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At least 775 records · Page 43Linked to original sources
PubMed1999

The antisense sequence of the HIV-1 TAR stem-loop structure covalently linked to the hairpin ribozyme enhances its catalytic activity against two artificial substrates.

This work is an in vitro study of the efficiency of catalytic antisense RNAs whose catalytic domain is the wild-type sequence of the hairpin ribozyme, derived from the minus strand of the tobacco ringspot virus satellite RNA. The sequence in the target RNA recognized by the antisense molecule was the stem-loop structure of the human immunodeficiency virus-1 (HIV-1) TAR region. This region was able to form a complex with its antisense RNA with a binding rate of 2 x 10(4) M(-1)s(-1). Any deletion of the antisense RNA comprising nucleotides of the stem-loop resulted in a decrease in binding rate. Sequences 3' of the stem in the sense RNA also contributed to binding. This stem-loop TAR-antisense segment, covalently linked to a hairpin ribozyme, enhanced its catalytic activity. The highest cleavage rate was obtained when the stem-loop structure was present in both ribozyme and substrate RNAs and they were complementary. Similarly, an extension at the 5'-end of the hairpin ribozyme increased the cleavage rate when its complementary sequence was present in the substrate. Inclusion of the stem-loop at the 3'-end and the extension at the 5'-end of the hairpin ribozyme abolished the positive effect of both antisense units independently. These results may help in the design of hairpin ribozymes for gene silencing.

Base Pairing↗
PubMed1998

TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer.

An oligoribonucleotide, corresponding to the Tat-interactive top half of the HIV-1 TAR RNA stem-loop, was synthesized in both the natural D- and the enantiomeric L-configurations. The affinity of Tat for the two RNAs, assessed by competition binding experiments, was found to be identical and is reduced 10-fold for both, upon replacement of the critical bulge residue U23 with cytidine. It is suggested that this interaction of the flexible Tat protein depends strongly upon the tertiary structure of a binding pocket within TAR, but not upon its handedness, and may be described by a 'hand-in-mitten' model.

Binding, Competitive↗
PubMed2000

NMR characterization of a kissing complex formed between the TAR RNA element of HIV-1 and a DNA aptamer.

This work presents the first structural analysis of an RNA-DNA complex consisting of an 18 nt RNA hairpin and a 20 nt DNA aptamer. The DNA molecule was previously selected, from a randomly synthesized library, against the transactivation response element (TAR) involved in transcriptional regulation of the HIV genome. The DNA aptamer used in the present study is an imperfect stem-loop with the sequence 5'-ACTCCCAT-3', characteristic of the selected candidates, in the apical loop. This octameric motif contains five bases complementary to the TAR loop sequence 5'-CUGGGA-3'. The use of homo- and heteronuclear NMR spectroscopy allowed assignment of the complex resonances and resolution of its secondary structure. Evidence is given for a kissing complex fold, which consists of a quasi-continuous helix formed by one stem of DNA, one stem of RNA and a central hybrid helix comprising 5 bp. Two out of helices residues of DNA and one of RNA connect the DNA-RNA loop-loop helix to the stem of either partner in the complex. In addition, two thymines of the DNA stem are engaged in a non-canonical T.T base pair.

Base Pairing↗
PubMedDate not supplied

Thrombocytopenia with absent radii (the TAR syndrome).

The congenital association of thrombocytopenia and absent radii has been designated the TAR syndrome. This article describes a female with the TAR syndrome who presented with the first known onset of hemorrhagic phenomenon at the age of 47, the oldest age of onset described in the literature. The incidence, clinical manifestations, differential diagnosis, course, and effects of treatment of the syndrome are reviewed, and proposed etiologic factors are discussed.

Diagnosis, Differential↗
PubMed2006

Influence of generation 2-5 of PAMAM dendrimer on the inhibition of Tat peptide/ TAR RNA binding in HIV-1 transcription.

The special binding of Tat protein to TAR RNA leads to the transcription of HIV-1 virus. In this study, the influence of 2-5 generation of PAMAM dendrimers on the inhibition of Tat protein/TAR RNA binding has been investigated. The absorption of PAMAM dendrimers on TAR RNA, fixed on a gold substrate through an avidin-biotion connection, was carried out by using a quartz crystal microbalance. Experimental result shows a Langmuir-type isotherm could be used to describe this kind of binding, implying a specific and monolayer adsorption existed. The combination coefficient (K(D)(-1))s can be calculated according to Langmuir Equation, having the order of G3 > G4 > G5 >Tat > G2, indicating that PAMAM G3, G4 and G5 having the possibility to be the inhibitors of HIV-1 transcription. The migration time (T(migra)) of capillary electrophoretic technique has the same sequence as (K(D)(-1))s. These two parameters could be used as simple and quantitative criteria for the selection of possible drugs from numerous candidates for HIV therapy in vitro.

