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Innate immunity is the first line of host defense against viral infection. After invading into the cells, pathogen-associated-molecular-patterns derived from viruses are recognized by pattern recognition receptors to activate the downstream signaling pathways to induce the production of type I interferons (IFN-I) and inflammatory cytokines, which play critical functions in the host antiviral innate immune responses. Guanylate-binding proteins (GBPs) are IFN-inducible antiviral effectors belonging to the guanosine triphosphatases family. In addition to exerting direct antiviral functions against certain viruses, a few GBPs also exhibit regulatory roles on the host antiviral innate immunity. However, our understanding of the underlying molecular mechanisms of GBPs' roles in viral infection and host antiviral innate immune signaling is still very limited. Therefore, here we present an updated overview of the functions of GBPs during viral infection and in antiviral innate immunity, and highlight discrepancies in reported findings and current challenges for future studies, which will advance our understanding of the functions of GBPs and provide a scientific and theoretical basis for the regulation of antiviral innate immunity.

Human guanylate-binding protein 1 (hGBP1) is a key player in innate immunity and fights diverse intracellular microbial pathogens. Its antimicrobial functions depend on hGBP1’s GTP binding- and hydrolysis-induced abilities to form large, structured polymers and to attach to lipid membranes. Crucial for both of these biochemical features is the nucleotide-controlled release of the C terminally located farnesyl moiety. Here, we address molecular details of the hGBP1 membrane binding mechanism by employing recombinant, fluorescently labeled hGBP1, and artificial membranes. We demonstrate the importance of the GTPase activity and the resulting structural rearrangement of the hGBP1 molecule, which we term the open state. This open state is supported and stabilized by homodimer contacts involving the middle domain of the protein and is further stabilized by binding to the lipid bilayer surface. We show that on the surface of the lipid bilayer a hGBP1 monolayer is built in a pins in a pincushion-like arrangement with the farnesyl tail integrated in the membrane and the N-terminal GTPase domain facing outwards. We suggest that similar intramolecular contacts between neighboring hGBP1 molecules are responsible for both polymer formation and monolayer formation on lipid membranes. Finally, we show that tethering of large unilamellar vesicles occurs after the vesicle surface is fully covered by the monolayer. Both hGBP1 polymer formation and hGBP1-induced vesicle tethering have implications for understanding the molecular mechanism of combating bacterial pathogens. Databases: Structural data are available in RCSB Protein Data Bank under the accession numbers: 6K1Z, 2D4H.

Modern European beekeeping is facing numerous challenges due to a variety of factors, mainly related to globalisation, agrochemical pollution and environmental changes. In addition to this, new pathogens threaten the health of European honey bees. In that context, correct colony management should encompass a wider vision, where productivity aspects are linked to a One Health approach in order to protect honey bees, humans and the environment. This paper describes a novel tool to be applied in beekeeping operations: good beekeeping practices (GBPs). The authors ranked a list of GBPs scored against their importance and validated by an international team, including researchers, national animal health authorities and international beekeepers' associations. These activities were carried out in the project 'BPRACTICES', approved within the transnational call of the European Research Area Network on Sustainable Animal Production (ERA-NET SusAn) in the Horizon 2020 Research and Innovation Programme of the European Union. This study, created through an international collaboration, aims to present an innovative and implementable approach, similar to applications already adopted in other livestock production systems.L’apiculture moderne européenne est confrontée à de nombreuses difficultés dues à divers facteurs, pour la plupart liés à la mondialisation, à la pollution agrochimique et à la modification de l’environnement. À ces facteurs s’ajoute l’émergence de nouveaux agents pathogènes qui menacent la santé des abeilles mellifères d’Europe. Dans ce contexte, une gestion appropriée des colonies d’abeilles devrait reposer sur une vision plus large, dans laquelle les aspects relevant de la productivité sont examinés suivant une approche « Une seule santé » afin de protéger les abeilles mellifères, les humains et l’environnement. Les auteurs décrivent un nouvel outil destiné à l’apiculture : les bonnes pratiques apicoles. Ils ont évalué et classé par ordre d’importance une liste de bonnes pratiques apicoles validées par une équipe internationale composée de chercheurs, d’autorités nationales de la santé animale et d’associations internationales d’apiculteurs. Ces activités ont été conduites dans le cadre du projet « BPRACTICES », proposition retenue suite à l’appel à projets transnationaux du réseau ERA–NET SusAn (European Research Area Network on Sustainable Animal Production) au sein du Programme Horizon 2020 de l’Union européenne pour la recherche et l’innovation. Conçue sous forme de collaboration internationale, cette étude vise à proposer une approche innovante et pratique, similaire aux applications précédemment adoptées dans d’autres systèmes de production animale.La apicultura europea hace frente a numerosos problemas resultantes de diversos factores, relacionados principalmente con la mundialización, la contaminación agroquímica y los cambios ambientales, a todo lo cual se suman nuevos patógenos que amenazan la salud de las abejas melíferas europeas. En este contexto, una correcta gestión de las colonias debe traer aparejada una visión más global, en la que las cuestiones de productividad se consideren en clave de «Una sola salud» con objeto de proteger tanto a las abejas melíferas como a las personas y el medio ambiente. En este artículo se describe una novedosa herramienta aplicable a la actividad apícola: las buenas prácticas de apicultura. Los autores jerarquizaron una serie de buenas prácticas de apicultura seleccionadas, validadas y puntuadas según su importancia por un equipo internacional que incluía a investigadores, autoridades nacionales de sanidad animal y asociaciones internacionales de apicultores. Este trabajo formaba parte del proyecto «BPRACTICES», aprobado con ocasión de la convocatoria internacional abierta por la Red del espacio europeo de investigación en sanidad animal sostenible (ERA–NET SusAn), inscrita a su vez en Horizonte 2020, el programa de investigación e innovación de la Unión Europea. El estudio aquí descrito, fruto de la colaboración internacional, tiene por objeto presentar un planteamiento novedoso y viable, parecido a las aplicaciones ya implantadas en otros sistemas de producción animal.

