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T Dale

Publications and source records attributed to T Dale.

15 recordsLinked to original sources
PubMed2001

Modifying the specificity of an RNA backbone contact.

The interaction between the MS2 bacteriophage coat protein homodimer and its cognate RNA hairpin is facilitated by 21 different RNA-protein contacts. In one of these contacts, the 2'-hydroxyl group at ribose -5 of the RNA acts as a hydrogen bond donor to Glu63 in one subunit of the protein. Previous experiments showed that substitution of ribose -5 with deoxyribose resulted in a 24-fold decrease in binding affinity between RNA and protein. Using a protein where the two MS2 monomers were fused to increase stability, the contribution of this contact to the overall binding affinity was investigated by site-directed mutagenesis. When Glu63 was substituted with glutamine, aspartate, or alanine, the binding affinity of the hairpin for the protein was weakened by 12 to 100-fold, similar to that observed with deoxyribose at position -5. However, the specificity of the three mutant proteins for RNAs with various modifications at the 2'-position of ribose -5 differed dramatically. While the Glu63Asp protein resembled the wild-type protein in preferring the 2'-hydroxyl group over a proton or a bulky 2'-substituent, both the Glu63Ala and Glu63Gln proteins preferred bulky 2'-substituents over the 2'-hydroxyl group by more than 100-fold. These experiments emphasize the ease with which the specificity of a protein-nucleic acid interaction can be changed at thermodynamically important sites.

Binding Sites↗
PubMed2001

Accurate case finding using linked electronic clinical and administrative data at a children's hospital.

To link hospital administrative data and an electronic medical record at a children's hospital in order to identify children with cancer admitted for fever and neutropenia. Hospital administrative data concerning 13,374 inpatient and outpatient encounters were validated against and linked to clinical data stored in an electronic medical record. Queries of the linked databases identified children with fever and neutropenia. Sensitivity and specificity of the experimental case-finding strategy were determined and compared to a control case-finding strategy utilizing administrative data alone. Linking of the clinical record to the administrative record was achieved in 233 (99%) of the 235 records. Of 1680 data elements reviewed from the administrative data that were also potentially available in the clinical data system, 1679 (99.9%) were verified in the electronic medical record. The experimental strategy for case finding had a sensitivity of 73.1% (95% CI: 58.1, 88.3), specificity 99.6% (95% CI: 99.1, 100). If only administrative data such as diagnosis-related group and hospital service were used for case finding, both the sensitivity (P < 0.01) and specificity (P < 0.01) were significantly lower. Linking a children's hospital administrative data system with clinical data is feasible and can be utilized for specific case finding for a common and costly condition in children.

Child↗
PubMed2001

tRNA conformity.

Explore the source record for details and available documents.

Amino Acid Sequence↗
PubMed2000

Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development.

Interactions between the Wnt (wingless) and hedgehog signaling pathways were first described as playing a role in establishing boundaries between ectodermal cells in Drosophila segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm must be formed to correctly position the sites of tooth formation. We describe a reciprocal relationship between the expression of Wnt-7b in presumptive oral ectoderm and Shh in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates. By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down-regulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repress Shh expression in oral ectoderm, thus maintaining the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt-7b specifically affects Shh signaling.

Animals↗
PubMed2000

A test of the model to predict unusually stable RNA hairpin loop stability.

