Enantioselective Synthesis of 8-Hydroxyquinoline Derivative, Q134 as a Hypoxic Adaptation Inducing Agent

Hypoxia is a common feature of neurodegenerative diseases, including Alzheimer’s disease that may be responsible for disease pathogenesis and progression. Therefore, the hypoxia-inducible factor (HIF)1 system, responsible for hypoxic adaptation, is a potential therapeutic target to combat these diseases by activators of cytoprotective protein induction. We have selected a candidate molecule from our cytoprotective hydroxyquinoline library and developed a novel enantioselective synthesis for the production of its enantiomers. The use of quinidine or quinine as a catalyst enabled the preparation of enantiomer-pure products. We have utilized in vitro assays to evaluate cytoprotective activity, a fluorescence-activated cell sorting (FACS) based assay measuring mitochondrial membrane potential changes, and gene and protein expression analysis. Our data showed that the enantiomers of Q134 showed potent and similar activity in all tested assays. We have concluded that the enantiomers exert their cytoprotective activity via the HIF1 system through HIF1A protein stabilization

The Sovietisation of Hungarian Geography, 1945–1960. Mitteilungen der Österreichischen Geographischen Gesellschaft|Mitteilungen der Österreichischen Geographischen Gesellschaft - Band 154 154|

Following Hungary’s serious losses of territory after World War I, geography becameregarded as a major tool for the scientific substantiation of claims to territorialrevision by the political elite. The discipline’s position was strengthened, and the vastmajority of geographers supported the political goals of the regime. After 1945, however,Hungary became a part of the Soviet occupation zone. After the violent establishmentof the Communist system, geography was found guilty of having served the interwarpolitical regime. The old ‘reactionary’ and ‘bourgeois’ geography was demolished anda new, Marxist-Leninist geography on Soviet principles was established. The latter wasbased on the concept of economic determinism: ‘physical’ and ‘economic’ geographywere strongly distinguished. Geography became a part of national economic planning.State research institutes and those of the Academy of Sciences, and the CentralPlanning Office became the most important ‘centres of calculation’ where Soviet-type‘big science’ was established. Several ‘old’ geographers were pensioned off or exiledfrom academia; others were driven to the periphery or forced to compromise withthe system. In the meanwhile, all important positions were given to politically loyal‘newcomers’. The international orientation of Hungarian geography changed as well:former German and French influence was followed by a stable orientation towards‘friendly’ Socialist countries, especially towards the USSR

Knowledge and Power in Sovietized Hungarian Geography

The history and geography of science offer ample evidence of how those in power try to control knowledge and education, how certain regimes tried to manipulate scientific disciplines to benefit their own interests, how some disciplines adapted to radical changes in political systems and adjusted their theoretical concepts to new ideologies, and what efforts these disciplines made to appear “useful” to those in power. This article examines the means used by the Communist regime in Hungary after World War II to “conquer” science and colonize geography. Researchers have richly documented how Central and Eastern Europe became objects of “Soviet colonialism”; how these countries were turned into economic fiefdoms of the Soviet empire, with economic production undertaken on a command basis and trade permissible only through the Communist alliance; and what consequences this development had on various fields. But scholars working in the history and geography of science still pay little attention to the intellectual transformation that took place in the discipline of geography in these countries as of the late 1940s. For this reason, we aim in this essay to contribute to a better understanding of these issues by revealing how Hungarian geography was colonized during the 1950s. We show how the Communist system crushed “the old geography” in order to establish Hungarian Marxist-Leninist geography. We reveal how geographic knowledge, like knowledge in general, became “a form of power, and by implication violence”. We describe different epistemological cultures that infl uenced and determined the approaches, methods, social tasks, and educational role of Hungarian geography between the world wars and after World War II. We analyze the effect that Marxist-Leninist ideology had on Soviet geography in this period. Furthermore, we investigate how a colonizing ideology dominated Hungarian geography, how the institutional structure of geography was transformed, and how the career paths of the “old” geographers continued. We also outline who became the “new” geographers and how, and describe the new tasks set for MarxistLeninist geography in Hungary

Személyiségvonások a párválasztásban: homogámia és/vagy szexuális imprinting = Personality traits in the mate choice: homogamy and/or sexual imprinting

