Biomedical subjects

N Stojanovic

Publications and source records attributed to N Stojanovic.

5 recordsLinked to original sources

PubMed1994

Globin gene server: a prototype E-mail database server featuring extensive multiple alignments and data compilation for electronic genetic analysis.

The sequence of virtually the entire cluster of beta-like globin genes has been determined from several mammals, and many regulatory regions have been analyzed by mutagenesis, functional assays, and nuclear protein binding studies. This very large amount of sequence and functional data needs to be compiled in a readily accessible and usable manner to optimize data analysis, hypothesis testing, and model building. We report a Globin Gene Server that will provide this service in a constantly updated manner when fully implemented. The Server has two principal functions. The first (currently available) provides an annotated multiple alignment of the DNA sequences throughout the gene cluster from representatives of all species analyzed. The second compiles data on functional and protein binding assays throughout the gene cluster. A prototype of this compilation using the aligned 5' flanking region of beta-globin genes from five species shows examples of (1) well-conserved regions that have demonstrated functions, including cases in which the functional data are in apparent conflict, (2) proposed functional regions that are not well conserved, and (3) conserved regions with no currently assigned function. Such an electronic genetic analysis leads to many readily testable hypotheses that were not immediately apparent without the multiple alignment and compilation. The Server is accessible via E-mail on computer networks, and printed results can be obtained by request to the authors. This prototype will be a helpful guide for developing similar tools for many genomic loci.

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PubMed1993

Positive and negative regulatory elements of the rabbit embryonic epsilon-globin gene revealed by an improved multiple alignment program and functional analysis.

The epsilon-globin genes of mammals are expressed in early embryos, but are silenced during fetal and adult erythropoiesis. As a guide to defining the regulatory elements involved in this developmental switch, we have searched the sequences of epsilon-globin genes from different mammals for highly conserved segments. The search was facilitated by the development of a new program, called yama, to generate a multiple alignment of very long sequences using an improved scoring scheme. This allowed us to generate a multiple alignment of sequences from a more divergent group than previously analyzed, as demonstrated here for representatives of four mammalian orders. In parallel experiments, we constructed a series of deletion mutations in the 5' flank of the rabbit epsilon-globin gene and tested their effect on an epsilon-globin-luciferase hybrid reporter gene. These results show that 121 bp of 5' flank, containing CACC, CCAAT and ATA motifs, is sufficient for expression in erythroid K562 cells. Both positive and negative cis-acting control sequences are located between 218 and 394 bp 5' to the cap site, in a region previously proposed to be a silencer. The positive regulatory sequence contains conserved binding sites for the nuclear protein YY1 adjacent to another highly conserved sequence. The negative element contains a conserved sequence followed by a purine-rich segment. This analysis maps the upstream control sequences more precisely and points to a very complex regulatory scheme for this gene.

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PubMed1980

[Metabolism of (1-14C) cholesteryl oleate in the brain of the cat].

Following injection into the cerebral ventricles of conscious cats, cholesteryl oléate (-1-14C) was taken up, hydrolysed and included into a variety of brain lipids. The peak of uptake of cholesteryl oleate (-1-14C) into the brain tissue was obtained 4 h after its administration. The peak of hydrolysis occurred 48 h following intraventricular administration of cholesteryl oleate (-1-14C). Cholesterol esters and free fatty acids decreased, while phospholipids increased within 48 h following injection of labelled cholesteryl oleate. Small percentage of the radioactive material was found in triglycerides, monoglycerides and diglycerides. The radioactive material was found in the brain tissue surrounding the cerebral ventricles and in the cerebral cortex, but in varying amounts: the highest in the thalamus and in the caudate nucleus, while the smallest in the cerebral cortex. The labelled material in these structures increased within first 4 h after its intraventricular injection and thereafter slowly decreased, but by the end of 48 h it was still retained in appreciable amounts.

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PubMed1979

[Uptake and esterification of (4-14C) cholesterol after injection into the cerebral ventricles of conscious cats].

The brain tissue had appreciable capacity to take up and to esterify (4-14C) cholesterol from the cats cerebral ventricles. The highest values of radioactive material in the brain tissue were found 30 minutes after intraventricular injection of (4-14C) cholesterol. Thereafter, within a few hours most of the labelled cholesterol disappeared and by the end of 48 h the brain tissue retained only small amounts of it. at the same time, radioactive material was found in the peripheral venous blood, but in very small amounts. The analysis for cholesterol esters showed that about 50 % of (4-14C) cholesterol taken up by the brain tissue had undergone esterification. The rate of esterification of cholesterol within 48 h remained more or less constant, although a significant peak was noted by the end of 24 h.

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PubMed1977

[Distribution, uptake and hydrolysis of cholesterol oleate (-1-14C) in brain tissue after its injection in the cerebral ventricles of the conscious cat].

Distribution, uptake and hydrolysys of cholesteryl oleate (-1-14C) in vivo in the cat's brain were investigated. Four hours following intraventricular injection of cholesteryl oleate (-1-14C), about one third of the injected radioactivity was taken up and about 50 % of that radioactive material was hydrolysed by brain tissue. Even more, the labelled material was found in the brain tissue surrounding the cerebral ventricles as well as in the cerebral cortex, but in varying amounts: the smallest amounts were found in the cerebral cortex, while the highest were in the hypothalamus. Radioactive material was also detected in the peripheral venous blood.

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