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F Hill

Publications and source records attributed to F Hill.

At least 37 records · Page 2Linked to original sources
PubMed1999

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗
PubMed1999

Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population.

PURPOSE: To obtain a relationship between background chromosome translocation frequency and age with translocation frequency measured to a high statistical precision, and to identify the role of background ionizing radiation in the production of chromosome translocations in a control population. MATERIALS AND METHODS: Lymphocytes from 35 healthy control individuals (15 females and 20 males) were scored, using fluorescence in situ hybridization, for the presence of chromosomal translocations. Translocation frequencies were measured to a high statistical precision (s.d. 25% or less for each individual). These control subjects were of varying ages, ranging from 0 (cord blood) to 98 years. RESULTS: In a total of 521,492 metaphases (203,754 genome equivalent cells) scored, an average of 5,822 genome equivalent cells per individual, 764 translocations were observed in the 35 individuals. The translocation frequencies ranged from 0 (for cord blood) to 0.0167 (for a 98 year old) translocations per cell. The average age and translocation frequency was 50 years and 0.004 translocations per cell, respectively. The best fit of the relationship between translocations and age was: Y=7x10(-4)+6.9x10(-6)A+1.35x10(-6)A2, which does not obey the linear relationship expected from chronic background radiation alone. The curvilinear relationship observed clearly shows that other endogenous and exogenous clastogens or clastogenic events, in addition to radiation, serve to generate chromosome translocations in control populations. CONCLUSION: The background translocation frequency in control individuals follows a curvilinear relationship with age. No significant variation was observed between individuals of the same age. Clastogenic processes of normal aging and physiological factors in additional to ionizing radiation play a major role in the production of chromosome translocations in a control population. Background radiation, however, appears to play a minor role in chromosome translocation production in control individuals living near sea level.

Adult↗
PubMed1998

The use of tailed octamer primers for cycle sequencing.

Studies have been carried out on the use of octamer oligonucleotides tailed with different base analogues as primers in cycle sequencing reactions. 5-Nitroindole tails improved the performance as primers of a number of octamers. A tail length of three or four 5-nitroindole residues significantly increased the sequencing signal intensity for almost all primers. The use of incomplete libraries of tailed octamer primers for primer walking is discussed.

Base Sequence↗
PubMed1998

In vivo activities of GroEL minichaperones.

Fragments encompassing the apical domain of GroEL, called minichaperones, facilitate the refolding of several proteins in vitro without requiring GroES, ATP, or the cage-like structure of multimeric GroEL. We have identified the smallest minichaperone that is active in vitro in chaperoning the refolding of rhodanese and cyclophilin A: GroEL(193-335). This finding raises the question of whether the minichaperones are active under more stringent conditions in vivo. The smallest minichaperones complement two temperature-sensitive Escherichia coli groEL alleles, EL44 and EL673, at 43 degreesC. Although they cannot replace GroEL in cells in which the chromosomal groEL gene has been deleted by P1 transduction, GroEL(193-335) enhances the colony-forming ability of such cells when limiting amounts of GroEL are expressed from a tightly regulated plasmid. Surprisingly, we found that overexpression of GroEL prevents plaque formation by bacteriophage lambda and inhibits replication of the lambda origin-dependent plasmid, Lorist6. The minichaperones also inhibit Lorist6 replication, but less markedly. The complex quaternary structure of GroEL, its central cavity, and the structural allosteric changes that take place on the binding of nucleotides and GroES are not essential for all of its functions in vivo.

Alleles↗
PubMed1998

Synthesis and RNA polymerase incorporation of the degenerate ribonucleotide analogue rPTP.

The synthesis and enzymatic incorporation into RNA of the hydrogen bond degenerate nucleoside analogue 6-(beta-d-ribofuranosyl)-3, 4-dihydro-8H-pyrimido[4,5-c]-[1,2]oxazin-7-one (P) is described. The 5'-triphosphate of this analogue is readily incorporated by T3, T7 and SP6 RNA polymerases into RNA transcripts, being best incorporated in place of UTP, but also in place of CTP. When all the uridine residues in an HIV-1 TAR RNA transcript are replaced by P the transcript has similar characteristics to the wild-type TAR RNA, as demonstrated by similar melting temperatures and CD spectra. The P-substituted TAR transcript binds to the Tat peptide ADP-1 with only 4-fold lowered efficiency compared with wild-type TAR.

