Biomedical subjects

S J Sowerby

Publications and source records attributed to S J Sowerby.

10 recordsLinked to original sources

PubMed2001

Differential adsorption of nucleic acid bases: Relevance to the origin of life.

The adsorption of organic molecules onto the surfaces of inorganic solids has long been considered a process relevant to the origin of life. We have determined the equilibrium adsorption isotherms for the nucleic acid purine and pyrimidine bases dissolved in water on the surface of crystalline graphite. The markedly different adsorption behavior of the bases describes an elutropic series: guanine > adenine > hypoxanthine > thymine > cytosine > uracil. We propose that such differential properties were relevant to the prebiotic chemistry of the bases and may have influenced the composition of the primordial genetic architecture.

Adenine↗

PubMed2001

Origins of life: a route to nanotechnology.

The origins of life and nanotechnology are two seemingly disparate areas of scientific investigation. However, the fundamental questions of life's beginnings and the applied construction of a Drexlerian nanotechnology both share a similar problem; how did and how can self-reproducing molecular machines originate? Here we draw attention to the coincidence between nanotechnology and origins research with particular attention paid to the spontaneous adsorption and scanning tunneling microscopy investigation of purine and pyrimidine bases self-organized into monolayers, adsorbed to the surfaces of crystalline solids. These molecules which encode biological information in nucleic acids, can form supramolecular architectures exhibiting enantiomorphism with the complexity to store and encode putative protobiological information. We conclude that the application of nanotechnology to the investigation of life's origins, and vice versa, could provide a viable route to an evolution-driven synthetic life.

Life↗

PubMed2000

Self-programmable, self-assembling two-dimensional genetic matter.

Putative two-dimensional coding systems can be constructed from aqueous solutions of purine and pyrimidine nucleic acid bases evaporated at moderate temperatures on the surfaces of inorganic solids. The resultant structures are monolayers which are formed spontaneously by molecular self-assembly and they have been observed with molecular resolution by scanning tunnelling microscopy (STM). When formed from solutions of a single base, the monolayers of adenine and uracil have crystalline characteristics and the STM images can be interpreted in terms of the geometrical placement of planar arranged molecules that interact laterally by intermolecular hydrogen bonding. When formed from solutions containing a mixture of adenine and uracil, the monolayers have aperiodic structures. Small crystalline domains within these monolayers can be interpreted in terms of the single phase configurations of the molecules and the remaining aperiodic structures can presumably be interpreted, geometrically, in terms of the 21 theoretically possible adenine-adenine, uracil-uracil and adenine-uracil hydrogen bonding interactions. We propose that combinatorial arrangements of planar arranged purine and pyrimidine bases could provide the necessary complexity to act as a primitive genetic mechanism and may have relevance to the origin of life.

Adenine↗

PubMed1999

Methylation sequencing analysis refines the region of H19 epimutation in Wilms tumor.

Differential DNA methylation of the parental alleles has been implicated in the establishment and maintenance of the monoallelic expression of imprinted genes. H19 and IGF2 are oppositely imprinted with only the maternal and the paternal alleles expressed, respectively. In Wilms tumor, a childhood renal neoplasm, loss of the H19/IGF2 imprinted expression pattern results in silencing of H19 and biallelic expression of IGF2. This was shown to be associated with biallelic methylation of the H19 promoter in the tumor and the adjacent kidney tissue suggesting that epigenetic H19 silencing is an early event in Wilms tumorigenesis. An imprinting mark region characterized by paternal allele-specific methylation has been suggested to reside in a GC-rich region of 400-base pair direct repeats starting at -2 kilobase pairs (kb) relative to the H19 transcription start and extending upstream. The upstream boundary of the potential paternal methylation imprint of the H19 gene has yet to be defined. We sought to define this upstream imprint boundary and investigate whether Wilms tumors with loss of imprinting are biallelically methylated in this imprinting mark region. The analysis of 6.6 kb of new upstream H19 sequence determined in this study identified a series of the direct 400-base pair repeats that extends to approximately -5.3 kb relative to the transcription start. DNA methylation analyses indicated that the upstream boundary of the potential imprint may coincide with the 5' end of the direct repeats. We found that Wilms tumors with loss of imprinting are biallelically methylated in the H19 upstream repeat region, and we suggest that pathological methylation in this region is the epigenetic error that initiates H19 silencing.

Blotting, Southern↗

PubMed1999

Scanning tunnelling microscopy and molecular modelling of xanthine monolayers self-assembled at the solid-liquid interface: relevance to the origin of life.

