An unexpected role for RNA in the recognition of DNA by the innate immune system

A central function of our innate immune system is to sense microbial pathogens through the presence of their nucleic acid genomes or their transcriptional or replicative activity. In mammals, a receptor-based system is mainly responsible for the detection of these "non self" nucleic acids. Tremendous progress has been made in the past years in identifying the host constituents that are required for this intricate task. With regard to the sensing of RNA genome based pathogens by our innate immune system, a picture is emerging that includes certain families of the toll-like receptor family (TLR3, TLR7, TLR8) and the RIG-I like helicases (RIG-I, MDA5 and LGP2). Genetic loss of function studies implicate that the absence of these pathways can lead to a complete lack of recognition of certain RNA viruses. At the same time, intracellular DNA can also trigger potent innate immune responses, yet the players in this field are less clear. We and another group have recently identified a role for RNA polymerase III in the conversion of AT-rich DNA into an RNA ligand that is sensed by the RIG-I pathway. In this review article, we will discuss the mechanisms and implications of this novel pathway

A szél- és napnapenergia, valamint az energetikai célú biomassza hasznosításának éghajlati és társadalmi-gazdasági kérdései a Hernád-völgyben = Climatic conditions and social-economic issues of the utilization of wind, solar and biomass energy in the Hernád-valley, North Hungary

A kutatás során a Hernád-völgy társadalmi-gazdasági és éghajlati adottságait vizsgáltuk azzal a céllal, hogy megállapítsuk: ezek milyen mértékig segítik elő vagy gátolják a szél- és napenergia, valamint a biomassza energetikai célú hasznosítását Statisztikai források alapján feltártuk a Hernád-völgy hátrányos helyzetű településeinek legfontosabb gazdasági-társadalmi adatait, valamint az erdészeti biomasszára vonatkozó adatokat. A megyei, régiós és országos átlagadatokkal összehasonlítva többek között megállapítottuk, hogy a víz-, csatorna- és föld-gázvezetékek kiépítése jóval kedvezőtlenebb. Utóbbi kettő indokolttá teheti az energetikai fejlesztéseket. A kistáj bioenergetikai lehetőségeinél elmondható, hogy az erdészeti faapríték potenciálja feltétlenül figyelembe veendő. Statisztikai adatfeldolgozás és a térinformatikai módszerek egybekapcsolásával elvégzett vizsgálataink azt mutatják, hogy a nagy időbeli fluktuáció ellenére hatékony lehet a terület szélenergiájának felhasználása, elsősorban az alacsony indítási sebességű szélerőművek vagy a szélerőgépek esetében. A Hernád-völgy napenergia potenciáljának feltárásához a fenti két módszerrel elvégeztük a térségbe jutó, a helyi, elsősorban a domborzati körülmények által jelentősen befolyásolt globálsugárzás időbeli és térbeli eloszlásának elemzését. A felszínre érkező globálsugárzási adatok kiértékelése elengedhetetlen információkat nyújt a Hernád-völgyben tervezett napenergia beruházások tervezésénél, gazdasági elemzésénél. | Role of socio-economic and climatic endowments of the Hernád-valley in energetic solar, wind and biomass utilization have been examined in our research program. Most important socio-economic characteristics of settlements and parameters of biomass production in the Hernád-valley have been determined on the base of statistical data. Compared to county, region, or national averages water, gas and drainage systems are rather underdeveloped in the Hernád-valley. These facts support renewable energetic developments. The micro region has a good potential in chopped wood biomass. Despite its strong temporal fluctuations wind energy utilization can be effective especially in the case of low critical velocity wind turbines and windmills according to our results gained using statistical data analyses combined with geoinformatic methods. However, small windmills and wind generators with capacities of several hundred watts or kilowatts could be more effective solutions, since they can be operated in island mode, what means that their establishment requires much less permissions. The before mentioned two methods have been used for examination of solar energy potential of the Hernád-valley as well. Spatial and temporal patterns of solar irradiance strongly influenced by the relief have been determined. Amount of solar irradiance can be measured on the surface provides important information for the planning and economic analyses of solar energy utilization projects in the Hernád-valley

An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility

The voltage-gated Kv1.3 K(+) channel plays a key role in the activation of T lymphocytes. Kv1.3 blockers selectively suppress immune responses mediated by effector memory T cells, which indicates the great potential of selective Kv1.3 inhibitors in the therapy of certain autoimmune diseases. Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin is a high affinity blocker of Kv1.3, but also blocks Kv1.2 with similar potency. We designed and produced three AnTx variants: ([F32T]-AnTx, [N17A]-AnTx, [N17A/F32T]-AnTx) using solid-phase synthesis with the goal of improving the selectivity of the toxin for Kv1.3 over Kv1.2 while keeping the high affinity for Kv1.3. We used the patch-clamp technique to determine the blocking potency of the synthetic toxins on hKv1.3, mKv1.1, hKv1.2 and hKCa3.1 channels. Of the three variants [N17A/F32T]-AnTx maintained the high affinity of the natural peptide for Kv1.3 but became more than 16000-fold selective over Kv1.2. NMR data and molecular dynamics simulations suggest that the more rigid structure with restricted conformational space of the double substituted toxin compared to the flexible wild-type one is an important determinant of toxin selectivity. Our results provide the foundation for the possibility of the production and future therapeutic application of additional, even more selective toxins targeting various ion channels

Measurement of vector boson scattering and constraints on anomalous quartic couplings from events with four leptons and two jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for dijet resonances in proton-proton collisions at root s=13 TeV and constraints on dark matter and other models

Correction: DOI:10.1016/j.physletb.2017.09.029Peer reviewe

Search for new physics with dijet angular distributions in proton-proton collisions at root S = 13 TeV

Peer reviewe