Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

The steroid-hormone ecdysone coordinates parallel pupariation neuromotor and morphogenetic subprograms via epidermis-to-neuron Dilp8-Lgr3 signal induction

Funding Information: We thank Drs. Carlos Ribeiro, Christen Mirth, Elio Sucena, Filip Port, Frank Schnorrer, Julien Colombani, Maria Dominguez, Maria Luisa Vasconcelos, Pierre Leopold, Simon Bullock, Rita Teodoro, Gerald Rubin, Melissa Harrison, Kate O’Connor-Giles, Jill Wildonger, Mariana Melani, Pablo Wappner, and Christian Wegener for fly stocks and reagents. We thank Ryohei Yagi and Konrad Basler for the LHV2 plasmid and Brain McCabe for the mhc-Gateway destination plasmid. We thank Carlos Ribeiro and Dennis Goldschmidt for help in designing and constructing one of the pupariation arenas and Mariana Melani, Pablo Wappner, Arash Bashirullah, and Filip Port for sharing resources and unpublished data. We thank Arash Bashirullah, Fillip Port, and Carlos Ribeiro for discussions and/or comments on the manuscript, and Jim Truman for discussions on Fraenkel’s pupariation factors. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. Work in the Integrative Biomedicine Laboratory was supported by the European Commission FP7 (PCIG13-GA-2013-618847), by the FCT (IF/00022/2012; Congento LISBOA-01-0145-FEDER-022170, cofinanced by FCT/Lisboa2020; UID/Multi/04462/2019; PTDC/BEXBCM/1370/2014; PTDC/MED-NEU/30753/2017; PTDC/BIA-BID/31071/2017; FCT SFRH/BPD/94112/ 2013; SFRH/BD/94931/2013), the MIT Portugal Program (MIT-EXPL/BIO/0097/2017), and FAPESP (16/09659-3, 16/10342-4, and 17/17904-0). AG is a CONICET researcher, YV holds a CONICET postdoctoral fellowship and FPS and MJD hold a PhD fellowship from CONICET. Work in the Garelli lab was supported by ANPCyT (Agencia Nacional para la Promoción de la Ciencia y la Tecnología, PICT 2014-2900 and PICT 2017-0254) and CONICET (PIP11220150100182CO). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Innate behaviors consist of a succession of genetically-hardwired motor and physiological subprograms that can be coupled to drastic morphogenetic changes. How these integrative responses are orchestrated is not completely understood. Here, we provide insight into these mechanisms by studying pupariation, a multi-step innate behavior of Drosophila larvae that is critical for survival during metamorphosis. We find that the steroid-hormone ecdysone triggers parallel pupariation neuromotor and morphogenetic subprograms, which include the induction of the relaxin-peptide hormone, Dilp8, in the epidermis. Dilp8 acts on six Lgr3-positive thoracic interneurons to couple both subprograms in time and to instruct neuromotor subprogram switching during behavior. Our work reveals that interorgan feedback gates progression between subunits of an innate behavior and points to an ancestral neuromodulatory function of relaxin signaling.publishersversionpublishe

The P2Y4 receptor forms homo-oligomeric complexes in several CNS and PNS neuronal cells

It is well established that several cell surface receptors interact with each other to form dimers and oligomers, which are essential for their activation. Since little is known about the quaternary structure of P2Y receptors, in the present work, we investigated the expression of the G-protein-coupled P2Y4 subunit as monomeric or higher-order complex protein. We examined both endogenously expressed P2Y4 subtype with the aid of specific anti-P2Y4 antiserum, and heterologously transfected P2Y4-tagged receptors with the use of antitag antibodies. In both cases, we found the P2Y4 receptor displaying molecular masses corresponding to monomeric, dimeric and oligomeric structures. Experiments performed in the absence of reducing agents demonstrated that there is a strict correlation among the multiple protein bands and that the multimeric forms are at least partially assembled by disulphide bonds. The direct demonstration of P2Y4 homodimerisation comes instead from co–transfection and differential co–immunoprecipitation experiments, with the use of differently tagged P2Y4 receptors and antitag antibodies. The structural propensity of the P2Y4 protein to form homo-oligomers may open the possibility of a novel regulatory mechanism of physiopathological functions for this and additional P2Y receptors

Interaction of convective organisation with monsoon precipitation, atmosphere, surface and sea: the 2016 INCOMPASS field campaign in India

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary‐layer and convective‐cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe‐146 aircraft for the first project of this scale in India, to accrue almost 100 h of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary‐layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre‐monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4 km convection‐permitting limited‐area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy‐covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid‐level dry intrusion during the monsoon onset

Interaction of convective organisation with monsoon precipitation, atmosphere, surface and sea: the 2016 INCOMPASS field campaign in India

The INCOMPASS field campaign combines airborne and ground measurements of the 2016 Indian monsoon, towards the ultimate goal of better predicting monsoon rainfall. The monsoon supplies the majority of water in South Asia, but forecasting from days to the season ahead is limited by large, rapidly developing errors in model parametrizations. The lack of detailed observations prevents thorough understanding of the monsoon circulation and its interaction with the land surface: a process governed by boundary-layer and convective-cloud dynamics. INCOMPASS used the UK Facility for Airborne Atmospheric Measurements (FAAM) BAe-146 aircraft for the first project of this scale in India, to accrue almost 100 hours of observations in June and July 2016. Flights from Lucknow in the northern plains sampled the dramatic contrast in surface and boundary layer structures between dry desert air in the west and the humid environment over the northern Bay of Bengal. These flights were repeated in pre-monsoon and monsoon conditions. Flights from a second base at Bengaluru in southern India measured atmospheric contrasts from the Arabian Sea, over the Western Ghats mountains, to the rain shadow of southeast India and the south Bay of Bengal. Flight planning was aided by forecasts from bespoke 4km convection-permitting limited-area models at the Met Office and India's NCMRWF. On the ground, INCOMPASS installed eddy-covariance flux towers on a range of surface types, to provide detailed measurements of surface fluxes and their modulation by diurnal and seasonal cycles. These data will be used to better quantify the impacts of the atmosphere on the land surface, and vice versa. INCOMPASS also installed ground instrumentation supersites at Kanpur and Bhubaneswar. Here we motivate and describe the INCOMPASS field campaign. We use examples from two flights to illustrate contrasts in atmospheric structure, in particular the retreating mid-level dry intrusion during the monsoon onset

Director Characteristics and Firm Performance

The traditional methodology examining optimal boards relates a simple board variable (e.g. independence or board demography) to firm performance, however, ig- noring other board characteristics. This paper investigates how the education and business experience of directors affect firm performance. The sample consists of 1,574 directorships from 224 listed firms in Switzerland. Using OLS and including control variables, the results show that graduates of minor Swiss universities are negatively related to Tobin’s Q, and industrial knowledge and Tobin’s Q are nega- tively correlated if the firm has more divisions. In addition, director fixed effects (or unobserved characteristics) are significant, but improve the explanatory power of the models only by 5 percent