Base Sequence↗
PubMed1998

Polymerase recognition of synthetic oligodeoxyribonucleotides incorporating degenerate pyrimidine and purine bases.

A universal base that is capable of substituting for any of the four natural bases in DNA would be of great utility in both mutagenesis and recombinant DNA experiments. This paper describes the properties of oligonucleotides incorporating two degenerate bases, the pyrimidine base 6H,8H-3,4-dihydropyrimido[4,5-c][1,2]oxazin-7-one and the purine base N6-methoxy-2,6-diaminopurine, designated P and K, respectively. An equimolar mixture of the analogues P and K (called M) acts, in primers, as a universal base. The thermal stability of oligonucleotide duplexes were only slightly reduced when natural bases were replaced by P or K. Templates containing the modified bases were copied by Taq polymerase; P behaved as thymine in 60% of copying events and as cytosine in 40%, whereas K behaved as if it were guanine (13%) or adenine (87%). The dUTPase gene of Caenorhabditis elegans, which we have found to contain three nonidentical homologous repeats, was used as a model system to test the use of these bases in primers for DNA synthesis. A pair of oligodeoxyribonucleotides, each 20 residues long and containing an equimolar mixture of P and K at six positions, primed with high specificity both T7 DNA polymerase in sequencing reactions and Taq polymerase in PCRs; no nonspecific amplification was obtained on genomic DNA of C. elegans. Use of P and K can significantly reduce the complexity of degenerate oligonucleotide mixtures, and when used together, P and K can act as a universal base.

Amino Acid Sequence↗
PubMed1998

Comparative mutagenicities of N6-methoxy-2,6-diaminopurine and N6-methoxyaminopurine 2'-deoxyribonucleosides and their 5'-triphosphates.

The structure of the deoxyribonucleoside derived from N 6-methoxy-2, 6-diaminopurine (dK) was examined by NMR. The methoxyamino residue was found predominantly in the imino rather than the amino tautomer (ratio: 9:1 in DMSO). The nucleoside proved to be a potent transition mutagen in Escherichia coli , in contrast to the closely related nucleoside derived from the analogue N6-methoxyaminopurine (dZ), which was only weakly mutagenic. The 5'-triphosphate derivatives, dKTP and dZTP, were synthesized; Taq polymerase incorporated dKTP opposite both T and, less well, opposite dC in template DNA. Both analogue triphosphates produced transition mutations when added to PCR reactions. In each case, there was a large excess of AT-->GC compared to GC-->AT mutations (ratios were 15:1 for dKTP and 10:1 for dZTP). Polymerase extension times in each cycle had to be extended, consistent with a decreased rate of DNA synthesis in the presence of the analogues. This and the mutagenic ratios are discussed in terms of syn-anti inversion of the methoxyl group.

Aminoimidazole Carboxamide↗
PubMed1998

Improved survival with early intensification: combined results from the Medical Research Council childhood ALL randomised trials, UKALL X and UKALL XI. Medical Research Council Working Party on Childhood Leukaemia.

The Medical Research Council (MRC) United Kingdom trial for childhood acute lymphoblastic leukaemia (UKALL X) randomised patients aged 0-14 years inclusive with an initial white blood count of less than 100 x 10(9)/l to receive an early intensification block, a late intensification block, both, or neither. The next trial, UKALL XI, for children aged 1-14 years, randomised between different central nervous system (CNS) directed therapies. At the beginning of the trial, all patients were also randomised between late intensification alone and both early plus late blocks. The effects of both the early and the late block in UKALL X alone have been reported previously. This paper examines the effect of the addition of the early intensification block to treatment which included late intensification, combining the data from UKALL X and the first part of UKALL XI. Early intensification was associated with fewer bone marrow relapses and a reduction in the odds of death of 0.63 (95% confidence interval: 0.46-0.87). Survival was significantly improved with an increase at 5 years of 8%, from 79 to 87%. Following this demonstration that early intensification improves survival, the effect of a third intensification block is under investigation.

