polymerase II is blocked. These results provide strong evidence that transcription elongation can play a decisive role in the deposition of histone modification patterns associated with inducible gene activation

Expression of RAB4B, a protein governing endocytic recycling, is co-regulated with MHC class II genes

The small GTPase RAB4 regulates endocytic recycling, a process that contributes to Major Histocompatibility Complex (MHC)-mediated antigen presentation by specialized antigen presenting cells (APC) of the immune system. The gene encoding the RAB4B isoform of RAB4 was singled out by two complementary genome-wide screens. One of these consisted of a computer scan to identify genes containing characteristic MHC class II-related regulatory sequences. The second was the use of chromatin immunoprecipitation coupled to microarrays (ChIP-on-chip) to identify novel targets of a transcriptional co-activator called the MHC class II transactivator (CIITA). We show that the RAB4B gene is regulated by a typical MHC class II-like enhancer that is controlled directly by both CIITA and the multiprotein transcription factor complex known as the MHC class II enhanceosome. RAB4B expression is thus activated by the same regulatory machinery that is known to be essential for the expression of MHC class II genes. This molecular link between the transcriptional activation of RAB4B and MHC class II genes implies that APC boost their antigen presentation capacity by increasing RAB4-mediated endocytic recycling