Experimental vaccines against measles in a world of changing epidemiology

Vaccination with the current live attenuated measles vaccine is one of the most successful and cost-effective medical interventions. However, as a result of persisting maternal antibodies and immaturity of the infant immune system, this vaccine is poorly immunogenic in children <9 months old. Immunity against the live vaccine is less robust than natural immunity and protection less durable. There may also be some concern about (vaccine) virus spread during the final stage of an eventual measles eradication program. Opinions may differ with respect to the potential threat that some of these concerns may be to the World Health Organisation goal of measles elimination, but there is a consensus that the development of new measles vaccines cannot wait. Candidate vaccines are based on viral or bacterial vectors expressing recombinant viral proteins, naked DNA, immune stimulating complexes or synthetic peptides mimicking neutralising epitopes. While some of these candidate vaccines have proven their efficacy in monkey studies, aerosol formulated live attenuated measles vaccine are evaluated in clinical trials.     

The diverse world of coenzyme A binding proteins

Coenzyme A is involved in a number of important metabolic pathways. Recently the structures of several coenzyme A binding proteins have been determined. We compare in some detail the structures of seven different coenzyme A protein complexes. These seven proteins all have distinctly different folds.     

Developmental expression of transforming growth factors alpha and beta in mouse fetus.

Expression of mRNA for transforming growth factor alpha (TGF-alpha) and TGF-beta 1 during the fetal development of mice was evaluated by in situ hybridization. TGF-alpha mRNA was detected in 9- and 10-day fetuses but was absent in older fetuses. TGF-alpha mRNA-containing cells were found in the placenta, otic vesicle, oral cavity, pharyngeal pouch, first and second branchial arches, and developing kidneys. mRNA for TGF-beta 1 was present in hematopoietic cells of blood islands and capillaries and in the liver as it began to bud off on day 10 and function as a hematopoietic organ.     

Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin.

Melanoma growth stimulatory activity (MGSA) is a mitogenic polypeptide secreted by Hs294T human melanoma cells. Comparison of the N-terminal sequences of the 13 and 16 kd MGSA species with the cDNA sequence revealed that the mature form of human MGSA is maximally 73 amino acids long. Expression of the cDNA in mammalian cells results in the secretion of this peptide with mitogenic activity. MGSA is structurally related to the platelet-derived beta-thromboglobulin and to several other polypeptides. These factors may constitute a family of growth factors. MGSA mRNA was detected in a variety of cell types. The level of MGSA mRNA in melanoma cells is strongly elevated by treatment with MGSA. MGSA is the gene product of a recently detected gene gro. The gene was mapped to chromosome 4 (region q13----q21). This same region also contains genes for two of the structurally related factors, for c-kit, a receptor for an as yet unidentified ligand, and for 'piebald trait', an inherited skin pigmentation disorder.     

Isolation and characterization of a fruit-specific cDNA and the corresponding genomic clone from tomato

Differential screening of a cDNA bank constructed from ripe tomato fruit mRNA allowed the isolation of cDNA clone 2A11 which is entirely fruit-specific, is expressed at steadily increasing levels from anthesis to breaker, and accounts for approximately 1% of the messenger RNA in mature tomato fruit. A genomic clone corresponding to the 2A11 cDNA was isolated from a tomato genomic library. Sequence comparison of the cDNA clone with the genomic clone shows they are identical over the shared region with the genomic clone possessing a single large intron near the 5 end of the message.The open reading frame of 2A11 would encode a sulfur-rich polypeptide 96 amino acids in length. The identity of the putative protein is unknown. In situ hybridization shows that the 2A11 message is found throughout the pericarp cells in a tomato fruit. In contrast, in situ hybridization of early ripening stages with a polygalacturonase probe shows higher mRNA levels in cells of the outer pericarp and cells surrounding the vascular regions of the pericarp.