Digitális bevándorlók és bennszülöttek – a digitális tudásmegosztás és interaktivitás lehetőségei

A kortárs szociológiában parázs vita zajlik a jelenlegi társadalmak jellegéről, s ezen belül is a technológiák, az információ, a kommunikáció és kooperáció szerepéről (Machlup, 1962; Drucker, 1969; Bell, 1976). Gyakran elhangzik, hogy az információs társadalom beköszönte már a küszöbön áll, habár a szakértők között nincs konszenzus a tekintetben, hogy valójában mi nevezhető és mi nem információs társadalomnak. Abban viszont egyetértenek, hogy a 1970-es években olyan jelentős átalakulás kezdődött, amely alapvetően módosította a társadalmak működési módját. Az információ hatalommá vált és önálló értéket kapott, az „érvényes tudás” elavulási ideje felgyorsult, és álladó követelménnyé vált az élethosszig tartó tanulás. Az emberiség közös tudása, a kultúra, a tudomány fejlődése várhatóan robbanásszerű változásokat idéz majd elő

Waterpipe. The rethinking of an ethnical practice’s meaning in city

The paper attempts to examine the multicultural society of Budapest in the context of the Oriental tradition brought by the Arab, Turkish and Persian immigrants. The author presents the smoking of waterpipe as an object of a transfer from immigrants custom into general fashion. According to the author, by using sheesha the transmitters make effort to create familiarity and feeling like at home. Nevertheless, this practice dislodged from the original context (or users) and became a fashionable mean to create or to support social circles. This is a good example of general question of a process by which ethnic traditions and customs become parts of life in multicultural environment of big cities nowadays

The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of Membrane Transport

O-linked N-acetylglucosamine (O-GlcNAc) is a posttranslational modification that is increasingly recognized as a signal transduction mechanism. Unlike other glycans, O-GlcNAc is a highly dynamic and reversible process that involves the addition and removal of a single N-acetylglucosamine molecule to Ser/Thr residues of proteins. UDP-GlcNAc—the direct substrate for O-GlcNAc modification—is controlled by the rate of cellular metabolism, and thus O-GlcNAc is dependent on substrate availability. Serving as a feedback mechanism, O-GlcNAc influences the regulation of insulin signaling and glucose transport. Besides nutrient sensing, O-GlcNAc was also implicated in the regulation of various physiological and pathophysiological processes. Due to improvements of mass spectrometry techniques, more than one thousand proteins were detected to carry the O-GlcNAc moiety; many of them are known to participate in the regulation of metabolites, ions, or protein transport across biological membranes. Recent studies also indicated that O-GlcNAc is involved in stress adaptation; overwhelming evidences suggest that O-GlcNAc levels increase upon stress. O-GlcNAc elevation is generally considered to be beneficial during stress, although the exact nature of its protective effect is not understood. In this review, we summarize the current data regarding the oxidative stress-related changes of O-GlcNAc levels and discuss the implications related to membrane trafficking

CAR modified T cells resist TGF-b mediated repression through engineered IL-7 triggered IL-2 signaling

