PubMed HealthSearch

Biomedical subjects

A Gibbs

Publications and source records attributed to A Gibbs.

16 recordsLinked to original sources

Is There Potential Clinical Utility in Reporting Variants of Uncertain Significance From Prenatal Sequencing?

OBJECTIVE: Prenatal sequencing of fetuses with abnormalities detected on imaging is expanding globally. Debate continues over whether variants of uncertain significance (VUS) should be reported prenatally, with some recent national position statements opposing this. In England, VUS that fit the fetal phenotype and require little further evidence for upgrade are discussed at multidisciplinary team (MDT) meetings to determine whether to report. We review the VUS reported by one English laboratory that provides prenatal sequencing to half of England. METHOD: The laboratory's database was searched from 01/10/2020 to 30/04/2025 to ascertain all cases where a VUS was reported. Pregnancy outcomes were obtained from local clinical teams to determine whether the VUS status had been resolved. RESULTS: VUS were reported in 41/881 fetuses sequenced. Follow-up data were available for 38/41 cases, of which 23 were subsequently upgraded to likely pathogenic and 1 downgraded to likely benign. The most common reason for upgrade was new information from post-mortem or postnatal review (17/23). CONCLUSION: There is clinical utility in reporting VUS from prenatal sequencing following MDT discussion. Although reporting VUS leaves parents with uncertainty, follow up (including post-mortem when applicable) resolves this in over 50% of cases (79% of cases re-examined pre- or postnatally).

Humans

Origins of genes: "big bang" or continuous creation?

Many protein families are common to all cellular organisms, indicating that many genes have ancient origins. Genetic variation is mostly attributed to processes such as mutation, duplication, and rearrangement of ancient modules. Thus it is widely assumed that much of present-day genetic diversity can be traced by common ancestry to a molecular "big bang." A rarely considered alternative is that proteins may arise continuously de novo. One mechanism of generating different coding sequences is by "overprinting," in which an existing nucleotide sequence is translated de novo in a different reading frame or from noncoding open reading frames. The clearest evidence for overprinting is provided when the original gene function is retained, as in overlapping genes. Analysis of their phylogenies indicates which are the original genes and which are their informationally novel partners. We report here the phylogenetic relationships of overlapping coding sequences from steroid-related receptor genes and from tymovirus, luteovirus, and lentivirus genomes. For each pair of overlapping coding sequences, one is confined to a single lineage, whereas the other is more widespread. This suggests that the phylogenetically restricted coding sequence arose only in the progenitor of that lineage by translating an out-of-frame sequence to yield the new polypeptide. The production of novel exons by alternative splicing in thyroid receptor and lentivirus genes suggests that introns can be a valuable evolutionary source for overprinting. New genes and their products may drive major evolutionary changes.

Biological Evolution

Familial mesothelioma. Details of 17 cases with histopathologic findings and mineral analysis.

Nine new cases of mesothelioma clustering in four families are described, and additional information is provided on four previously reported families. All of the members of these families had some exposure to asbestos. Diagnoses were confirmed histologically, and the relevance of the histologic pattern is discussed after the literature review. The lung mineral fiber burden was quantified in patients by transmission electron microscopic examination and energy-dispersive x-ray analysis, and this confirmed significant exposure to amphibole asbestos in all patients. Evidence supporting an increased incidence of mesothelioma in family members is discussed.

Aged

Comparisons of the genomic sequences of erysimum latent virus and other tymoviruses: a search for the molecular basis of their host specificities.

The nucleotide sequence of the genome of erysimum latent tymovirus (ELV) has been determined. It closely resembles those of the other four sequenced tymoviral genomes in its gene organization and composition, but is the smallest (6034 nucleotides) and most distinct of them. Furthermore the 78 non-coding nucleotides at the 3' terminus of the ELV genome are unable to form a complete tRNA-like structure like that reported for other tymoviruses. Comparisons of the five tymovirus genomes and their encoded proteins indicate that they have probably evolved from the progenitor tymovirus by independent progressive mutational change without genetic recombination. Comparisons of the sequences of the two non-virion proteins of five tymoviruses, and virion proteins of 17 tymoviruses, revealed no specific similarities between those of ELV and turnip yellow mosaic virus that could explain why their host ranges and symptoms are so similar, yet differ, in this respect, from ononis yellow mosaic, kennedya yellow mosaic and eggplant mosaic tymoviruses.

Amino Acid Sequence

Lethal synergistic action of toxins of bacteria isolated from sudden infant death syndrome.

AIM: To test the hypothesis that lethal toxins of bacteria associated with sudden infant death syndrome (SIDS) can act synergistically. METHODS: Bacteria occurring together in the nasopharynx of cases of cot death were studied. The lethal toxicity of crude toxin preparations was determined over a range of dilutions by injections into the chorioallantoic vein of the chick embryo. Toxin preparations of low lethality for the chick embryo SIDS model were then tested in combination. RESULTS: Staphylococcus aureus toxin preparations showed low lethality when tested alone, even at low dilution. At 1 in 100 dilution S aureus toxin was lethal to one out of 15 chick embryos. Escherichia coli toxin preparations showed high lethality except on high dilution (1 in 80) when lethality fell to two out of 15 of chick embryos. When the same toxin preparations were tested simultaneously in combination, lethality rose to 14 out of 15. Similar findings were observed over a range of toxin dilutions. This finding was highly significant (p = 0.0012). CONCLUSIONS: That synergy between toxins can enhance the lethality of toxins elaborated by bacteria associated with SIDS.

Animals

Epidemiological analysis of a methicillin-resistant Staphylococcus aureus outbreak using restriction fragment length polymorphisms of genomic DNA.