To investigate the accuracy of a model [Giese et al., 1998, Biochemistry37:1094-1100 and Mathews et al., 1999, JMol Biol 288:911-940] that predicts the stability of RNA hairpin loops, optical melting studies were conducted on sets of hairpins previously determined to have unusually stable thermodynamic parameters. Included were the tetraloops GNRA and UNCG (where N is any nucleotide and R is a purine), hexaloops with UU first mismatches, and the hairpin loop of the iron responsive element, CAGUGC. The experimental values for the GNRA loops are in excellent agreement (deltaG degrees 37 within 0.2 kcal/mol and melting temperature (TM) within 4 degrees C) with the values predicted by the model. When the UNCG hairpin loops are treated as tetraloops, and a bonus of 0.8 kcal/mol included in the prediction to account for the extra stable first mismatch (UG), the measured and predicted values are also in good agreement (deltaG degrees 37 within 0.7 kcal/mol and TM within 3 degrees C). Six hairpins with unusually stable UU first mismatches also gave good agreement with the predictions (deltaG degrees 37 within 0.5 kcal/mol and TM within 8 degrees C), except for hairpins closed by wobble base pairs. For these hairpins, exclusion of the additional stabilization term for UU first mismatches improved the prediction (AG degrees 37 within 0.1 kcal/mol and TM within 3 degrees C). Hairpins with the iron-responsive element loop were not predicted well by the model, as measured deltaG degrees 37 values were at least 1 kcal/mol greater than predicted.

Base Pair Mismatch↗
PubMed1998

Stability of RNA hairpins closed by wobble base pairs.

Thermodynamic parameters are reported for hairpin formation in 1 M NaCl by RNA sequences of the type GGXANmAYCC, where XY is the wobble base pair, GU or UG, and the underlined loop sequences are three to eight nucleotides. A nearest-neighbor analysis indicates the free energy of loop formation is dependent upon loop size and closing base pair. Hairpin loops closed by UG base pairs are on average 1.3 kcal/mol less stable than hairpins closed by GU base pairs. The hairpin loops closed by UG have approximately the same stability as hairpin loops closed by AU/UA base pairs, while the loops closed by GU are approximately 0.7 kcal/mol more stable than hairpins loops closed by GC/CG base pairs. These results, combined with the model previously developed [Serra et al. (1997) Biochemistry 36, 4844] to predict the stability for hairpin loops closed by Watson-Crick base pairs, allow for the following model to predict the stability of hairpin loops: delta G degree 37L(n) = delta G degree 37iL(n) + delta G degree 37mm + 0.6 (if closed by AU, UA, or UB) - 0.7 (if closed by GU) - 0.7 (if first mismatch is GA or UU except for loops closed by GU). Here, delta G degree 37iL(n) is the free energy increment for initiating a loop of n nucleotides with a CG or GC pair, and delta G degree 37mm is the free energy for the interaction of the first mismatch with the closing base pair. For hairpin loops of n = 4-9, delta G037iL(n) is 4.9, 5.0, 5.0, 5.0, 4.9, and 5.5 kcal/mol, respectively. For hairpin loops of n = 3, delta G degree 37L(3) = +4.8 + 0.6 (if closed by AU, UA, or UG) kcal/mol. Thermodynamic parameters for hairpin formation in 1 M NaCl for 13 naturally occurring RNA hairpin sequences closed by wobble base pairs are reported. The model provides good agreement for both TM and delta G degree 37 for most hairpins studied. Thermodynamic values for five terminal mismatches adjacent to wobble base pairs are also reported.

Base Composition↗
PubMed1995

HGF/SF: a potent cytokine for mammary growth, morphogenesis and development.

The mammary gland is a renewing tissue in which morphogenetic processes and differentiation occur cyclically during the menstrual cycle, pregnancy and lactation. These events have been shown to be dependent upon epithelial-mesenchymal interactions. Studies of the effects of individual factors, their cellular source and their target cell populations in the different developmental stages of the mammary gland are greatly facilitated by the accessibility of this organ and the application of new techniques that allow purification of the major epithelial and stromal components of this tissue. Here we demonstrate that HGF/SF and its cellular receptor, c-met, are expressed and regulated temporally during mouse mammary development and differentiation. We show that human and mouse mammary fibroblasts produce HGF/SF and that HGF/SF is not only mitogenic but morphogenic and motogenic for both human and mouse mammary epithelial cells. We have found that human luminal and myoepithelial cells express c-met differentially and that HGF/SF has different effects on these two mammary epithelial cell populations. HGF/SF is mitogenic for luminal cells but not myoepithelial cells, and morphogenic to myoepithelial cells but not luminal cells. This is discussed in the context of the proliferative compartments in the normal mammary gland and the potential role of the myoepithelial cells to act as the skeleton for ductal development.