Adoptive cell therapy with chimeric antigen receptor (CAR) redirected T cells induces spectacular regressions of leukemia and lymphoma, but failed so far in the treatment of solid cancer. One of the causes is the repression of T cell activity, especially T cell proliferation through TGF-b present in the tumor microenvironment. Here we show that T cells with a second generation CAR containing a CD28 signaling domain can overcome the suppression in T cell proliferation, in contrast to T cells with a 4-1BB-containing CAR. The resistance to TGF-b activity depends on the secretion of IL-2, which is induced via CD28-mediated activation of the kinase Lck. Deletion in the LCK binding motif of the CD28 domain of the CAR (CD28DLCK-z) was able to abrogate CAR-induced IL-2 secretion and the resistance of T cell proliferation in the presence of TGF-b. However, IL-2 secreted from activated CAR T cells also sustains suppressive Treg cells at the tumor site, thus impairing the anti-tumor response. To generate enhanced CAR T cells we sought to replace CD28-mediated IL-2 secretion by an alternative cytokine, which mediates an IL-2-like signal in trans for providing TGF-b resistance. In this context, expression of IL-7 in CD28DLCK-z CAR T cells mediated TGF-b resistance equivalent to IL-2. Since the IL-7 receptor is downregulated after T cell activation we further modified CD28DLCK-z CAR T cells with a hybrid cytokine receptor, which provides IL-2R b-chain signaling upon binding of co-expressed transgenic IL-7. The strategy minimizes the detrimental effects of secreted IL-2 and at the same time improves the CAR T cell activity against TGF-b+ tumors in vivo. Our data provide proof that editing the CD28 signaling capacities and establishing a CAR induced autocrine loop by synthetic biology can make CAR T cells more potent in the hostile environment of solid tumors

Az átmenetifémionok peptidekkel alkotott komplexei. A fémion-fehérje kölcsönhatás modellezése. = Transition metal complexes of peptides. Models of the metal ion protein interactions.

1. Multihisztidin peptidek réz(II)- és cink(II)komplexei: A hisztidin nitrogén donoratomok a peptidek elsődleges fémkötőhelyei. Ezek koordinációjával makrokelátok képződhetnek, amelyek stabilitása a hisztidinek számától és távolságától függ. A karboxilcsoportok jelenléte a cink(II)komplexek stabilitását növeli. A réz(II)ionok az amidcsoport deprotonálódását is indukálhatják, ami többmagvú komplexek képződéséhez vezet. A megkötött rézionok száma megegyezik a hisztidinek számával. 2. A prion protein peptid fragmenseinek fémkomplexei: Az oktarepeaten kívüli hisztidinek is stabilis rézkötőhelyek. A HuPrP(84-114) fragmensre kapott eredmények szerint a kötési helyek stabilitási sora: His111 > His96 >> His85. Egyéb átmenetifémek komplexeit is tanulmányoztuk, amelyek stabilitási sora a következő: Pd(II) > Cu(II) > Ni(II) > Zn(II) > Cd(II) ~ Co(II) > Mn(II). 3. Az amyloid-? peptid réz(II)komplexei: Az A?(1-16) peptidnek kiugróan nagy rézionaffinitása van. A terminális aminocsoport az elsődleges fémkötőhely, amit a hisztidinek koordinációja követ. Egy A?(1-16) molekula 4 réziont képes megkötni. Az egy- két- és három-magvú komplexeknek koordinációs izomerjei lehetnek, de a terminális aminocsoport és a szomszédos amidnitrogének koordinációja preferált. | 1. Copper(II) and zinc(II) complexes of multihistidine peptides: Histidyl residues are the primary metal binding sites resulting in the formation of macrochelates. The stabilities of macrochelates are influenced by the number and location of histidyl residues. The stability of zinc(II) complexes is enhanced by the presence of carboxylate functions. Formation of polynuclear complexes has also been detected and their nuclearities correspond to the number of histidyl sites. 2. Metal binding affinity of prion peptide fragments: Histidyl residues outside the octarerepat domain are effective copper binding sites. The results obtained for the copper(II) complexes of HuPrP(84-114) revealed the following stability order: His111 > His96 >> His85. Complex formation with several other transition elements has also been studied and their stability order: Pd(II) > Cu(II) > Ni(II) > Zn(II) > Cd(II) ~ Co(II) > Mn(II). 3. Copper(II) complexes of amyloid-? peptide fragments: A?(1-16) has an outstanding affinity towards the complexation with copper. The terminal amino group is the primary metal binding site, followed by the coordination of histidyl residues. One molecule of A?(1-16) can bind as much as four copper(II) ions. Various coordination isomers of the mono-, di- and tri-nuclear complexes can exist with a preference for the coordination via the terminal amino and subsequent amide groups