Isolation and characterization of novel plekhm1 and def8 mutant alleles in Drosophila

Lysosomal degradation of cytoplasmic components by autophagy ensures the continuous turnover of proteins and organelles and aids cellular survival during nutrient deprivation and other stress conditions. Lysosomal targeting of cytoplasmic proteins and organelles requires the concerted action of several proteins and multisubunit complexes. The core components of this machinery are conserved from yeast to humans and many of them are well-characterized; however, novel molecular players have been recently discovered and are waiting for detailed analysis. The osteopetrosis-linked PLEKHM1 protein is a lysosomal adaptor involved in autophagosome and endosome to lysosome fusion events and its role in lysosomal positioning in osteoclasts was reported together with its proposed binding partner, the relatively uncharacterized DEF8 protein. Here, we report the generation and subsequent analysis of novel mutant alleles of Drosophila plekhm1 and def8. Interestingly, the CRISPR-generated null mutations of these genes do not have any obvious effects on autophagy in Drosophila tissues, even though RNAi knockdown of these genes seems to perturb autophagy. Although these results are quite surprising and raise the possibility of compensatory changes in the case of null mutants, the new alleles will be valuable tools in future studies to understand the cellular functions of Drosophila Plekhm1 and Def8 proteins

Adatszerkezet a kognitív szemantikai elméletekben = Data structure in cognitive semantic theories

A kutatás metaelméleti célkitűzésének megfelelően sikeresen továbbfejlesztettük és a kognitív szemantikára alkalmaztuk a plauzibilis érvelés p-modelljét, mely új megvilágításba helyezte a kognitív szemantika adatfogalmát. Ily módon teljesült az a célkitűzés, hogy eredeti megoldást nyújtsunk a kutatási tervben felvetett problémákra. Ezen célkitűzés elérésében – a kutatási tervnek megfelelően – jelentős szerep jutott az elvégzett nagy számú esettanulmánynak. Az esettanulmányok kétfajta eredménnyel jártak. Egyrészt alátámasztották a p-modell működőképességét és a kognitív szemantika adatkezelésére való alkalmazhatóságát. Többek között tisztázták a fogalmi metaforaelmélet cirkularitásának kérdését, kimutatták, hogy a kognitív metaforakutatásban alkalmazott kísérletek plauzibilis érvelési folyamatokként rekonstruálhatók, és feltárták a kognitív szemantikában gyakran alkalmazott gondolatkísérletek szerkezetét. Másfelől az esettanulmányok eredményei olyan kérdéseket is felvetettek, amelyek kijelölik a kutatások folytatásának irányát. | In accordance with the aim of the project, we applied the p-model of plausible argumentation to cognitive semantics which shed new light on the nature of data in cognitive linguistics. Therefore, the project suggested novel solutions to the problems raised in the proposal. In meeting this requirement – in accordance with the proposal – a great number of case studies played a significant role. The case studies yielded two kinds of results. First, they supported the workability of the p-model and its applicability to data processing in cognitive semantics. Among others, they clarified the issue of the circularity of the conceptual metaphor theory; they showed that experiments in cognitive metaphor research can be reconstructed as processes of plausible argumentation; and they revealed the structure of thought experiments frequently applied in cognitive semantics. Second, the results of the case studies also raised questions which pave the way for the continuation of the research

Citokinellenes terápia az új típusú koronavírus okozta megbetegedés (COVID–19) kezelésében – tocilizumab elsőként való alkalmazása egy hazai infektológiai osztályon (A COVID–19-pandémia orvosszakmai kérdései)

During the past few months, a pandemic originating from China named new coronavirus disease (COVID-19) has shown how vulnerable the world is. To date, no medication supported by randomized clinical trials has been approved for the treatment of COVID-19. At the time of writing of this paper, severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2) has been responsible - according to modest estimations - for around 4 million of infections and 300 000 deaths. Unveiling details of patomechanism, in fatal cases the role of immune dysregulation, namely cytokine release syndrome (CRS) has been discovered. Based on the current knowledge, interleukin-6 (IL6) plays a pivotal role in COVID-19 associated CRS. Case reports and result of small case series suggest efficacy of an IL6 inhibitor monoclonal antibody (tocilizumab) in treating CRS. Authors describe a case and review recent knowledge on the treatment of COVID-19. To our knowledge, the first case of severe COVID-19-associated cytokine storm syndrome - treated succesfully with IL6 monoclocal antibody at a Hungarian department of infectology - is presented here. Orv Hetil. 2020; 161(26): 1070-1077

Oxytocin receptor gene polymorphisms are associated with human directed social behavior in dogs (Canis familiaris)

The oxytocin system has a crucial role in human sociality; several results prove that polymorphisms of the oxytocin receptor gene are related to complex social behaviors in humans. Dogs' parallel evolution with humans and their adaptation to the human environment has made them a useful species to model human social interactions. Previous research indicates that dogs are eligible models for behavioral genetic research, as well. Based on these previous findings, our research investigated associations between human directed social behaviors and two newly described (−212AG, 19131AG) and one known (rs8679684) single nucleotide polymorphisms (SNPs) in the regulatory regions (5′ and 3′ UTR) of the oxytocin receptor gene in German Shepherd (N = 104) and Border Collie (N = 103) dogs. Dogs' behavior traits have been estimated in a newly developed test series consisting of five episodes: Greeting by a stranger, Separation from the owner, Problem solving, Threatening approach, Hiding of the owner. Buccal samples were collected and DNA was isolated using standard protocols. SNPs in the 3′ and 5′ UTR regions were analyzed by polymerase chain reaction based techniques followed by subsequent electrophoresis analysis. The gene–behavior association analysis suggests that oxytocin receptor gene polymorphisms have an impact in both breeds on (i) proximity seeking towards an unfamiliar person, as well as their owner, and on (ii) how friendly dogs behave towards strangers, although the mediating molecular regulatory mechanisms are yet unknown. Based on these results, we conclude that similarly to humans, the social behavior of dogs towards humans is influenced by the oxytocin system