Amino Acid Sequence↗
PubMedDate not supplied

A useful algorithm for calculating central ray TAR and TMR values.

An algorithm utilizing a two-dimensional polynomial power functions least squares fit has been applied to the calculations of TAR in the case of CO-60 teletherapy and TMR in the case of an 8MV LS75/10 linear accelerator giving less than +/- 1/2% errors respectively between calculated and measured values. The TAR and TMR algorithms are used as subroutines in pocket sized and table top programmable calculators or computers and thus provide rapid calculation of treatment time or monitor units as well as given dose.

Cobalt Radioisotopes↗
PubMed1998

Plasmids responsible for horizontal transfer of naphthalene catabolism genes between bacteria at a coal tar-contaminated site are homologous to pDTG1 from pseudomonas putida NCIB 9816-4

The presence of a highly conserved nahAc allele among phylogenetically diverse bacteria carrying naphthalene-catabolic plasmids provided evidence for in situ horizontal gene transfer at a coal tar-contaminated site (J. B. Herrick, K. G. Stuart-Keil, W. C. Ghiorse, and E. L. Madsen, Appl. Environ. Microbiol. 63:2330-2337, 1997). The objective of the present study was to identify and characterize the different-sized naphthalene-catabolic plasmids in order to determine the probable mechanism of horizontal transfer of the nahAc gene in situ. Filter matings between naphthalene-degrading bacterial isolates and their cured progeny revealed that the naphthalene-catabolic plasmids were self-transmissible. Limited interstrain transfer was also found. Analysis of the restriction fragment length polymorphism (RFLP) patterns indicated that catabolic plasmids from 12 site-derived isolates were closely related to each other and to the naphthalene-catabolic plasmid (pDTG1) of Pseudomonas putida NCIB 9816-4, which was isolated decades ago in Bangor, Wales. The similarity among all site-derived naphthalene-catabolic plasmids and pDTG1 was confirmed by using the entire pDTG1 plasmid as a probe in Southern hybridizations. Two distinct but similar naphthalene-catabolic plasmids were retrieved directly from the microbial community indigenous to the contaminated site in a filter mating by using a cured, rifampin-resistant site-derived isolate as the recipient. RFLP patterns and Southern hybridization showed that both of these newly retrieved plasmids, like the isolate-derived plasmids, were closely related to pDTG1. These data indicate that a pDTG1-like plasmid is the mobile genetic element responsible for transferring naphthalene-catabolic genes among bacteria in situ. The pervasiveness and persistence of this naphthalene-catabolic plasmid suggest that it may have played a role in the adaptation of this microbial community to the coal tar contamination at our study site.

Journal Article↗
PubMed1993

The chimeric VirA-tar receptor protein is locked into a highly responsive state.

The wild-type VirA protein is known to be responsive not only to phenolic compounds but also to sugars via the ChvE protein (G. A. Cangelosi, R. G. Ankenbauer, and E. W. Nester, Proc. Natl. Acad. Sci. USA 87:6708-6712, 1990, and N. Shimoda, A. Toyoda-Yamamoto, J. Nagamine, S. Usami, M. Katayama, Y. Sakagami, and Y. Machida, Proc. Natl. Acad. Sci. USA 87:6684-6688, 1990). It is shown here that the mutant VirA(Ser-44, Arg-45) protein and the chimeric VirA-Tar protein are no longer responsive to sugars and the ChvE protein. However, whereas the chimeric VirA-Tar protein was found to be locked in a highly responsive state, the VirA(Ser-44, Arg-45) mutant protein appeared to be locked in a low responsive state. This difference turned out to be important for tumorigenicity of the host strains in virulence assays on Kalanchoë daigremontiana.

Agrobacterium tumefaciens↗
PubMed1993

TAR-independent transactivation of the murine cytomegalovirus major immediate-early promoter by the Tat protein.

