Gene organization, evolution and expression of the microtubule-associated protein ASAP (MAP9)

International audienceBackground : ASAP is a newly characterized microtubule-associated protein (MAP) essential for propercell-cycling. We have previously shown that expression deregulation of human ASAP results in profounddefects in mitotic spindle formation and mitotic progression leading to aneuploidy, cytokinesis defects and/or cell death. In the present work we analyze the structure and evolution of the ASAP gene, as well as thedomain composition of the encoded protein. Mouse and Xenopus cDNAs were cloned, the tissueexpression characterized and the overexpression profile analyzed. Results : Bona fide ASAP orthologs are found in vertebrates with more distantly related potentialorthologs in invertebrates. This single-copy gene is conserved in mammals where it maps to syntenicchromosomal regions, but is also clearly identified in bird, fish and frog. The human gene is stronglyexpressed in brain and testis as a 2.6 Kb transcript encoding a ~110 KDa protein. The protein containsMAP, MIT-like and THY domains in the C-terminal part indicative of microtubule interaction, while the N-terminal part is more divergent. ASAP is composed of ~42% alpha helical structures, and two main coiled-coil regions have been identified. Different sequence features may suggest a role in DNA damage response. As with human ASAP, the mouse and Xenopus proteins localize to the microtubule network in interphaseand to the mitotic spindle during mitosis. Overexpression of the mouse protein induces mitotic defectssimilar to those observed in human. In situ hybridization in testis localized ASAP to the germ cells, whereasin culture neurons ASAP localized to the cell body and growing neurites. Conclusion : The conservation of ASAP indicated in our results reflects an essential function invertebrates. We have cloned the ASAP orthologs in mouse and Xenopus, two valuable models to studythe function of ASAP. Tissue expression of ASAP revealed a high expression in brain and testis, two tissuesrich in microtubules. ASAP associates to the mitotic spindle and cytoplasmic microtubules, and representsa key factor of mitosis with possible involvement in other cell cycle processes. It may have a role inspermatogenesis and also represents a potential new target for antitumoral drugs. Possible involvement inneuron dynamics also highlights ASAP as a candidate target in neurodegenerative disease

Assessment of isoprene and near-surface ozone sensitivities to water stress over the Euro-Mediterranean region

Plants emit biogenic volatile organic compounds (BVOCs) in response to changes in environmental conditions (e.g. temperature, radiation, soil moisture). In the large family of BVOCs, isoprene is by far the strongest emitted compound and plays an important role in ozone chemistry, thus affecting both air quality and climate. In turn, climate change may alter isoprene emissions by increasing temperature as well as the occurrence and intensity of severe water stresses that alter plant functioning. The Model of Emissions of Gases and Aerosols from Nature (MEGAN) provides different parameterizations to account for the impact of water stress on isoprene emissions, which essentially reduces emissions in response to the effect of soil moisture deficit on plant productivity. By applying the regional climate–chemistry model RegCM4chem coupled to the Community Land Model CLM4.5 and MEGAN2.1, we thus performed sensitivity simulations to assess the effects of water stress on isoprene emissions and near-surface ozone levels over the Euro-Mediterranean region and across the drier and wetter summers over the 1992–2016 period using two different parameterizations of the impact of water stress implemented in the MEGAN model. Over the Euro-Mediterranean region and across the simulated summers, water stress reduces isoprene emissions on average by nearly 6 %. However, during the warmest and driest selected summers (e.g. 2003, 2010, 2015) and over large isoprene-source areas (e.g. the Balkans), decreases in isoprene emissions range from −20 % to −60 % and co-occur with negative anomalies in precipitation, soil moisture and plant productivity. Sustained decreases in isoprene emissions also occur after prolonged or repeated dry anomalies, as observed for the summers of 2010 and 2012. Although the decrease in isoprene emissions due to water stress may be important, it only reduces near-surface ozone levels by a few percent due to a dominant VOC-limited regime over southern Europe and the Mediterranean Basin. Overall, over the selected analysis region, compared to the old MEGAN parameterization, the new one leads to localized and 25 %–50 % smaller decreases in isoprene emissions and 3 %–8 % smaller reductions in near-surface ozone levels.</p

Changes in the global hospitalisation burden of respiratory syncytial virus in young children during the COVID-19 pandemic: a systematic analysis