Planet is a vertically integrated aerospace and data analytics company that operates the world's largest commercial fleet of remote sensing satellites. Our mission is to image the whole world everyday, and make change visible, accessible, and actionable. We have launched over 350 satellites and built up an automated mission control and ground station infrastructure to monitor and control the satellites, and download the imagery data. Historically, small satellite radios have been downlink limited because of tight size, weight, and power (SWaP) constraints. Rapid prototyping, iteration, and adaptation of the latest commercial-o_-the-shelf (COTS) technology has allowed for continuous improvements in data throughput on our high speed radio from a very low-cost cubesat platform. In this talk, we will report on our latest X-band radio and antenna solution which has achieved a data rate over 1.6 Gbps from a 3U CubeSat on-orbit. Planet's High Speed Downlink 2 (HSD2) is the latest generation compact, low-mass, and low-power radio that was built and deployed on 3U form-factor imaging CubeSats in December 2018. This system operates at X- band and is built using COTS parts with a dual polarization antenna. The two physical channels represent the two polarization modes, right hand circular polarization (RHCP) and left hand circular polarization (LHCP) and each physical channel utilizes 300 MHz of total bandwidth. Within each physical channel, there are three logical channels spaced 100 MHz apart center-to-center frequency. The individual channel symbol rate is 76.8 Msps. Each physical channel has 1 W RF output power and 15 dBi antenna gain. The total DC power consumption of the radio including the processor and the FPGA is 50Wand the total volume occupied by the radio and antenna, including the mechanical deployment structure for the antenna is 0.25U. The commercial digital television broadcasting standard DVB-S2 is used for modulation and coding. An adaptive coding and modulation (ACM) scheme is used to dynamically change the modulation and coding for each channel individually based on the available link margin. Our ground station network includes 15 dishes (29 dB/K gain-to-noise-temperature) across 5 sites located around the world. The HSD2 is capable of providing downlink volume of over 80 GB during a single ground station pass.

6 Abstract Leishmaniasis is a neglected tropical disease, which belongs to the top health problems because it is endemic in 98 countries in Asia, Africa, the Americas and the Mediterranean region, and is gradually expanding to new areas, including Central Europe and USA. Clinical manifestations of leishmaniasis include a diverse range of forms, ranging from non-lethal cutaneous leishmaniasis to potentially lethal visceral leishmaniasis. Asymptomatic cases are known to exist in endemic areas. Different species of Leishmania induce distinct symptoms, but even the patients infected by the same species develop different symptoms and may respond differently to the treatment. Thus, one of the challenges is to explain the observed variability of leishmaniasis that cannot be attributed to the currently known factors. To find novel regulatory factors of the disease we tested molecules that were shown to play role in other infections and mapped loci controlling parasite load after L. major infection. We also determined genetic control of survival after infection with tick-borne encephalitis virus (TBEV) in order to establish whether there are common elements in response to L. major and TBEV. Interferon-induced GTPases (guanylate-binding proteins, GBPs) play an important role in inflammasome activation and mediate...

Modern European beekeeping is facing numerous challenges due to a variety of factors, mainly related to globalisation, agrochemical pollution and environmental changes. In addition to this, new pathogens threaten the health of European honey bees. In that context, correct colony management should encompass a wider vision, where productivity aspects are linked to a One Health approach in order to protect honey bees, humans and the environment. This paper describes a novel tool to be applied in beekeeping operations: good beekeeping practices (GBPs). The authors ranked a list of GBPs scored against their importance and validated by an international team, including researchers, national animal health authorities and international beekeepers' associations. These activities were carried out in the project 'BPRACTICES', approved within the transnational call of the European Research Area Network on Sustainable Animal Production (ERA-NET SusAn) in the Horizon 2020 Research and Innovation Programme of the European Union. This study, created through an international collaboration, aims to present an innovative and implementable approach, similar to applications already adopted in other livestock production systems. European UnionEuropean Commission [696231, 83] This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 696231 [SusAn] ID 83.

