Phylogenetic screening of the human genome: identification of differentially hybridizing repetitive sequence families

The phi-screen, a method of phylogenetic screening, can be employed to detect repetitive sequence families that differentially hybridize between closely related species. Such differences may involve sequence divergence or variations in copy number, including total presence versus absence of a family of repeated DNA. We present the results of a phi-screen comparing the human genome to that of the prosimian, Galago crassicaudatus. Three human repetitive families that are divergent or not present in galago have been detected. One of these families is described in detail; it is similar among the anthropoids but is present in a lower copy number and/or divergent form in prosimians. The family is clearly related to the transposon-like human element (THE) described by Paulson et al. (1985). THEs have long terminal repeats reminiscent of retroviruses but are unique in that they have no sequence similarity to known mammalian retroviruses. The sequence of a solo long terminal repeat, found unassociated with THE internal sequence, is presented. This family member, THE p2, is bordered by a 5-bp target-site repeat and is interrupted by the insertion of an Alu element. A solo THE element sequenced by Wiginton et al. (1986) contains an insertion of Alu at precisely the same position as does THE p2.      

Axospinal synapses in the forebrain cortex of aquatic and terrestrial turtles

An electron microscopical investigation of synaptic organization of the superficial plexiform layer of three forebrain cortical zones (hippocampal, dorsal and piriform) in two aquatic and two land Chelonia species has been performed. As demonstrate the data obtained and those from the literature, the main elements of the axo-spinal complexes (spines--synapses--neural terminals) possess both stability properties, contributing to structural firmness of the contacts and their reliability during activities, and plastisity ensuring the maintenance of dynamic equilibrium and a possibility for adequate rearrangements. Under normal conditions, the functional shifts in ultrastructure of the synaptic apparatuses are, possibly, so negligible that they cannot mask certain specific fractures of the synaptic organization of the neural centers. When comparing structures of the axo-spinal complexes in functionally dissimilar cortical zones, more constant, common for all species of Chelonia studied signs are definitely revealed. They characterize a certain level of the neural processes integration. There are signs more variable, evidently, ensuring adaptive rearrangements within limits of the given level of the interneuronal connections organization which can be considered as ecological and species-specific peculiarities.     

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study

Background  

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India     

Periplasmic superoxide dismutase from Desulfovibrio desulfuricans 1388 is an iron protein

It is shown that the genome of the sulfate-reducing bacterium Desulfovibrio desulfuricans 1388 contains a superoxide dismutase (SOD) gene (sod). The gene encodes an export signal peptide characteristic for periplasmic redox proteins. The amino acid sequence showed high homology with iron-containing SODs from other bacteria. Electrophoretically pure SOD was isolated from the periplasmic fraction of bacterial cells by FPLC chromatography. Like other Fe-SODs, D. desulfuricans 1388 superoxide dismutase is inhibited by H2O2 and azide, but not by cyanide.     

Electron transfer in the complex of membrane-bound human cytochrome P450 3A4 with the flavin domain of P450BM-3: The effect of oligomerization of the heme protein and intermittent modulation of the spin equilibrium

We studied the kinetics of NADPH-dependent reduction of human CYP3A4 incorporated into Nanodiscs (CYP3A4-ND) and proteoliposomes in order to probe the effect of P450 oligomerization on its reduction. The flavin domain of cytochrome P450-BM3 (BMR) was used as a model electron donor partner. Unlike CYP3A4 oligomers, where only 50% of the enzyme was shown to be reducible by BMR, CYP3A4-ND could be reduced almost completely. High reducibility was also observed in proteoliposomes with a high lipid-to-protein ratio (L/P = 910), where the oligomerization equilibrium is displaced towards monomers. In contrast, the reducibililty in proteoliposomes with L/P = 76 did not exceed 55 ± 6%. The effect of the surface density of CYP3A4 in proteoliposomes on the oligomerization equilibrium was confirmed with a FRET-based assay employing a cysteine-depleted mutant labeled on Cys-468 with BODIPY iodoacetamide. These results confirm a pivotal role of CYP3A4 oligomerization in its functional heterogeneity. Furthermore, the investigation of the initial phase of the kinetics of CYP3A4 reduction showed that the addition of NADPH causes a rapid low-to-high-spin transition in the CYP3A4-BMR complex, which is followed by a partial slower reversal. This observation reveals a mechanism whereby the CYP3A4 spin equilibrium is modulated by the redox state of the bound flavoprotein.