Adolescent↗
PubMed1998

Food mail: the Canadian alternative to food stamps.

PURPOSE: To describe the impact of a selective transportation subsidy on food costs in isolated communities in Northern Canada, and the government's proposal to refine the "food mail" program to promote better nutrition. METHOD: The cost of various components of a Northern Food Basket has been monitored since 1990. An assessment of the probable impact and acceptability of program refinements was made through surveys of merchants and health and social service providers and focus group sessions. Decisions expected following consultations with stakeholders in March and April 1996 are also described. RESULTS: Costs of nutritious perishable food have been reduced in the Northwest Territories, and consumption of these foods in the Baffin region doubled within three years. Program refinements were proposed, with the objective of increasing intakes of calcium, folacin, and vitamin A, reducing dependency on convenience perishable foods, and reducing the cost of a healthy diet.

Arctic Regions↗
PubMed1998

Food affordability in air stage communities.

In 1991 and 1992, changes were made to the rate structure and eligibility requirements of the Northern Air Stage Program. To determine the effect of these changes on the affordability of a nutritious diet, food price surveys were conducted in 20 isolated communities, staging points, and selected southern cities and used to cost a 46-item Northern Nutritious Food Basket (NFB), which meets the nutrient requirements of a reference family of four. Food affordability was calculated as the percentage of "after-shelter" social assistance income required to purchase the NFB. In the Northwest Territories (NWT), from 100% to 123% of income was required in Air Stage communities in 1990-1991 and from 86% to 125% in 1993. In the provinces, from 65% to 83% of income was needed in 1990-1991 and from 56% to 98% in 1993. In Kangiqsujuaq and Nain, the amount of "after-shelter" income needed increased by as much as 6% and 15%, respectively. Changes to the Northern Air Stage Program reduced the cost of perishable foods and improved the affordability of a nutritious diet in the NWT. Affordability is also affected by social assistance income. In most isolated communities, families would still find it difficult to afford a nutritious diet.

Adolescent↗
PubMed1998

Food consumption patterns of Inuit women.

To evaluate nutrient intake and food consumption patterns of Inuit women of child-bearing age, a 24-hour diet recall and general health and food frequency questionnaire was administered to 688 Inuit women aged 15-44 in six isolated communities. Data were analyzed using the 1991 Canadian Nutrient File. Mean intakes of essential nutrients were expressed as percentages of Health Canada's 1990 Recommended Nutrient Intakes (RNI). Chi-square tests were used to determine relationships between categorical variables. Folacin intake ranged from 49% to 95% of the RNI in most communities (median = 76%) and was only 37% of the RNI for pregnant and 54% for lactating women. Mean calcium intake for pregnant and lactating women averaged 55% and 47% of the RNI, respectively. Average vitamin A intakes ranged from 26% to 87% of the RNI (median = 65%), with intake for pregnant Inuit women and lactating women 79% and 54% of the RNI, respectively. Country food was the major source of protein and iron, and store foods the major source of calories, calcium, folacin, and vitamin A. Low intakes of folacin, calcium, and vitamin A, especially among pregnant and lactating women, place Inuit women of childbearing age at risk. Women on social assistance are nutritionally vulnerable.

Adolescent↗
PubMed1997

Stability and structure of DNA oligonucleotides containing non-specific base analogues.

The nature of DNA containing the deoxyribosyl derivative of 5-nitroindole has been investigated. 5-Nitroindole has been shown to give good stability when present in duplexes opposite natural bases, with only slightly reduced melting temperatures. However, enhanced stability occurs when it is incorporated as an additional bulged base in duplexes. It also markedly enhances the stability of duplexes when it is present as a pendant base at either the 5' or 3'-ends of the two strands. The stabilisation is presumed to be due to enhanced stacking interactions for the nitroindole base. Oligomers containing a number of consecutive 5-nitroindole residues form stable, stacked secondary structures. An oligomer containing 21 such substitutions is presumed to exist as a hairpin structure. This was further investigated by circular dichroism melting experiments, which demonstrated that the single-stranded oligomer contains significant secondary structure in the region of the 5-nitroindole tract, which appears to contain a double-stranded stem. X-ray analysis of 5-nitroindole deoxyriboside provides some indication of how the mode of stacking observed in crystals of the nucleoside may also be responsible for stabilising secondary structures of oligonucleotides.