Summary: Guanylate-binding protein (GBP) 5 is an interferon (IFN)-inducible cellular factor reducing HIV-1 infectivity by an incompletely understood mechanism. Here, we show that this activity is shared by GBP2, but not by other members of the human GBP family. GBP2/5 decrease the activity of the cellular proprotein convertase furin, which mediates conversion of the HIV-1 envelope protein (Env) precursor gp160 into mature gp120 and gp41. Because this process primes HIV-1 Env for membrane fusion, viral particles produced in the presence of GBP2/5 are poorly infectious due to increased incorporation of non-functional gp160. Furin activity is critical for the processing of envelope glycoproteins of many viral pathogens. Consistently, GBP2/5 also inhibit Zika, measles, and influenza A virus replication and decrease infectivity of viral particles carrying glycoproteins of Marburg and murine leukemia viruses. Collectively, our results show that GPB2/5 exert broad antiviral activity by suppressing the activity of the virus-dependency factor furin. : The cellular protease furin processes numerous substrates, including the envelope proteins of many viral pathogens. Here, Braun et al. show that guanylate-binding proteins 2 and 5 are interferon-inducible restriction factors that reduce virion infectivity by inhibiting furin activity and consequently maturation of viral envelope glycoproteins. Keywords: GBPs, restriction factor, furin, HIV, influenza A virus, measles virus, Zika virus, viral envelope proteins

With the CMOS process technology progress, transistor can achieve up to 260 GHz ft and fmax referenced to the top metal, it makes possible to develop lower cost circuits and blocks for THz high speed implementations such as active imagine system, short distance chip to chip communication systems and large scale high speed ultra low power switch networks. The dissertation shows an 8x1 phased array transmitter working at 370-410 GHz with peak EIRP of 8.5 dBm, a QPSK modulated 20 Gbit/s transceiver front end (including modulator, voltage control oscillator, power splitter, doubler, mixer and wide-band baseband amplifier.) at 155 GHz and two cross connected high peed ultra low power switch matrices (an 8x8 matrix up to 25 Gbit/s matrix and a 16x16 matrix built using four 8x8 matrix). All circuits and blocks are built using the Global Foundries 45 nm CMOS SOI (silicon on isotropic) process.

International audience; The cytoskeleton occupies a central role in cellular immunity by promoting bacterial sensing and antibacterial functions. Septins are cytoskeletal proteins implicated in various cellular processes, including cell division. Septins also assemble into cage-like structures that entrap cytosolic Shigella, yet how septins recognize bacteria is poorly understood. Here, we discover that septins are recruited to regions of micron-scale membrane curvature upon invasion and division by a variety of bacterial species. Cardiolipin, a curvature-specific phospholipid, promotes septin recruitment to highly curved membranes of Shigella, and bacterial mutants lacking cardiolipin exhibit less septin cage entrapment. Chemically inhibiting cell separation to prolong membrane curvature or reducing Shigella cell growth respectively increases and decreases septin cage formation. Once formed, septin cages inhibit Shigella cell division upon recruitment of autophagic and lysosomal machinery. Thus, recognition of dividing bacterial cells by the septin cytoskeleton is a powerful mechanism to restrict the proliferation of intracellular bacterial pathogens.

International audience; Developing organisms use fine-tuning mechanisms to adjust body growth to ever-changing nutritional conditions. In Drosophila, the secretory activity of insulin-producing cells (IPCs) is central to couple systemic growth with amino acids availability. Here, we identify a subpopulation of inhibitory neurons contacting the IPCs (IPC-connecting neurons or ICNs) that play a key role in this coupling. We show that ICNs respond to growth-blocking peptides (GBPs), a family of fat-body-derived signals produced upon availability of dietary amino acids. We demonstrate that GBPs are atypical ligands for the fly EGF receptor (EGFR). Upon activation of EGFR by adipose GBPs, ICN-mediated inhibition of IPC function is relieved, allowing insulin secretion. Our study reveals an unexpected role for EGF-like metabolic hormones and EGFR signaling as critical modulators of neural activity, coupling insulin secretion to the nutritional status.

Integration density, channel scalability, low switching energy and low insertion loss are the major prerequisites for on-chip WDM systems. A number of device geometries have already been demonstrated that fulfill these criteria, at least in part, but combining all of the requirements is still a difficult challenge. Here, we propose and demonstrate a novel architecture consisting of an array of photonic crystal modulators connected by a dielectric bus waveguide. The device architecture features very high scalability and the modulators operate with an AC energy consumption of less than 1fJ/bit. Furthermore, we demonstrate cascadeability and multichannel operation by using a comb laser as the source that simultaneously drives 5 channels. Publisher PDF