Biomedical subjects

P Jeffs

Publications and source records attributed to P Jeffs.

6 recordsLinked to original sources

PubMed1998

Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages.

In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.

Animals↗

PubMed1992

Probing structural factors stabilizing antisense oligonucleotide duplexes: NMR studies of a DNA.DNA duplex containing a formacetal linkage.

The duplex formed by annealing the formacetal backbone modified dodecamer d-(CGCGTTOCH2OTTGCGC) to its complementary strand, d(GCGCAAAACGCG) (duplex I), has been studied by NMR techniques and analyzed with reference to its unmodified counterpart (duplex II). Comparison of parameters such as 2D cross-peak intensities, coupling constants, and spectral patterns indicates that structural perturbations caused by the incorporation of the formacetal linkage are minimal and localized to the central T4.A4 block. Duplex I adopts a B-type helical conformation with regular Watson-Crick base pairing and normal minor groove width. The methylene group is accommodated along the phosphate backbone in a conformation similar to that of the PO2 group found in the B-form DNA family. The central T6-T7 base pairs of duplex I melt simultaneously with the duplex, indicating a cooperative transition to single strands. Although the formacetal linkage affects global melting, as evidenced by a 3 degree C reduction in Tm for duplex I with respect to duplex II, the present study indicates that this is not the result of localized premelting at the formacetal site of duplex I but rather reflects the subtle interplay of several structural and energy factors which need to be further explored.

Base Sequence↗

PubMed1992

Cell death in cranial neural crest development.

The rhombencephalic neural crest, crucial to the patterning and development of many craniofacial structures, migrates laterally from the dorsal hindbrain, but not as a continuous sheet. We have used a vital dye to demonstrate a discontinuous pattern of cell death in the dorsal midline of the avian rhombencephalon associated with the migration of the neural crest. Whilst cell death commences in the dorsal midline of the presumptive mesencephalon at stage 8, two distinct domains of cell death are apparent in the rhombencephalon by stage 11. The rostral domain lies over primary rhombomere RhA1 and rhombomere rh3, while the caudal domain occurs on the neural midline between the otic vesicles, in the region of rh5. Using a marker for the neural crest, we show that the rostral and caudal domains of cell death correlate with the absence of neural crest migration from rh3 and rh5. Thus segment-specific cell death in the dorsal region of particular rhombomeres may account for their subsequent failure to contribute to the cranial neural crest.

Animals↗

PubMed1992

A segmented pattern of cell death during development of the chick embryo.

During the early development of the chick embryo, specific groups of cells die in characteristic patterns. In this study, Nile Blue sulphate staining was used to reveal a novel pattern of segmentally repeated cell death in the paraxial mesoderm of the chick prior to stage 23. This pattern varies according to the developmental stage of the embryo and shifts rostrocaudally, corresponding to progressing somite differentiation. Initially, during early somite differentiation, cell death is restricted to the rostral half of the somite (the rostral pattern of cell death). After the somite has differentiated into dermomyotome and sclerotome, dead cells appear in superficial tissues in a pyramidal pattern which lies in register (rostrocaudally) with the central part of the sclerotome. Finally, small bands of dying cells are seen between the neural tube and the expanding sclerotome. This third pattern (the ventral path) lies in register with the rostral part of the caudal half of the sclerotome. We show by fluorescent labelling of the migrating neural crest that these patterns of cell death correspond to the routes of neural crest migration. In addition, serial sectioning of stage 23 chick embryos confirms that the position of dying cells correlates with the known routes of neural crest migration and with the sites of development of certain neural crest-derived tissues.

Animals↗

PubMed1991

Processed pseudogenes in Drosophila.

Two species of Drosophila, D. yakuba and D. teissieri, possess pseudogenes of Adh. These pseudogenes lack introns and map to chromosome arm 3R, rather than to chromosome arm 2L, wherein are located the functional Adh genes. Their structure suggests that the pseudogenes arose from reverse transcripts. Because the pseudogenes map to homologous sites in both species, they presumably arose before these species diverged. Remarkably, the pattern of base substitution in the pseudogenes differs between sites that correspond to degenerate and non-degenerate codon positions in their functional paralogs.

Alcohol Dehydrogenase↗

PubMed1970

Isolation of -L-glutaminyl 4-hydroxybenzene and -L-glutaminyl 3,4-benzoquinone: a natural sulfhydryl reagent, from sporulating gill tissue of the mushroom Agaricus bisporus.

Early in the development of spores, there appears in gill tissue of the mushroom Agaricus bisporus a red pigment that inhibits mitochondrial respiration. The inhibitor and its immediate precursor were isolated from the mushroom and identified as gamma-L-glutaminyl 3,4-benzoquinone (I) and gamma-L-glutaminyl 4-hydroxybenzene (II), respectively, neither of which had previously been described. II was synthesized chemically and the synthetic material was identical with isolated II in all regards. An enzyme that oxidizes II to I was isolated concurrently. I reacts unusually rapidly, completely, and at low concentration with the sulfhydryl groups of various mitochondrial enzymes, accounting for its originally observed properties. It may also prove of value as a general inhibitor of sulfhydryl-dependent enzymes.

Basidiomycota↗