Base Sequence↗
PubMed1997

An ageing-associated decline in force production after repetitive contractions by rat skinned skeletal muscle fibres.

Chemically skinned muscle fibre segments were prepared from the extensor digitorum longus (EDL) and soleus muscles of young (5-6 months) and old (24-31 months) male Wistar rats. Muscle fibres were activated repetitively with a buffered calcium solution a total of 50 times, and the force resulting from each activation recorded. Both EDL and soleus fibres showed a substantial decline in maximum force over the series of 50 contractions. The decline in maximum force was significantly higher in old EDL and soleus fibres than in their young counterparts, indicating a difference between the contractile apparatus of skeletal muscle from young and old animals. Normalized tension, defined as force per muscle fibre cross-sectional area, was significantly lower in fibres from the old animals than from the young, giving further evidence of the existence of changes to the contractile apparatus with ageing.

Aging↗
PubMed1996

cec-1, a soma-specific chromobox-containing gene in C. elegans.

The chromo domain is a phylogenetically conserved sequence motif which was identified as a region of homology between the repressor protein Pc and the heterochromatin constitutive protein HP1 of Drosophila. The specific function of the chromo domain is not yet understood, but it seems to be required for protein-protein interactions in chromatin-associated complexes. Here, we present a new chromobox-containing gene from Caenorhabditis elegans (cec-1). It encodes a nuclear protein that is present in all somatic cells from the 50- to 80-cell stage on throughout development and in adult animals. No cec-1 protein was detected in the cells of early embryos, in germ cells, and in their precursor cells Z2 and Z3. cec-1 mRNA, however, is already present in all the blastomeres of early embryos. Immunolocalization experiments revealed a homogeneous distribution of CEC-1 within interphase nuclei, while during mitosis CEC-1 seems to dissociate from the condensing chromosomes. The expression pattern of the cec-1 gene suggests that it may represent a new regulatory gene in C. elegans.

Amino Acid Sequence↗
PubMed1996

The Global Oscillation Network Group (GONG) Project

Helioseismology requires nearly continuous observations of the oscillations of the solar surface for long periods of time in order to obtain precise measurements of the sun's normal modes of oscillation. The GONG project acquires velocity images from a network of six identical instruments distributed around the world. The GONG network began full operation in October 1995. It has achieved a duty cycle of 89 percent and reduced the magnitude of spectral artifacts by a factor of 280 in power, compared with single-site observations. The instrumental noise is less than the observed solar background.

Journal Article↗
PubMed1996

The Current State of Solar Modeling

Data from the Global Oscillation Network Group (GONG) project and other helioseismic experiments provide a test for models of stellar interiors and for the thermodynamic and radiative properties, on which the models depend, of matter under the extreme conditions found in the sun. Current models are in agreement with the helioseismic inferences, which suggests, for example, that the disagreement between the predicted and observed fluxes of neutrinos from the sun is not caused by errors in the models. However, the GONG data reveal subtle errors in the models, such as an excess in sound speed just beneath the convection zone. These discrepancies indicate effects that have so far not been correctly accounted for; for example, it is plausible that the sound-speed differences reflect weak mixing in stellar interiors, of potential importance to the overall evolution of stars and ultimately to estimates of the age of the galaxy based on stellar evolution calculations.

Journal Article↗
PubMed1996

The Solar Acoustic Spectrum and Eigenmode Parameters

The Global Oscillation Network Group (GONG) project estimates the frequencies, amplitudes, and linewidths of more than 250,000 acoustic resonances of the sun from data sets lasting 36 days. The frequency resolution of a single data set is 0.321 microhertz. For frequencies averaged over the azimuthal order m, the median formal error is 0.044 microhertz, and the associated median fractional error is 1.6 x 10(-5). For a 3-year data set, the fractional error is expected to be 3 x 10(-6). The GONG m-averaged frequency measurements differ from other helioseismic data sets by 0.03 to 0.08 microhertz. The differences arise from a combination of systematic errors, random errors, and possible changes in solar structure.

Journal Article↗