Dynamic expression of homeostatic ion channels in differentiated cortical astrocytes in vitro

The capacity of astrocytes to adapt their biochemical and functional features upon physiological and pathological stimuli is a fundamental property at the basis of their ability to regulate the homeostasis of the central nervous system (CNS). It is well known that in primary cultured astrocytes, the expression of plasma membrane ion channels and transporters involved in homeostatic tasks does not closely reflect the pattern observed in vivo. The individuation of culture conditions that promote the expression of the ion channel array found in vivo is crucial when aiming at investigating the mechanisms underlying their dynamics upon various physiological and pathological stimuli. A chemically defined medium containing growth factors and hormones (G5) was previously shown to induce the growth, differentiation, and maturation of primary cultured astrocytes. Here we report that under these culture conditions, rat cortical astrocytes undergo robust morphological changes acquir- ing a multi-branched phenotype, which develops gradually during the 2-week period of culturing. The shape changes were paralleled by variations in passive membrane properties and background conductance owing to the differential temporal development of inwardly rectifying chloride (Cl−) and potassium (K+) currents. Confocal and immunoblot analyses showed that morphologically differentiated astrocytes displayed a large increase in the expression of the inward rectifier Cl− and K+ channels ClC-2 and Kir4.1, respectively, which are relevant ion channels in vivo. Finally, they exhibited a large diminution of the intermediate filaments glial fibrillary acidic protein (GFAP) and vimentin which are upregulated in reactive astrocytes in vivo. Taken together the data indicate that long-term culturing of cortical astrocytes in this chemical-defined medium promotes a quiescent functional phenotype. This culture model could aid to address the regulation of ion channel expression involved in CNS homeostasis in response to physiological and pathological challenge

IMPACT OF DIFFERENT DOSING STRATEGIES OF NIVOLUMAB IN PATIENTS WITH SOLID TUMORS: ITALIAN SINGLE CENTER ANALYSIS

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Tracking Future Graphics Education through Virtual Dystopian Spaces

This paper aims at envisioning prospective fragments of future scenarios in the field of graphics education in architecture. The inspiration comes from the recent rapid evolution affecting the approach to digital representation in the Schools of Architecture. After a long «dormant» phase, the digital and the internet have shown a tremendous rise, not only on the academic channels but also in our everyday life. In addition, the appearance of Covid-19 worldwide has made them necessary supports for and virtual surrogates of plenty of actions traditionally happening face to face. Consequently, for about a year now, technology has been at the core of the massive communication strategies activated to mitigate the effects of social distancing. Showing in addition an interesting contrast: while on the one hand the real world seems to have been widely flanked by, or, sublimated into dystopic «virtual bubbles», on the other hand, just that virtual bubbles seem to tend to acquire a status of «real places» in a large part of our lives. Which in our opinion deserves our disciplinary attention, since that new pretentious real places are made of the same matter of representations in fact. Here languages become relevant. Then our research question is: may the mentioned dystopian visionary worlds generated by the digital be also of help, apart from their instant fascination, in envisioning fragments of the future operational scenarios waiting for us in architectural graphics education

Searching for Human Variables in the Discussion about the Development of Virtually Enhanced Spaces

When trying to observe the possible future developments of different forms of communication and socialization, today traditionally linked to physical environments, it often seems inevitable that one day they may change through the increasing integration of technological solutions capable of superimposing alternative virtual universes to our physical world. Virtual spaces, once generated through rigid rules and representations derived from drastic geometric reductions of reality, are becoming more and more advanced, obeying increasingly more dynamic systems, and sometimes giving the appearance of being able to imitate life itself. Can this guess match the reality? In one of our studies in progress, we talked about how technology is encroaching on «dystopian» aspects and that, in a more or less evident way, this happens in many aspects of reality including that of the generation of geometric shapes. In particular, the latest trends on which the modelling principles develop towards a procedural logic that has its core purpose in solving functional problems, first of all, and also in reaching out to the market logic, developing styles suitable to attracts attention from specific target audiences. The current discussion wants to bring the topic back to the human being and to nature seen as: «Man is the measure of all things» phrase expressed by Protagora, generally interpreted as the non-existence of an objective truth, that is, the existence of a truth not the same for everyone. The ease of translating into algorithms of the generative processes of geometric shapes often leads to the creation of results detached from this kind of logics and which in the past, since the Renaissance age, are based on modulus and on the proportional relationships among the parts and of each part with the whole, moving from «measurability» to «commensurability». The aim is to use in a modern language the same codes and principles on which nature is based and communicates, starting for example from the growth laws of living organisms (Fibonacci series, golden section, etc.), from the principle of similitude and from the law of least effort

Architectural Geometry and Graphics Education some Retrospective Reflections from Italy Across Three Generations

This work would focus on the changes in geometry and graphics education for architects occurred in the Italian university in the last two decades, mainly involving three generations of academics, researchers, young prospective scholars, in the occasion represented by the same authors listed within the work title

Architectural Geometry and Graphics Education Some Retrospective Reflections from Italy Across Three Generations

This work aims to focus on the changes in Geometry & Graphics education addressed to the architects occurred in the Italian university in the last two decades, mainly involving three generations of academics, researchers, young prospective scholars, in this occasion represented by the authors listed within the work title. Reason for the choice is to stimulate a discussion among these generations, especially in the desirable light of the opportunity – despite the Covid-19 restrictions – to share issues with educators operating in other universities worldwide during the conference days, looking for ideas and hypotheses for updating our academic curricula and researches. In this story, it is to be mentioned the relevant role played in our country by the Unione Italiana Disegno (UID), founded in 1980, and since 2014 an institutional member of the International Society for Geometry and Graphics (ISGG), also thanks to the convinced determination of its former president, professor Vito Cardone, unforgotten member and leader of our Italian academic community. Several loved colleagues and friends are no longer with us today, without whose passion, teachings and wisdom we could not have been here to tell this story, as well as, maybe, we would not have had the lucky chance to spend our academic life enjoying Geometry and Graphics. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG

DOWN- REGULATION OF MLL-AF9,MLL,HOXA9,HOXA10, AND MEIS1 EXPRESSION IS NOT OBLIGATORY FOR MONOCYTE- MACROPHAGE MATURATION IN AML -M5 CELL LINES CARRYNG t(9;11)(p22;q23)

The MLL-AF9 oncogene originates from the translocation t(9;11)(p22;q23), which is mainly associated with monocytic acute myeloid leukaemia (AML-M5; FAB-classification). In AML-M5 THP-1 cells carrying t(9;11) (p22;q23) and expressing MLL-AF9, we previously showed that MLL-AF9 expression is down-regulated during monocyte-macrophage maturation. We have subsequently observed that in a 'rapid-growing' variant of the THP-1 cell line (THP-1-R) MLL-AF9 down-regulation does not occur. MLL fusion proteins (including MLL-AF9) deregulate MYC transactivation activity, and both presence and absence of MYC down-regulation have been reported during monocyte-macrophage maturation in THP-1 cells. In the present study, we analyze the expression patterns of MLL-AF9, MLL wild-type and MYC after induction of monocyte-macrophage terminal differentiation in the AML-M5 cell lines, THP-1, THP-1-R, Mono-Mac-6 (MM6) and MOLM-13, all of which carry t(9;11)(p22;q23) and express MLL-AF9. RT-PCR analysis indicated that down-regulation of MLL-AF9, MLL or MYC is not necessary to abolish malignant phenotypes by induction of terminal monocyte-macrophage differentiation in leukaemic cells carrying t(9;11)(p22;q23)