The development of scanning tunnelling microscopy (STM) has allowed examination of inorganic crystalline surfaces and their interactions with organic adsorbates with unparalleled resolution. As a novel technique in origin of life studies, the application of STM is detailed with particular attention paid to the methods employed in the analysis of organic monolayer structures. STM imaging and molecular modelling of self-assembled monolayers of the purine base, xanthine, formed on the surfaces of graphite and molybdenum disulfide are presented as an example. The putative role of such structures in the origin of life is discussed.

Hydrogen Bonding↗

PubMed1999

3' BCR recombines with IGL locus in BCR-ABL-positive philadelphia-negative chronic myeloid leukemia.

We have isolated the 3' BCR breakpoint junction of a complex BCR-ABL1 rearrangement found in leukemic cells with a cytogenetically normal karyotype, and the corresponding germline fragment that spanned the 3' BCR recombination site. Fluorescence in situ hybridization localized the 3' BCR recombination site to 22q11, about 350-600 kb proximal to BCR. Restriction map and DNA sequence comparisons indicated that 3' M-Bcr had recombined at a site within the variable region (Itv Region IV) of the immunoglobulin lambda (IGL) locus. Somatic rearrangement of DNA sequences (variable, joining, and constant regions) within the IGL locus, as in other Ig and TCR loci, represents the basis for human antibody diversity. Misrecombination of these somatically rearranging sites has been associated with chromosomal rearrangements in lymphoid leukemia and lymphoma, but there are no previous descriptions of IGL involvement in genomic aberrations associated with myeloid leukemia. Genes Chromosomes Cancer 26:366-371, 1999.

3' Untranslated Regions↗

PubMed1998

The role of self-assembled monolayers of the purine and pyrimidine bases in the emergence of life.

The experimental evidence for the spontaneous formation and structure determination of two-dimensional monolayers of the purine and pyrimidine bases is examined. The plausibility of such structures forming spontaneously at the solid-liquid interface following their prebiotic synthesis suggests a functional role for them in the emergence of life. It is proposed that prebiotic interactions of enantiomorphic monolayers of mixed base composition with racemic amino acids might be implicated in a simultaneous origin of a primitive genetic coding mechanism and biomolecular homochirality. The interactions of these monolayers with carbohydrates and other derivatives is also discussed.

Adsorption↗

PubMed1998

The BCR gene recombines preferentially with Alu elements in complex BCR-ABL translocations of chronic myeloid leukaemia.

Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.

Base Sequence↗

PubMed1996

Chiral symmetry breaking during the self-assembly of monolayers from achiral purine molecules.

Scanning tunneling microscopy was used to investigate the structure of the two-dimensional adsorbate formed by molecular self-assembly of the purine base, adenine, on the surfaces of the naturally occurring mineral molybdenite and the synthetic crystal highly oriented pyrolytic graphite. Although formed from adenine, which is achiral, the observed adsorbate surface structures were enantiomorphic on molybdenite. This phenomenon suggests a mechanism for the introduction of a localized chiral symmetry break by the spontaneous crystallization of these prebiotically available molecules on inorganic surfaces and may have some role in the origin of biomolecular optical asymmetry. The possibility that purine-pyrimidine arrays assembled on naturally occurring mineral surfaces might act as possible templates for biomolecular assembly is discussed.

Adenine↗

PubMed1993

DNA sequence analysis of the major breakpoint cluster region of the BCR gene rearranged in Philadelphia-positive human leukemias.

We sought sequence characteristics that might explain the apparent high recombination frequency of the 5-kb BglII segment containing M-bcr exons 1, 2 and 3, and the intron to exon 4. An Alu sequence (subfamily Sx), in 5'-->3' orientation, lay in the middle of a 3-kb region that contains the great majority of Philadelphia chromosome breakpoint sites. The breakpoint of only one out of five chronic myeloid leukemia patients, for whom the BCR breakpoint site had been sequenced, was located within this Alu. Other features of interest for recombination were a 51-bp AT-rich region close to the 3' end, six hypervariable minisatellite consensus octamers, GC[A/T]GG[A/T]GG, six lymphoid recombinase heptamer signal sequences, one nonamer and a 16-bp inverted repeat. Dot matrix comparisons of the 5-kb M-bcr sequence with a 3-kb m-bcr2 segment showed significant homology only in corresponding Alu sequences.

Base Sequence↗