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D Arnot

Publications and source records attributed to D Arnot.

10 recordsLinked to original sources
PubMed2001

A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver.

Carbohydrates mediate their conversion to triglycerides in the liver by promoting both rapid posttranslational activation of rate-limiting glycolytic and lipogenic enzymes and transcriptional induction of the genes encoding many of these same enzymes. The mechanism by which elevated carbohydrate levels affect transcription of these genes remains unknown. Here we report the purification and identification of a transcription factor that recognizes the carbohydrate response element (ChRE) within the promoter of the L-type pyruvate kinase (LPK) gene. The DNA-binding activity of this ChRE-binding protein (ChREBP) in rat livers is specifically induced by a high carbohydrate diet. ChREBP's DNA-binding specificity in vitro precisely correlates with promoter activity in vivo. Furthermore, forced ChREBP overexpression in primary hepatocytes activates transcription from the L-type Pyruvate kinase promoter in response to high glucose levels. The DNA-binding activity of ChREBP can be modulated in vitro by means of changes in its phosphorylation state, suggesting a possible mode of glucose-responsive regulation. ChREBP is likely critical for the optimal long-term storage of excess carbohydrates as fats, and may contribute to the imbalance between nutrient utilization and storage characteristic of obesity.

Animals↗
PubMed1995

Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum.

A gene encoding a novel cdc2-related protein kinase has been identified in Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to regions that are conserved in members of the cdc2 gene family. This gene, called Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA gene family, members of which are negative regulators of cell growth in vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific accumulation of mRNA in gametocytes.

Amino Acid Sequence↗
PubMed1984

Structure and polymorphism of the HLA class II SB light chain genes.

The HLA Class II region contains at least three groups of loci, DR, DC and SB, which play an important role in the immune response. The antigens encoded at these loci are heterodimers composed of an alpha and a beta chain. The sequence of a complete Class II beta cDNA clone whose sequence agrees closely with the limited N-terminal protein sequence available for the SB beta chain is reported. In addition the structure and coding sequence of genomic SB beta clones of two different SB haplotypes has been obtained and allows definition of some polymorphic regions. The SB beta gene appears to undergo alternate splicing at its 3' end, resulting in expression of two different intracytoplasmic regions. Partial sequencing of a second non-allelic SB beta-like gene, SX beta, indicates that it is a pseudogene.

Amino Acid Sequence↗
PubMed1984

Inter-locus and intra-allelic polymorphisms of HLA class I antigen gene mRNA.

We have constructed cDNA clone libraries from two lymphoblastoid cell lines, JY (HLA-A2, B7, C untypeable) and LB (HLA-A28, B40, Cw3), and isolated clones encoding class I HLA antigens. We have characterized short oligonucleotide probes derived from the coding region of the HLA class I antigens which are specific for the HLA-A and -B loci. These probes have been used to subdivide the class I cDNA clones into subclasses. DNA sequencing of several HLA-A and -B related clones has allowed us to extend the primary structural characterization of these cell-surface antigens. This analysis has also detected a sequence polymorphism at the HLA-A locus, indicating that the previously considered homozygous typing cell line LB expresses two alleles of similar, although not identical, serological specificity.

Alleles↗
PubMed1984

Circumsporozoite gene of plasmodium cynomolgi (Gombak):cDNA cloning and expression of the repetitive circumsporozoite epitope.

We report the identification, sequence, and expression in Escherichia coli of the immunodominant epitope of the circumsporozoite (CS) gene of Plasmodium cynomolgi (Gombak), a simian malaria parasite. This epitope is encoded by a DNA sequence that is tandemly repeated 10 times in the cDNA clone. Subclones that contain and express only repeats and in variable number have been constructed. We show that the binding of a specific anti-CS protein monoclonal antibody correlates positively with the number of repeats in each subclone. The CS gene of another strain of P. cynomolgi (NIH) encodes an immunodominant epitope that is immunologically distinct from that of the Gombak strain. We present evidence that these two CS genes share extensive overall homology, although the nucleotide sequences that encode the epitopes appear to be unrelated.

Animals↗
PubMedDate not supplied

Unstable malaria in Sudan: the influence of the dry season. Clone multiplicity of Plasmodium falciparum infections in individuals exposed to variable levels of disease transmission.

Studies of infection and immunity to malaria often take little account of the fact that the amount of infectious challenge individuals receive is very variable. Classic studies in areas of holoendemic transmission showed that clinical immunity develops quite rapidly during childhood, although the processes through which increasing levels of resistance to infection are acquired are still not understood. However, holoendemic transmission is one end of the spectrum of malaria epidemiology and the development of clinical immunity is also affected by factors such as the infection rate and the local parasite species composition. An exceptionally simple type of malaria transmission occurs during the short, autumnal malaria outbreaks of the Sudanese sahel-savannah belt, where a sparse 200-500 mm of rain falls in 2-3 summer months, Plasmodium falciparum causes > 95% of malaria cases in most areas, and the entomological inoculation rate (EIR) is very low by African standards; thus the population dynamics of malaria parasites are less affected by super-infection. A comparison of certain features of parasite genetic diversity, particularly the average number of parasite clones present in infections in the Sudanese sahel and in malaria study sites with different levels of transmission, is presented. It is proposed that increasing EIRs are associated with progressively smaller increases in the average number of malaria parasite clones per host and the implications of this relationship for studies on malaria infection and immunity are discussed.

Animals↗
PubMedDate not supplied

Isotypic and allotypic variation of human class II histocompatibility antigen alpha-chain genes.

DNA sequences of four human class II histocompatibility antigen alpha chain DNA sequences (derived from cDNA and genomic clones representing DC1 alpha, DC4 alpha, DX alpha and SB alpha) are presented and compared to DR alpha and to mouse I-A alpha and I-E alpha sequences. These data suggest possible mechanisms for the generation of polymorphism and the evolution of the DR, DC and SB families.

Alleles↗