Animals↗
PubMed1993

Anti-emetic profile of a non-peptide neurokinin NK1 receptor antagonist, CP-99,994, in ferrets.

In the ferret, 5-HT3 receptor antagonists are effective in controlling emesis produced by cytotoxic agents or radiation. To investigate the possibility that substance P has a role, as well as 5-HT, in the emetic reflex pathway, we have examined the anti-emetic effects of a NK1 receptor antagonist (racemic CP-99,994) in the ferret. Racemic CP-99,994 was effective against a range of emetogens, comprising cytotoxic drugs, radiation, morphine, ipecacuanha and copper sulphate.

Animals↗
PubMed1991

[Anesthetic gases, the ozone layer and the greenhouse effect. How harmful are the anesthetic emissions for the global environment?].

During the last decade, world society has acknowledged the harmful effects on the environment of the greenhouse effect and of depletion of the ozone layer, caused by industrial emissions of man-made compounds. Ozone depletion is caused mainly by chlorine compounds or nitrogen oxides released by degradation in the stratosphere. The greenhouse effect is caused by increased trapping of terrestrial heat radiation. Degradation of the anaesthetic vapours halothane, enflurane and isoflurane releases chlorine, and nitrous oxide degradation produces reactive nitrogen oxides. Nitrous oxide in particular, but also the vapours, absorb terrestrial radiation. The total discharge of anaesthetic vapours contributes to less than 0.01% of the total atmospheric chlorine load, and the annual Norwegian release of approximately two tons accounts for 0.2% of the world total. It is estimated that the total amount of nitrous oxide released from anaesthetics accounts for 0.05% of the greenhouse effect, while annual Norwegian emissions of nitrous oxide (less than 160 tons) comprise 0.2-0.4% of world total. Because of their favourable clinical properties and their modest contribution to ozone depletion and the greenhouse effect, medical use of inhalational anaesthetic agents should not be banned. However, low flow anaesthetic techniques should be employed, in order to reduce their negative impacts on the atmosphere.

Air Pollutants↗
PubMedDate not supplied

A transcription factor which binds to the enhancers of SV40, immunoglobulin heavy chain and U2 snRNA genes.

In eukaryotes the transcriptional control of RNA polymerase II-mediated gene expression is exerted by cis-acting regulatory DNA elements classified as promoter and enhancer sequences. These elements are composed of a number of different protein binding sites. The regulatory factors that recognize such 'modules' may be ubiquitous, tissue- or stage-specific, and positively or negatively acting. According to this model the transcriptional activity of a given gene is programmed by a combination of different modules. We analysed such a site of protein-DNA interaction, the octamer motif, in the enhancers of the simian virus (SV40) early genes and the murine immunoglobulin heavy-chain gene, and in the distal sequence element (DSE) of the U2 small nuclear (sn)RNA gene of Xenopus laevis. The corresponding DNA-binding factor appears to be the same in the three cases. Moreover, a fraction containing partially purified octamer motif binding factor has a stimulatory effect on transcription in an in vitro system.

Animals↗
PubMedDate not supplied

Sexual behavior, communication, and chlamydial infections among college women.

The sexual practices, partner communication patterns, and prevalence of chlamydial infection were determined in a sample of college women. Specific inclusion criteria were used to screen 146 participants. The presence of a mucopurulent cervical discharge was the only criterion significantly associated with infection. Only 12% of the sample used condoms alone or in combination with another birth control method, and only 31% of the women discussed with their partner their own or their partner's sexual history. Thirty-eight percent of the sample reported a history of one to four episodes of a sexually transmitted disease, and 21% of the women stated they had had two or more sexual partners within the past 6 months. Health providers, counselors, and women themselves must address this health issue with more assertive behavior and communication skills.

Adolescent↗