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D H Hall

Publications and source records attributed to D H Hall.

At least 37 records · Page 2Linked to original sources
PubMed1997

Retinal ischemia leads to apoptosis which is ameliorated by aurintricarboxylic acid.

Transient retinal ischemia results in a delayed cell death of the inner retinal layers. This study demonstrates that this ischemic cell death occurs, at least in part, through apoptosis. The general endonuclease inhibitor, aurintricarboxylic acid, protected rat retinal cells from ischemic cell damage when administered before the onset of ischemia and, more importantly, when administered 6 hr after the insult. Thus, the demonstration that transient retinal ischemia results in cell damage as a result of apoptosis opens new therapeutic strategies aimed at lessening retinal damage as a result of this process.

Animals↗
PubMed1995

The mab-21 gene of Caenorhabditis elegans encodes a novel protein required for choice of alternate cell fates.

The gene mab-21, which encodes a novel protein of 386 amino acids, is required for the choice of alternate cell fates by several cells in the C. elegans male tail. Three cells descended from the ray 6 precursor cell adopt fates of anterior homologs, and a fourth, lineally unrelated hypodermal cell is transformed into a neuroblast. The affected cells lie together in the lateral tail epidermis, suggesting that mab-21 acts as part of a short-range pattern-formation mechanism. Each of the changes in cell fate brought about by mab-21 mutants can be interpreted as a posterior-to-anterior homeotic transformation. mab-21 mutant males and hermaphrodites have additional pleiotropic phenotypes affecting movement, body shape and fecundity, indicating that mab-21 has functions outside the tail region of males. We show that the three known alleles of mab-21 are hypomorphs of a new gene. Mosaic analysis revealed that mab-21 acts cell autonomously to specify the properties of the sensory ray, but non-autonomously in the hypodermal versus neuroblast cell fate choice. Presence of cell signalling in the choice of the neuroblast fate was confirmed by cell ablation experiments. Mutations in mab-21 were shown previously to be genetic modifiers of the effects of HOM-C/Hox gene mutations on ray identity specification. The results presented here support the conclusion that mab-21 acts as part of a mechanism required for correct cell fate choice, possibly involving the function of HOM-C/Hox genes in several body regions.

Alleles↗
PubMed1994

A non-directed, hydroxylamine-generated suppressor mutation in the P3 pairing region of the bacteriophage T4 td intron partially restores self-splicing capability.

Hydroxylamine (HA) mutagenesis of an HA-induced splicing-defective bacteriophage T4 td intron mutant with a mutation in the intron P3 RNA pairing region was used to generate pseudorevertants. Because HA can only cause GC to AT transitions, the original mutant (H104A) could not undergo true reversion, yet the compensatory mutation on the opposite side of the P3 helix, which was complementary to the original H104A mutation, could occur. A pseudorevertant was isolated that contained both the original H104A mutation and the compensatory mutation HS9. By phenotypic and molecular genetic criteria, this double mutant (H104A-HS9) was shown to be able to undergo significant RNA splicing, thus confirming the existence and functional importance of the long-range P3 pairing region in this phage intron. The second-site suppressor mutation (HS9) was isolated by phage cross and also exhibited some self-splicing ability. A correlation exists between the strength of P3 helix Watson-Crick base pairing and the apparent level of splicing when wild-type, H104A, HS9, and H104A-HS9 are compared. This suggests that the primary role of the P3 RNA pairing region in the T4 td intron is structural in contributing to the critical RNA secondary structure.

Aged↗
PubMed1993

A novel approach for isolation and mapping of intron mutations in a ribonucleotide reductase encoding gene (nrdB) of bacteriophage T4 using the white halo plaque phenotype.

The nrdB gene of bacteriophage T4 codes for the small subunit of ribonucleotide reductase and contains a 598 base pair self splicing intron which is closely related to other group I introns of T4 and eukaryotes. The screening, isolation and mapping of the nrbB intron mutations was conducted by the strategic usage of the white halo phenotype exhibited by T4 mutants defective in dhydrofolate reductase or thymidylate synthase. We have isolated 159 hydroxylamine-induced nrdB mutants, determined which mutations are in nrdB by marker rescue with clones of the nrdB gene and have mapped these mutations by marker rescue using subclones of the nrdB intron. Thirty out of the 159 nrdB mutations are in or near the intron. These mutations cluster towards the ends, mainly the 3' end. We have performed deletion mapping to further map mutations in the 3' end of the intron. The mutations map in regions of conserved structural elements, thus supporting secondary structure predictions similar to those of the well studied td intron in the T4 gene coding for thymidylate synthase.

