LIME: A New Membrane Raft-associated Adaptor Protein Involved in CD4 and CD8 Coreceptor Signaling

Lymphocyte membrane rafts contain molecules critical for immunoreceptor signaling. Here, we report identification of a new raft-associated adaptor protein LIME (Lck-interacting molecule) expressed predominantly in T lymphocytes. LIME becomes tyrosine phosphorylated after cross-linking of the CD4 or CD8 coreceptors. Phospho-LIME associates with the Src family kinase Lck and its negative regulator, Csk. Ectopic expression of LIME in Jurkat T cells results in an increase of Csk in lipid rafts, increased phosphorylation of Lck and higher Ca2+ response to CD3 stimulation. Thus, LIME appears to be involved in regulation of T cell activation by coreceptors

Negative Regulation of Mast Cell Signaling and Function by the Adaptor LAB/NTAL

Engagement of the Fcɛ receptor I (FcɛRI) on mast cells and basophils initiates signaling pathways leading to degranulation. Early activation events include tyrosine phosphorylation of two transmembrane adaptor proteins, linker for activation of T cells (LAT) and non–T cell activation linker (NTAL; also called LAB; a product of Wbscr5 gene). Previous studies showed that the secretory response was partially inhibited in bone marrow–derived mast cells (BMMCs) from LAT-deficient mice. To clarify the role of NTAL in mast cell degranulation, we compared FcɛRI-mediated signaling events in BMMCs from NTAL-deficient and wild-type mice. Although NTAL is structurally similar to LAT, antigen-mediated degranulation responses were unexpectedly increased in NTAL-deficient mast cells. The earliest event affected was enhanced tyrosine phosphorylation of LAT in antigen-activated cells. This was accompanied by enhanced tyrosine phosphorylation and enzymatic activity of phospholipase C γ1 and phospholipase C γ2, resulting in elevated levels of inositol 1,4,5-trisphosphate and free intracellular Ca2+. NTAL-deficient BMMCs also exhibited an enhanced activity of phosphatidylinositol 3-OH kinase and Src homology 2 domain–containing protein tyrosine phosphatase-2. Although both LAT and NTAL are considered to be localized in membrane rafts, immunogold electron microscopy on isolated membrane sheets demonstrated their independent clustering. The combined data show that NTAL is functionally and topographically different from LAT

Non–T Cell Activation Linker (NTAL): A Transmembrane Adaptor Protein Involved in Immunoreceptor Signaling

A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non–T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcγ- and Fcɛ-receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non–T cells

Rozhovor Britských listů 366. Chtějí v ČR skutečně vyvraždit všechny starší lidi? [Britské listy Interview 366. Are the authorities in the Czech Republic really intending to kill off all the older citizens?]

Jan Čulík discusses the incredibly catastrophic pandemic situation and the incompetence and inactivity of the Czech authorities with the leading Czech immunologist Professor Václav Hořejší. The interview was broadcast by the Czech cable TV station Regionalnitelevize.cz from Wednesday 24th February 2021

Rozhovor Britských listů 378. Koronavirus: ČR je na dobré cestě [Britské listy Interview 378. Coronavirus: The Czech Republic is beginning to cope]

The Czech Republic still has a relatively high level of infection, although it is now decreasing. What does immunologist Professor Václav Hořejší think? He talks to Jan Čulík about the current pandemic situation. The interview was broadcast by the Czech cable TV station Regionalnitelevize.cz from 7th April 2021

Rozhovor Britských listů 421. Měla by se v ČR zrušit všechna protikoronavirová opatření? [Britské listy Interview 421. Should all anti-coronavirus measures be abolished in the Czech Republic?]

Jan Čulík talks to immunologist Professor Václav Hořejší about the current coronavirus situation in the Czech Republic and about what might happen with the pandemic in future. This interview was broadcast on the Czech cable TV station Regionalnitelevize.cz from 3rd September 2021

Rozhovor Britských listů 352. Koronavirus: Situace v ČR je opravdu hrozná. Co s tím? [Britské listy Interview 352. Coronavirus: the situation in the Czech Republic is really alarming. What to do next?]

In connection with the drastically deteriorating pandemic situation in the Czech Republic, Jan Čulík talks again to Professor Václav Hořejší, a leading Czech immunologist, about what to do next. The interview was broadcast by the Czech cable TV station Regionalnitelevize.cz from Friday 8th January 2021

Using virtual reality in geography teachers’ training

Virtuální realita se dnes stává běžnou součástí našich životů a její využití je značně široké. Užitek najde i ve vzdělávání, například využívání aplikace Google Expeditions na základních školách. tento článek pojednává o aplikaci virtuální reality v univerzitním prostředí, konkrétně při přípravě budoucích učitelů. ti v prostředí virtuální reality mohou zdokonalovat své dovednosti v tzv. virtuální třídě, která se dle dosavadních výsledků jeví jako vhodný doplněk praxí ve školách, jejich reflexí a výuky oborových didaktik.Virtual reality (VR) is becoming part of everyday life and its utilization is quite wide. It can be useful also in education, e.g. see using Google Expeditions app at elementary schools. This paper deals with the use of VR at universities particularly during the teachers’ training. Future teachers may develop their teaching or speaking skills in a virtual class-room. According to the results of our pilot study, this teaching simulator can be successfully used as one of the possibilities of pedagogical training together with real life practice at school