Tat is a transactivator of human immunodeficiency virus type 1 (HIV-1) that stimulates gene expression via an RNA target sequence (TAR) by augmenting transcriptional initiation and/or elongation from the HIV-1 long terminal repeat promoter. Here we show that Tat is able to transactivate the murine cytomegalovirus (MCMV) major immediate-early promoter (MIEP), which lacks sequence similarity with the HIV-1 long terminal repeat TAR element. Surprisingly, deletion of the upstream enhancer region (-610 to -146) of the MCMV MIEP abrogated Tat responsiveness. This result suggests that Tat requires a DNA target for function. Quantitation of RNA and protein indicates that Tat stimulates expression from the MCMV MIEP at both the transcriptional and translational levels. Deletion analysis of the MIEP indicates that there is likely to be interplay between the enhancer region, a sequence upstream of the known enhancer which negatively affects expression, and the Tat protein.

Animals↗
PubMed2005

An extremely compensatible cigarette by design: documentary evidence on industry awareness and reactions to the Barclay filter design cheating the tar testing system.

BACKGROUND: The Barclay cigarette (Brown & Williamson) was introduced in 1980 in the USA in the most expensive launch in history. In the USA and around the world, Barclay was later determined to have a grooved filter design that was compromised by human smokers in the normal act of smoking, but that was measured as ultra-low tar using the standard tar testing protocol. OBJECTIVES: To evaluate whether Brown & Williamson knew of the compensatability of Barclay during the design process and before it was released; to evaluate initial responses of competing tobacco companies to Barclay, before complaints were made to the Federal Trade Commission in 1981. METHODS: Internet databases of industry documents (Tobacco Documents Online, Legacy Tobacco Documents Library, Brown & Williamson Litigation discovery website, Guildford and major company websites) were searched using key words, key dates, and targeted searches. Documents related specifically to the development, evaluation and release of the Barclay cigarette and related to the responses by competing tobacco companies were examined. RESULTS: Documents indicate the manufacturer was aware of Barclay design problems and was planning, before release, to respond to criticism. Competing companies quickly detected the filter groove stratagem and considered developing their own similar filter, but eventually backed off. CONCLUSION: The design problems with Barclay were readily understood by cigarette manufacturers, including the maker of Barclay, before official governmental evaluations occurred. Testing involving measured exposures to human smokers may in the end be crucial to identifying problems with novel cigarette designs.

Attitude to Health↗
PubMedDate not supplied

Characterization of TRBP1 and TRBP2. Stable stem-loop structure at the 5' end of TRBP2 mRNA resembles HIV-1 TAR and is not found in its processed pseudogene.

TRBP1 and TRBP2 cDNAs have been isolated based on the ability of the protein that they encode to bind HIV-1 TAR RNA. The two cDNAs have different 5' end-termini resulting in 21 additional amino acids for TRBP2 protein compared to TRBP1. The corresponding gene is conserved in mammalian species. By PCR amplification of a human library, we have isolated an additional 22 nucleotides in the 5' end of TRBP2 cDNA. Based on the addition of these 22 new nucleotides, the first 87 nucleotides of TRBP2 mRNA can fold into a stable stem-loop structure that resembles TAR RNA. We have also isolated the DNA sequence that represents the TRBP processed pseudogene. The absence of full alignment between TRBP2 full-length cDNA and this sequence suggests that the stem-loop structure could have prevented a complete reverse transcription during pseudogene formation. Using different antibodies, three forms of TRBP can be identified in primate cells at 40, 43 and 50 kD, suggesting a differential expression from the cDNAs and post-translational modifications. Both TRBP1 and TRBP2 activate the basal and the Tat-activated level of the HIV-1 LTR in human and murine cells. Our data indicate that TRBP proteins act at a level prior to Tat function. TRBP could contribute to improved HIV expression in murine models.

3T3 Cells↗
PubMed1993

Identification of c-fos-responsive elements downstream of TAR in the long terminal repeat of human immunodeficiency virus type-1.

Activation of HIV-1 requires the binding of host cell transcription factors to cis elements in the proviral long terminal repeat (LTR). This study identifies c-fos-responsive sequence motifs in the U5 transcribed noncoding leader sequences downstream of the viral transactivator responsive (TAR) element. These DNA sequence motifs are the most downstream regulatory elements described thus far in the HIV-1 LTR. Functional studies, using human colon epithelial cell lines, demonstrate that the downstream elements are transactivated by expression of the c-fos protooncogene and can transmit PMA and TNF alpha activation signals to the viral LTR. Moreover, the c-fos-responsive elements mediate HIV-1 LTR transcription independent of Tat and the NF kappa B-binding enhancer element. Nuclear extracts of colon epithelial cells form distinct gel mobility shift complexes with the c-fos-responsive elements. These complexes comigrate with a gel shift complex formed on a classical CRE oligonucleotide and are competed by CRE oligonucleotides. These data indicate that the HIV-1 LTR contains previously unrecognized functional DNA cis-regulatory elements downstream of TAR in the transcribed noncoding 5' leader sequence and suggest that early response genes such as c-fos play a role in the activation of HIV-1 gene expression.