Bacteriophage T4↗
PubMed1993

Distribution and characterization of mutations induced by nitrous acid or hydroxylamine in the intron-containing thymidylate synthase gene of bacteriophage T4.

The detailed distribution and characterization of 51 hydroxylamine (HA)-induced and 59 nitrous acid (NA)-induced mutations in the intron-containing bacteriophage T4 thymidylate synthase (td) gene is reported here. Mutations were mapped in 10 regions of the td gene by recombinational marker rescue using plasmid or M13 subclones of the td gene. Phage crosses using deletion mutants with known breakpoints in the 3' end of the td intron subdivided HA and NA mutations which mapped in this region. At least 31 of the mutations map within the 1-kb group I self-splicing intron. Intron mutations mapped only in the 5' and 3' ends of the intron sequence, in accordance with the hypothesis that the 5' and 3' domains of the T4 td intron are essential for correct RNA splicing. RNA sequence analysis of a number of mapped td mutations has identified two intron nucleotides and one exon nucleotide where both HA- and NA-induced mutations commonly occur. These three loci are characterized by a GC dinucleotide, with the mutations occurring at the cytosine residue. Thus, these data indicate at least three potential sites of both HA- and NA-induced mutagenic hotspot activity within the td gene.

Bacteriophage T4↗
PubMed1993

A proflavin-induced frameshift hotspot in the thymidylate synthase gene of bacteriophage T4.

Twenty-one independent thymidylate synthase deficient (td) mutants were isolated after proflavin mutagenesis of T4D0 phage. A strikingly high proportion of these mutations (17 of 21; 80%) mapped in a small 122 nucleotide (nt) region which spans the 5' splice site of this intron-containing gene. This region comprises only 14% of the total td exon sequence. RNA sequence analysis of these mutants identified a series of frameshift insertion/deletion mutations and indicated a hotspot for proflavin-induced mutations in the 3' end of exon I of the td gene. The mutant sequences at the hotspot site fully support a previously proposed mutagenic mechanism for proflavin-induced mutations in which frameshifts are produced as a consequence of exonuclease or DNA polymerase activity at the 3' ends of nicks in the DNA produced by perturbation of the T4-encoded type II topoisomerase activity by the acridine. Sixteen of the seventeen DNA mutations in the hotspot region can be explained by the model as a consequence of enzymatic processing of nicks at two phosphodiester bonds staggered by 4 base pairs (bp) and located on opposite strands of the DNA. Thus, these mutants exhibit precisely the symmetry expected of topoisomerase-mediated mutagenesis. The DNA sequences of the td hotspot mutants, when considered with the sequences of proflavin-induced mutants in the T4 rIIB and lysozyme genes, confirm the view that proflavin-induced mutations in diverse bacteriophage T4 DNA sequences are all produced by the topoisomerase-dependent mechanisms and do not support the view that classical misalignments in DNA repeats are hotspots for proflavin-induced mutagenesis in T4.

Bacteriophage T4↗
PubMed1993

Cytokine-induced programmed death of cultured sympathetic neurons.

Programmed cell death (PCD) of sympathetic neurons is inhibited by nerve growth factor. However, factors that induce PCD of these cells are unknown. Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor, neuropoietic cytokines known to regulate sympathetic neuron gene expression, were examined for effects on survival of cultured sympathetic neurons. Treatment with LIF or ciliary neurotrophic factor caused neuronal death in a dose-dependent fashion. Inhibition of RNA or protein synthesis, or treatment with potassium, all of which prevent PCD after nerve growth factor deprivation, prevented LIF-induced death. The morphologic and ultrastructural characteristics of the neuronal death induced by LIF and by nerve growth factor deprivation were similar. Furthermore, LIF treatment resulted in DNA fragmentation with a characteristic "ladder" on Southern blot analysis. These observations suggest that neuron numbers may be regulated by factors which initiate PCD, as well as by factors which prevent it.

Analysis of Variance↗
PubMed1993

Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans.