Trénink budoucích učitelů v trenažeru Virtuální třída : pilotní studie

Virtuální učebna je aplikace založená na Unity 3D engine. Uživatel si nasadí 3D brýle a ocitne se ve virtuálním modelu třídy základní školy. V učebně je také virtuální tabule, kde může uživatel psát poznámky, stejně jako mapa s ukazovátkem. Aplikace je využívána při výuce didaktiky zeměpisu, ovšem očekává se rozšíření na další obory. V pilotní studii bylo testováno 10 studentů 1. ročníku navazujícího magisterského studia geografie, jejichž úkolem bylo představit krátké vysvětlení ve virtuální učebně, zaměřené na vybrané kritické místo kurikula zeměpisu. Před zahájením výcvikového kurzu VR studenti vyplnili dotazník se zaměřením na jejich zkušenosti se skutečnou výukou a VR. Pilotní studie byla provedena ve třech po sobě jdoucích fázích. Nejprve se studenti s virtuální učebnou seznámili (představili se a sdělili probírané geografické téma) a poskytli základní zpětnou vazbu na prostředí virtuální třídy. V další fázi představili účastníci předem připravené téma, získali zpětnou vazbu od učitelů a dalších studentů, kteří hodnotili jejich výkon, a znovu poskytli zpětnou vazbu na prostředí. V poslední fázi pilotní studie studenti znovu učili stejné téma a snažili se podat lepší výkon, reflektující komentáře z předchozí úrovně. Po dokončení procesu studenti vyplnili další dotazník, kde poskytovali anonymní komentáře k celkovému konceptu Virtuální třídy. Z výsledků pilotní studie je zřejmé, že prezentace jednotlivých studentů ve virtuální učebně je dobrým způsobem, jak otevírat oborová i didaktická témata ve výuce didaktiky. Ukázalo se, že budoucí učitelé velmi často zaměřují své učení na profesní přesnost předkládaného kurikula a méně se zabývají didaktickými aspekty učených témat - jak vysvětlit a motivovat žáky k učení atd. Schopnost vysvětlit problematické oblasti kurikula může být ve virtuální učebně systematicky rozvíjena a použitý dvoufázový přístup se jeví jako vhodný metodologický základ. Při porovnání prvního a druhého výstupu ve virtuální třídě je zřejmé, že se studenti zlepšují, takže tento simulátor pedagogické práce lze úspěšně použít jako jednu z možností pedagogického výcviku ve spojení s vlastní školní praxí. Současně jsme dospěli k závěru, že někteří studenti trpí při práci ve virtuální třídě tzv. cyber sickness a nemohou se plně soustředit. Ovšem i pro tyto studenty je trénink také prospěšný, protože se mohou zapojit do role reflexivního hodnotitele.The pilot study will be presented in a Virtual classroom environment. Virtual classroom is an application based on the Unity 3D engine. The user puts on 3D glasses, and finds himself/herself in a virtual primary, school model where several pupils can sit on the seats to interact with. There is also a virtual whiteboard in the classroom, where the user can write notes, as well as a map with a pointer. The application is used during the teaching of didactics for pre-service geography teachers, where expansion to other disciplines is expected. In the pilot study, there were 10 students of the 1st year of Geography Teaching, whose task was to present a short explanation in a virtual classroom, focused on selected critical points of the geography curriculum. Before starting the VR training coin se, the students completed a questionnaire, focusing on their experience with real teaching and VR. The pilot study was conducted in three successive stages. First, the students tried working in a virtual classroom (presented themselves and a geographic theme), provided basic feedback, and were given a virtual session at lower secondary school level. In theft next class, they presented a pre-prepared theme in a virtual classroom, received feedback from teachers and other students who evaluated theft performance according to a single evaluation form, and reflected on the work in Virtual Classroom. During the last stage of the project work, the students taught the same topic again, and tried to give a better performance, reflecting comments from the previous level. After completing the process, the students completed another questionnaire to determine their responses to the application of VR in teacher training. It is clear from the results of the pilot study that the presentation of individual students in a virtual classroom is a good way to open both subject and didactic topics in teaching didactics. It turned out that pre-service teachers very often focus their training and self-learning on the professional (disciplinary) accuracy of the presented curriculum, and are less concerned with the didactic aspects of the topics taught - how to explain and motivate pupils to learn, etc. The ability to explain the problematic areas of the curriculum can be systematically developed in a Virtual classroom, as well as the two-stage approach used, seem to be the appropriate methodological basis. When comparing the first and second performances in a virtual classroom, it is clear that students are getting better, so this pedagogical work simulator can be successfully used as one of the possibilities of pedagogical training, in conjunction with their own school practice. At the same time, we came to the conclusion that some students suffer from cyber sickness while working in a virtual classroom, and cannot fully concentrate. However, it is also beneficial for these students to be able to participate in the role of reflective evaluator and colleague for didactics lessons, using a Virtual classroom