Base Sequence↗
PubMed2006

Progressive nodular histiocytoma associated with thrombocytopenia with absent radii (TAR syndrome) and angiofibromas.

A 50-year-old woman was admitted due to a long-standing history of cutaneous lesions, which were gradually increasing in number and size, located on the trunk and extremities. Histological studies confirmed the initial clinical diagnosis of histiocytomas. Moreover, the patient had numerous smooth erythematous papules on her chin and around her nose, which were diagnosed histologically as angiofibromas. The patient had congenital phocomelia. Analytical and imaging studies revealed the presence of bilateral phocomelia due to absent radii and thrombocytopenia (TAR syndrome). Multiple histiocytomas in a normolipaemic patient bring up several differential diagnoses. Slow progressive evolution without spontaneous resolution and a scattered distribution on the trunk and extremities suggest the diagnosis of progressive nodular histiocytoma. To our knowledge progressive nodular histiocytoma has not been reported previously associated either with TAR syndrome or with angiofibromas. These entities are uncommon, thus their association may not be due to chance.

Angiofibroma↗
PubMedDate not supplied

Management of thrombocytopenia-absent radius (TAR) syndrome.

Thrombocytopenia-absent radius (TAR) syndrome is defined by bilateral absence of the radius and hypomegakaryocytic thrombocytopenia (<150,000/mm3). Lower extremity and nonorthopaedic anomalies also are frequently present. Charts and radiographs of 23 patients with TAR syndrome were reviewed, with extremity and other anomalies documented. Upper and lower extremity management, which included surgery and multiple attempts at orthotic and prosthetic fitting, was evaluated. Upper extremity prostheses were generally rejected, as most patients were able to perform tasks by approximating themselves closely enough to an object to use their own hands. Adaptive devices for feeding, dressing, and toileting were well tolerated. In the lower extremity, most affected patients either rejected any lower extremity intervention or had involvement that eventually precluded functional ambulation, necessitating power wheelchair or motorized cart use. The greatest degree of independence for these patients comes not from surgical, prosthetic, or orthotic intervention, but from the use of simple adaptive devices and powered mobility aids if required.

Child, Preschool↗
PubMed2000

[Studies on shape selective isopropylation products of coal tar naphthalene by gas chromatography/mass spectrometry].

Shape selective isopropylation products of coal tar naphthalene over different zeolite catalysts have been studied by capillary gas chromatography/mass spectrometry (CGC/MS) combined with computerized library search and manual interpretations of mass spectra. The analytical results have shown that products mainly consisted of some monosubstituted, disubstituted and a few trisubstituted naphthalenes. Except the low activity of HZSM-5 catalyst, all other zeolite catalysts have higher activity. HY and H beta catalytic activities were the highest, and their naphthalene conversions attained to 79.12 and 55.79 percent respectively, but their selectivities for 2-isopropylnaphthalene (beta-IPN), 2, 6-diisopropylnaphthalene (2, 6-DIPN) and 2, 7-diisopropylnaphthalene (2, 7-DIPN) were too low. ZM catalysts had good activity and much better selectivity, especially for ZM4-3, of which its 2,6-DIPN/2,7-DIPN ratio was 2.97. Therefore, some zeolite catalysts are recommended for shape selective isopropylation of coal tar naphthalene.

English Abstract↗
PubMed1992

[TAR syndrome (congenital thrombocytopenia and aplasia of the radial bones) in a 5-months-old boy].

A boy aged 5 months had the TAR syndrome (thrombocytopenia and aplasia of radial bones) of autosomal recessive inheritance. Bilateral reduction of the length of the upper extremities included both forearm bones and humerus, so that the shoulder girdle was connected directly to the hand, with all fingers and thumb normally shaped. These skeletal anomalies were associated with thrombocytopenia. Various other abnormalities were present, with the most controversial anomaly being bilateral cleft of the lip and secondary palate. It may be an accidental coexistence of abnormalities or may suggest a common mechanism of the development of the TAR syndrome, Roberts syndrome and SC-phocomelia belonging to hereditary reduction of the extremities with identical mode of inheritance.

Abnormalities, Multiple↗