Background The coronavirus disease 2019 (COVID-19) pandemic was reported to have impacted RSV epidemiology and could have important implications for RSV prevention and control strategies. We aimed to understand the RSV-associated acute lower respiratory infection (ALRI) hospitalisation burden in children younger than five years during the COVID-19 pandemic period and the possible changes in RSV epidemiology from a global perspective.Methods We conducted a systematic literature search for studies published between January 1, 2020 and June 30, 2022, from MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Web of Science, WHO COVID-19 database, CINAHL, LILACS, OpenGrey, CNKI, WanFang and ChongqingVIP. We included unpublished RSV epidemiology data shared by international collaborators. Eligible studies reported data for RSV-associated ALRI hospital admission rates or at least one of the following severity measures: the proportion of RSV cases that needed supplemental oxygen, mechanical ventilation or intensive care unit admission, and in-hospital case fatality ratio. A generalised linear mixed-effects model was used for data synthesis to understand the changes in the incidence, age distribution and severity of RSV-associated ALRI hospitalisations in children under five years during the COVID-19 pandemic, compared to the year 2019. Findings We included 61 studies, 14 studies from published literature and 47 unpublished datasets. Most studies (51/61) were from the high-income region, followed by the upper-middle-income region (9/61); only one study was from the lower-middle-income region, and no studies were from the low-income region. Compared to 2019, all income regions saw substantial decreases in RSV-associated ALRI hospitalisation rate across all age groups in 2020; the number of RSV-associated ALRI hospitalisations in children aged 0–&lt;60 months decreased by approximately 80% (325,000 to 66,000), 14% (581,000 to 501,000) and 42% (1,378,000 to 795,000) for high-income, upper-middle-income and lower-middle-income countries, respectively. RSV hospitalisation rate started to rise in 2021, and by March 2022, the annualised rate returned to a level comparable to 2019 (6·0/1000, 95% uncertainty interval [UI] 5·4–6·8 by March 2022 vs 5·0/1000, 3·6–6·8 in 2019) in high-income countries while remaining lower in middle-income countries. Across all time periods and income regions, RSV-associated ALRI hospitalisation rates peaked in infants aged 0–&lt;3 months and declined with increasing age. Compared to the pre-pandemic period, there was a significantly increased proportion of RSV-associated ALRI hospitalisations in those aged 12–&lt;24 months in high-income and upper-middle-income regions (ORs ranged from 1·30 [1·07–1·59] to 2·05 [1·66–2·54]). No consistent changes in disease severity were observed. Interpretation Our study documented a significant reduction in RSV-associated ALRI hospitalisation burden in children under five years during the first year of the COVID-19 pandemic. A rebound to pre-pandemic levels in RSV-associated ALRI hospitalisation rate was observed in the high-income region by March 2022 but not in the middle-income region, suggesting a more persistent negative impact of the COVID-19 pandemic on health-care systems and health-care access in middle-income regions. RSV surveillance needs to be established (or re-established) to monitor the changes in RSV epidemiology, particularly in low- and lower-middle-income countries.Funding EU Innovative Medicines Initiative Preparing for RSV Immunisation and Surveillance in Europe (PROMISE); Bill &amp; Melinda Gates Foundation; World Health Organization. <br/

Relationship between Regulatory T Cells and Immune Activation in Human Immunodeficiency Virus-Infected Patients Interrupting Antiretroviral Therapy

Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r = −0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p = 0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p = 0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI

Particulate matter exposure during pregnancy is associated with birth weight, but not gestational age, 1962-1992: a cohort study

<p>Abstract</p> <p>Background</p> <p>Exposure to air pollutants is suggested to adversely affect fetal growth, but the evidence remains inconsistent in relation to specific outcomes and exposure windows.</p> <p>Methods</p> <p>Using birth records from the two major maternity hospitals in Newcastle upon Tyne in northern England between 1961 and 1992, we constructed a database of all births to mothers resident within the city. Weekly black smoke exposure levels from routine data recorded at 20 air pollution monitoring stations were obtained and individual exposures were estimated via a two-stage modeling strategy, incorporating temporally and spatially varying covariates. Regression analyses, including 88,679 births, assessed potential associations between exposure to black smoke and birth weight, gestational age and birth weight standardized for gestational age and sex.</p> <p>Results</p> <p>Significant associations were seen between black smoke and both standardized and unstandardized birth weight, but not for gestational age when adjusted for potential confounders. Not all associations were linear. For an increase in whole pregnancy black smoke exposure, from the 1^st(7.4 μg/m³) to the 25^th(17.2 μg/m³), 50^th(33.8 μg/m³), 75^th(108.3 μg/m³), and 90^th(180.8 μg/m³) percentiles, the adjusted estimated decreases in birth weight were 33 g (SE 1.05), 62 g (1.63), 98 g (2.26) and 109 g (2.44) respectively. A significant interaction was observed between socio-economic deprivation and black smoke on both standardized and unstandardized birth weight with increasing effects of black smoke in reducing birth weight seen with increasing socio-economic disadvantage.</p> <p>Conclusions</p> <p>The findings of this study progress the hypothesis that the association between black smoke and birth weight may be mediated through intrauterine growth restriction. The associations between black smoke and birth weight were of the same order of magnitude as those reported for passive smoking. These findings add to the growing evidence of the harmful effects of air pollution on birth outcomes.</p

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)