Korábbi, az arc elemzésén alapuló vizsgálataink azzal a következtetéssel zárultak, hogy a fenotípusos illesztés modellje mellett bizonyos szexuális imprinting jellegű mechanizmusok is részt vesznek a párválasztásban. Jelenlegi kutatásunkban arra vagyunk kíváncsiak, hogy a személyiségvonások esetében is kimutatható-e a szexuális imprinting hatása. Vizsgálatunkban 49 házaspár és azok szülei vettek részt, összesen 294 személy. Mindegyikükkel felvettük a Caprara-féle BIG FIVE kérdőívet, és a házaspárokat a s-EMBU retrospektív attachement teszt kitöltésére is megkértük. Hasonlóságot találtunk a férfiak felesége és anyjuk között a BFQ Szociális Kívánatosság és a Lelkiismeretesség faktorában, valamint kimutattuk, hogy az anyai nevelési stílus befolyásolja a férfiak párválasztását. A s-EMBU anyai Elutasítás faktora az Érzelmi stabilitás, az Érzelmi melegség faktor pedig a Barátságosság vonásban fejti ki hatását. Az anyai nevelési stílus pontosabb elemzésekor azt a meglepő eredményt kaptuk, hogy az anyjukkal „rosszabb” kapcsolatban lévő férfiak azok, akik igyekeznek anyjukhoz hasonló feleséget választani az Érzelmi stabilitás és a Szociális Kívánatosság személyiségvonásban. A női párválasztásban csupán egy tendencia jelzi a szexuális imprinting működését: az apjuktól magas Szeretetet tapasztaló nők férje és apjuk a Lelkiismeretesség faktorban hasonlítanak egymáshoz. | We have made an attempt at demonstrating the effect of sexual imprinting mechanism on human mate choice. In our former studies, we had focused on facial similarities between couples, now we wondered if homogamy is represented in personality characters, as well. Two hundred ninety six participants (49 couples and their parents) filled in the Caprara’s BIG FIVE Questionnaire. The couples were also asked to complete the s-EMBU retrospective attachment test (including Emotional warmth, Rejection, Overprotection scales). Significant resemblances were found between the males’ wife and mother in Social Desirability and Conscientiousness traits of the BFQ. Our results on the effects of maternal rearing behavior style on their son’s mating revealed controversial patterns. Scores on Rejection scale of s-EMBU were associated with Emotional Lability, and Emotional Warmth with Agreeableness trait, which supports our expectation. However, another analysis of maternal rearing has shown that those men who developed an unfavorable attachment with their mother during childhood would be attracted to women who are similar to her in Emotional Lability and Social Desirability traits, which seems to contradict our hypothesis. As for women’s mate choice, only one tendency has been revealed for supporting the sexual imprinting hypothesis: those women who had experienced high Emotional Warmth from their father during childhood chose men who resembled their father in Conscientiousness factor of the BFQ

Thermal Manipulation of Human Bone Collagen Membrane (SoftBone) and Platelet-Rich Fibrin (PRF) Membranes

Resorbable barrier membranes, including platelet-rich fibrin (PRF) and collagen membranes, can play a key role in guided bone regeneration surgeries (GBR) in dentistry. A new collagen membrane made of partially decalcified allogeneic cortical bone, termed SoftBone membrane (SB), was produced by West Hungarian Regional Tissue Bank. It can be easily adapted to diverse surfaces. Fresh and freeze-dried folded-PRF membranes were compared with freeze-dried SB. Important properties of membranes were reported (moisture content, rehydration capacity, and resistance against proteolytic enzyme). The SB exhibited the best resistance against enzymatic digestion on day 21, its weight was 34% of the original. Fresh F-PRF (folded PRF) disintegrated on the 11th day, while the freeze-dried F-PRF membrane dissolved completely on day 8. The thermal manipulation of the F-PRF membrane using freeze-drying has advantages and also disadvantages in comparison to the fresh one

Mannich Curcuminoids as Potent Anticancer Agents

A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen–Schmidt condensation sequence. Structure–activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model. The novel spectrum of activity of these Mannich curcuminoids warrants further preclinical investigations

Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides

The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7- carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM)

Mannich Curcuminoids as Potent Anticancer Agents

A series of novel curcuminoids were synthesised for the first time via a Mannich-3CR/organocatalysed Claisen–Schmidt condensation sequence. Structure–activity relationship (SAR) studies were performed by applying viability assays and holographic microscopic imaging to these curcumin analogues for anti-proliferative activity against A549 and H1975 lung adenocarcinoma cells. The TNFα-induced NF-κB inhibition and autophagy induction effects correlated strongly with the cytotoxic potential of the analogues. Significant inhibition of tumour growth was observed when the most potent analogue 44 was added in liposomes at one-sixth of the maximally tolerated dose in the A549 xenograft model. The novel spectrum of activity of these Mannich curcuminoids warrants further preclinical investigations