The genomic DNA of 58 isolates of methicillin-resistant Staphylococcus aureus (MRSA) obtained during an infection outbreak at two major Canberra hospitals was analysed for restriction fragment length polymorphism (RFLP) by digestion with the endonuclease SmaI and resolution of the fragments by pulsed-field gel electrophoresis. Based on the fraction of common fragments generated by the endonuclease, DNA similarities among the isolates were estimated. Distance matrix analysis showed that the MRSA isolates could be divided into two major clusters (RFLP types I and II) and one minor one (type 46). A fourth group of miscellaneous isolates was found to be heterogeneous in terms of DNA sequence similarity. The epidemiological data indicated that RFLP type I was most common in the intensive care units in the two hospitals, with particular subtypes of RFLP type I concentrated in individual units. RFLP type II and the miscellaneous group were more generally distributed. Type 46 isolates appear to be related to a group which was present in epidemics in Melbourne hospitals in the early 1980s. Using the standard phage set, the RFLP type I group was largely untypable. However, type II isolates were all phage typable, with a shared susceptibility to phages 29/85/95/90; type 46 isolates had a shared susceptibility to phages 85/90. The miscellaneous isolates were of variable phage types.

Australia

Particles produced during a mixed infection by two tobamoviruses contain coat proteins of both viruses.

Particles from plants mixedly infected with two tobamoviruses, whose particles differ in density, were all of a single, intermediate density, suggesting that they contain both coat proteins and that the proteins occur in the same proportion in all particles. Plants inoculated with the genome-containing particles of one of the tobamoviruses together with the noninfective, short, coat protein messenger-containing particles of the other yielded only particles with the density of the first;.there was no evidence of complementation.

Mosaic Viruses

In vitro translation of polyribosome-associated RNAs from tobamovirus-infected plants.

RNAs associated with polyribosomes in plants infected with the U2 strain of tobacco mosaic virus (TMV) or with sunnhemp mosaic virus have been isolated. Most are about 0.35 X 10(6) daltons in weight. They translate efficiently in vitro to produce their respective coat proteins which were identified by their serological behavior and peptide composition. They also reassemble in vitro with coat protein. The coat protein of sunnhemp mosaic virus reassembles more quickly than that of TMV U2.

Cell-Free System

Translation in vitro of artificially produced fragments of a tobamovirus genome.

Particles of the U2 strain of tobacco mosaic virus (TMV) were partly disassembled by SDS, treated with RNases and then phenol, and yielded RNA molecules one quarter to half the size of the intact virus genome. These molecules, when translated in vitro, produced the coat protein of the virus. Reassembly experiments indicated that the active messenger molecules were those that most rapidly reassembled with coat protein; the rate of reassembly was greatly diminished by treatment with spleen phosphodiesterase. Particles of sunnhemp mosaic virus (the bean strain of TMV) resist disassembly by detergent much more than those of the U2 strain of TMV.

Cell-Free System

On the nature of the difference in the densities of the particles of two tobamoviruses.

Particles of sunnhemp mosaic virus (SHMV) are denser than those of the U2 strain of tobacco mosaic virus (T2MV) when their densities are estimated by equilibrium centrifugation in gradients of either cesium chloride or Metrizamide; in cesium chloride the densities are 1.318 and 1.307 g/ml, and in Metrizamide they are 1.249 and 1.240 g/ml. Experiments with particles reassembled from homologous or heterologous mixtures of the RNAs and coat proteins of the viruses show that the difference in their densities is determined by their coat proteins. The disassembled coat proteins of the two viruses have the same density, but polymerized SHMV protein is less dense than polymerized T2MV protein. Particles reassembled from homologous or heterologous mixtures of the RNAs and coat proteins of the viruses have the density of the nucleoprotein particles used as the source of protein. The density difference of the two virus nucleoproteins therefore reflects the different behavior of the two proteins on assembly with RNA.

Centrifugation, Density Gradient

Mixed infection with two tobamoviruses: the formation of particles containing the coat protein messenger RNAs of either virus.

Plants mixedly infected with the U2 strain of tobacco mosaic virus (T2MV) and sunnhemp mosaic virus (SHMV) and grown at 35 degrees, yield particles of the same modal lengths (300 and 40 nm) as those found in plants singly infected with SHMV, but not in plants infected with T2MV, which yield only the long particles. At least some of the particles produced in mixedly infected plants contain coat proteins of both viruses. When RNAs from these particles are translated in vitro the coat proteins of both viruses are produced, although when a mixture of RNAs from particles of SHMV and T2MV, grown separately, are translated in vitro only SHMV protein is produced. These and other results suggest that the short particles produced in mixedly infected plants contain both coat protein messengers.

Antigens, Viral

A correlation between the genome compositions of bacteriophages and their hosts.

The base composition of the genomes of bacteriophages and other viruses is, in a very general way, related to the base composition of the genomes of their hosts by the statistically significant linear regression: (phage GC%)=9.12 + 0.74 (host GC%). The significance and possible use of this relationship is discussed.

Coliphages

Soybean virus Z: its characteristics and taxonomy.

Soybean virus Z is a hitherto undescribed virus of soybeans found in Australia. It has a limited host range, attains a low concentration in plants and has a thermal inactivation point of 65 degrees. It has flexuous filamentous particles with a modal length of 610 nm and forms amorphous inclusions, but no pinwheels, in infected cells. It has not been transmitted by aphids or by seed. Its genome is RNA with the composition G23, A26, C25, U26, and its coat protein weights about 2.7 X 104. This virus seems to be unrelated to previously described viruses of soybeans, and does not fall into any of the described virus groups with similar particles.

Plant Viruses