Six touch receptor neurons with distinctive morphological features sense gentle touch in Caenorhabditis elegans. Previous studies have identified three genes (lin-32, unc-86 and mec-3) that regulate touch cell development. However, since other cell types also require these genes, we suspected that other genes help restrict the expression of touch cell characteristics to the six neurons seen in the wild type. To identify such genes, we have examined mutants defective in genes required for the development of other C. elegans cells for changes in the pattern of touch cell-specific features. Mutations in seven genes either reduce (lin-14) or increase (lin-4, egl-44, egl-46, sem-4, ced-3 and ced-4) the number of touch receptor-like cells. The combinatorial action of these genes, all of which are required for the production of many cell types, restrict the number of cells expressing touch receptor characteristics in wild-type animals by acting as positive and negative regulators and by removing cells by programmed cell death.

Animals↗
PubMed1992

Comparison of Identification Systems for Classification of Bacteria Isolated from Water and Endolithic Habitats within the Deep Subsurface.

One water and three rock samples were taken from a mined tunnel system, U12n, in Rainier Mesa at the Nevada Test Site. Endolithic microorganisms were cultured from ashfall tuff, which was crushed and made into slurries with a formulation of artificial pore water, on R2A agar plates. Microbial counts ranged from 10 to 10 viable cells per g (dry weight) of rock sampled. The cultured water sample yielded 10 viable cells per ml. Many of the isolates were very small (<1 mum) when viewed in the rock matrix and remained small even when cultured. Most were gram-negative rods. Individual isolates were profiled by API-NFT strip number, antibiotic and metal resistance patterns, and colony and cellular morphologies. Three identification systems, API-NFT strips, BIOLOG, and MIDI, were compared. Each system identified only a small percentage of the total isolates, and in only seven cases were the isolates identified the same way by more than one system. The same genus was identified in three of these cases, but different species were indicated. The genus Pseudomonas was the most commonly identified. The isolate profiles and the three identification systems demonstrated that water isolates were considerably different from endolithic isolates.

Journal Article↗
PubMed1991

Kinesin-related gene unc-104 is required for axonal transport of synaptic vesicles in C. elegans.

unc-104 encodes a novel kinesin paralog that may act as a microtubule-based motor in the nervous system. Neuronal cell lineages and axonogenesis are normal in unc-104 null mutants, but axons have few synaptic vesicles and make only a few small synapses. By contrast, neuron cell bodies have surfeits of similar vesicles tethered together within the cytoplasm. Based on behavioral and cellular phenotypes, we suggest that UNC-104 is a neuron-specific motor used for anterograde translocation of synaptic vesicles along axonal microtubules. Other membrane-bounded organelles are transported normally.

Adenosine Triphosphatases↗
PubMed1991

Motor vesicles.

Explore the source record for details and available documents.

Journal Article↗
PubMed1991

The posterior nervous system of the nematode Caenorhabditis elegans: serial reconstruction of identified neurons and complete pattern of synaptic interactions.

Serial-section electron microscopy has been used to reconstruct the cellular architecture of the posterior nervous system of the nematode Caenorhabditis elegans. Each of 40 neurons in the tail of the adult hermaphrodite can be reproducibly and unambiguously identified by a set of morphological features, including cell body position, fiber geometry and size, and staining properties. A complete list of synapses has been assembled for 2 isogenic animals, and these lists are compared with a third isogenic animal reconstructed by White et al. (1986). The set of neurons and their pattern of synaptic interactions is simple and reproducible. Most of the cells are involved in sensory transduction or in local signal processing to relay signals via a few interneurons to motoneurons and thence to body muscles. Because the tail neurons are well separated and fairly reproducible in position, the hermaphrodite tail lends itself to laser-ablation studies of sensory processing (cf. Chalfie et al., 1985). Most of the synapses in the tail are concentrated in the preanal ganglion. Among the approximately 150 synapses there, about 85% are dyadic chemical synapses. The dyadic synapses are involved in reproducible patterns that have several interesting features. Most neurons synapse onto a few preferred pairs of target cells, in patterns that suggest a combinatorial model of synapse specification that may be open to genetic analysis. Furthermore, most dyadic contacts A----B,C fit a pattern in which the 2 postsynaptic partners are involved elsewhere in unidirectional synapses B----C. Thus, the dyadic synapse may serve to diverge sensory signals into parallel pathways, which then reconverge. This divergence/reconvergence pattern eventually directs processed sensory signals to the ventral cord interneurons PVCL and PVCR. About 80-90% of the synapses fall into repeated classes of synapses. Many of the remaining synapses are widely scattered and irreproducible from one animal to the next. Some of these contacts may be developmental mistakes reflecting a degree of "noise" in synapse specification (Waddington, 1957).

