The question of the reasons for the extreme variation in morbidity among the gene carriers of acute porphyria and the great diversity of the precipitating factors are approached by the aid of a model of interacting genomic circuits. It is based on the current paradigm of the acute porphyric attack as a result of a toxic proximal overload of the enzyme-
deficient heme-biosynthetic patway. Porphyrogenic influx of precursors is seen as a consequence of uncontrolled induction of its gate-keeping enzyme, ubiquitous 5-aminolevulinate synthase (ALAS1), due to attenuated post-translational control of the enzyme combined with activated gene transcription. Focus is directed on the genomic
control of the master-regulator of ALAS1-transcription, the nuclear receptor pair constitutively active receptor (CAR) and pregnane xenobiotic receptor (PXR). On activation by their ligands, i.e. lipophilic drugs, solvents, alcohols, hormonal steroids and biocides, these DNA-binding proteins transform xenobiotic or steroid stimuli to coordinated
activations of gene transcription-programs for ALAS1 and apo-cytochromes P450 (apo-CYPs), thus effecting the formation of xenobiotic-metabolizing cytochrome P450 enzymes. The potency of the CAR/PXR-transduction axis is enhanced by co-activators generated in
at least four other genomic circuits, each triggered by different external and internal stimuli clinically experienced to be porphyroge
nic, and each controlled by co-activating and co-repressing modulators. The expressions of the genes for CAR and PXR are thus augmented by binding glucocorticoid receptor (GR) activated by a steroid hormone, e.g, cortisol generated in fasting, infection or different forms of stress. The promotor regions of ALAS1 and apoCYPs contain binding sites for at least three co-activating transcription factors enhancing CAR/PXR transduction: i.e. the ligand-independent growth hormone (GH)-pulse controlled hepatocyte nuclear factor 4 (HNF4), the insulin-responsive forkhead box class O-(FOXO) protein pathway activated in stress and infection, and the proliferator-activated receptor gamma co-activator 1 al
pha (PGC-1alpha) circuit responding to glucagon liberated in fasting. Many interactions and cross-talk take place within the tangle of genomic circuits that control ALAS1-transcription, which may explain the extreme inter- and intra-individual variability in morbidity in acute porphyria. Reasons for gender-differences are found in sex-dependent control of HPA- and GH-activity as well as in direct, or GR-mediated effects on CAR/PCR activation. Constitutional differences in individual porphyric morbidity may be discussed along lines of mutations or duplications of genes for co-activating or co-repressing nuclear proteins active at different levels within the circuits.
The paper discusses the history of the relation between feminist scholarship and cultural anthropology as two ways of thinking about culture and social relationships. It focuses in particular on the feminist critique of the anthropological theory and ethnographic research. In points out the different epistemological and political standpoints of feminism and anthropology as the sources of the tensioned relationship between these two traditions of thinking about culture.
„Mecenáš věnoval jmění pražské ZOO,“ proletěla před dvěma lety jako blesk tiskem zpráva o daru v hodnotě více než 50 milionů od Stanislava Rákose, kterého znali hlavne chovatelé exotických ptáků doma i v zahraničí. Byl totiž nejen chovatelem a činovníkem chovatelského klubu, ale také vynikajícím organizátorem výstav a mezinárodních setkání. Právě on stál např. u zrodu tradice vyhlášené výstavy exotů v Botanické zahradě PřF UK Na Slupi. Některá média připodobnila dárce třeba k zakladateli „Nadace Bohuslava Jana Horáčka Českému ráji“ (viz např. AB 1/2006), nikde však nepadla ani zmínka, že Stanislav Rákos pracoval dlouhá leta v Akademii věd. To mi prozradil ředitel Ústavu teoretické a aplikované mechaniky AV ČR prof. Miloš Drdácký, s nímž jsme také navštívili mecenášovu životní souputnici paní Ludmilu Rákosovou. and Marina Hužvárová.
In the course of cytogenetic studies on Alegoria castelnaui Fleutiaux & Sallé 1889 (Coleoptera: Tenebrionidae: Tenebrioninae: Ulomini) from Guadeloupe, a number of adult specimens were dissected. A larva was found in the abdomens of almost all of the females. The karyotype, 20,XX / 20,Xyp, and the presence of heterochromatin at multiple chromosomal locations, of the larvae and adults were similar, which excludes parasitism and indicates viviparous reproduction. The adverse habitat of the adults, i.e., putrid and fermenting pseudo-stems of banana trees rather than geo-climatic conditions, may explain the occurrence of viviparity in this species. This is the first example of (ovo-)viviparity in the Ulomini tribe and among New World Tenebrionidae. A. castelnaui is regularly collected on banana trees infested with the weevil Cosmopolites sordidus Germar, 1824, a major pest of banana trees around the word. The coexistence of these two species on banana trees may be coincidental but another Ulomini species, Eutochia pulla Erichson 1843, is described as an egg predator of C. sordidus in Africa and therefore, A. castelnaui could also be a predator of this pest.