Animals↗
PubMed1990

The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans.

Three known genes guide circumferential migrations of pioneer axons and mesodermal cells on the nematode body wall. unc-5 affects dorsal migrations, unc-40 primarily affects ventral migrations, and unc-6 affects migrations in both directions. Circumferential movements still occur, but are misdirected whereas longitudinal movements are normal in these mutants. Pioneer growth cones migrating directly on the epidermis are affected; growth cones migrating along established axon fascicles are normal. Thus these genes affect cell guidance and not cell motility per se. We propose that two opposite, adhesive gradients guide circumferential migrations on the epidermis. unc-5, unc-6, and unc-40 may encode these adhesion molecules or their cellular receptors. Neurons have access to the basal lamina and the basolateral surfaces of the epidermis, but mesodermal cells contact only the basal lamina. These genes probably identify molecular cues on the basal lamina that guide mesodermal migrations. The same basal lamina cues, or perhaps related molecules on the epidermal cell surfaces, guide pioneer neurons.

Animals↗
PubMed1989

Sequence specificity of the P6 pairing for splicing of the group I td intron of phage T4.

Seventeen non-directed td- (thymidylate synthase-deficient) splicing-defective mutations isolated in phage T4 were localized within the catalytic core of the ribozyme. All of the mutations occur in conserved structural elements that form part of the td intron core secondary structure. Remarkably, seven of the seventeen independently isolated mutations clustered in the dinucleotide 5' element (P6[5']) of the putative two-base-pair P6 stem. An analysis of this region was undertaken by site-directed mutagenesis of the plasmid-borne td gene, leading to the following findings: First, the short P6 pairing in the td secondary structure model was verified with appropriate P6[5'] and P6[3'] compensatory mutations. Second, all P6[5'] and P6[3'] mutants are defective in the first step of splicing, guanosine-dependent 5' splice site cleavage, whereas their activity at the 3' splice site is variable. Third, residual in vitro splicing activity of the mutants altered on only one side of the P6 pairing is correlated with the ability to form an alternative two-base-pair P6 stem. Fourth, the degree to which the compensatory mutants have their splicing activity restored is highly condition-dependent. Restoration of phenotype of the compensatory P6[5']:[3'] constructs is weak under stringent in vitro conditions as well as in vivo. This sequence specificity is consistent with phylogenetic conservation of the P6 pairing elements in group I introns, and suggests either structural constraints on the P6 stem or a dual function of one or both pairing elements.

Base Composition↗
PubMed1989

Exon shuffling by recombination between self-splicing introns of bacteriophage T4.

The organization of genes into exons separated by introns may permit rapid evolution of protein-coding sequences by exon shuffling. Introns could provide non-coding targets for recombination, which would then give rise to novel combinations of exons. Evidence to support this theory is indirect and consists of examples of homologous domains of protein structure encoded in different genes, with introns in conserved positions at the boundaries of these domains. Here, we report the first direct evidence for exon shuffling. Two spontaneous deletion mutations of phage T4 have been characterized by sequencing, and they are clearly the result of recombination between homologous regions of two self-splicing group I introns. As a result of the recombination, exons of different genes are transcribed together, with a hybrid intron between them. One of these introns is proficient in self-splicing.

Exons↗
PubMed1989

Identification of a T4 gene required for bacteriophage mRNA processing.

A ribonucleolytic activity that cleaves within the Shine/Dalgarno sequences of the bacteriophage T4 motA and ORF2 mRNAs was recently described. We have identified additional sites of processing within several other ribosome binding sites, including two sites in the polycistronic frd transcript. Deletion mutants (farP) that overproduce the product of frd are defective in this mRNA processing. The mutants were used to identify processing events dependent on the T4 activity including attack at nuclease-sensitive sites within the coding sequences of some genes and within the intercistronic region 5' of gene 43. All known processing sites lie within similar sequences. Another mutant in mRNA processing carries a point mutation in one of the open reading frames (orf61.9) removed by the farP deletions. Introduction of a cloned copy of this open reading frame into a unique site in the chromosome of farP phage is sufficient to restore mRNA processing capability. The open reading frame probably encodes the T4 regB protein.

Base Sequence↗