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Author

George A. M. Cross

Other affiliations: Wellcome Trust, Medical Research Council, Exelixis  ...read more
Bio: George A. M. Cross is an academic researcher from Rockefeller University. The author has contributed to research in topics: Trypanosoma brucei & Gene. The author has an hindex of 76, co-authored 211 publications receiving 18206 citations. Previous affiliations of George A. M. Cross include Wellcome Trust & Medical Research Council.


Papers
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Journal ArticleDOI
TL;DR: A dual-promoter approach is developed, for expressing highly toxic products and generating conditional gene knock-outs, using back-to-back constitutive T7 and tetracycline-responsive PARP promoters to drive expression of the selectable marker and test gene, respectively.

1,351 citations

Journal ArticleDOI
TL;DR: Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.
Abstract: Soluble glycoproteins have been purified from a series of clones of Trypanosoma brucei 427. Each clone yielded a characteristic predominant glycoprotein which induced clone-specific immunity to trypanosome infection in mice. These glycoproteins were shown by specific labelling and enzyme digestion of cells to be the major components of the trypanosome surface coat. Each glycoprotein consisted of a single polypeptide chain having an apparent molecular weight of 65 000 (as measured by SDS-polyacrylamide gel electrophoresis) and containing around 600 amino acid and 20 monosaccharide residues. Preliminary structural studies indicated large changes in amino acid sequence dispersed over a considerable length of the polypeptide chain. Proteolytic activity was demonstrated in semi-purified trypanosome extracts, providing one reason for the heterogeneity sometimes observed in surface glycoprotein antigen preparations.

845 citations

Journal ArticleDOI
TL;DR: The isolation and the sequence of the gene for the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) from two pyrimethamine-resistant clones of Plasmodium falciparum, HB3 and 7G8 is described and it is highly likely that this difference is involved in the mechanism of drug resistance in HB3.
Abstract: We describe the isolation and the sequence of the gene for the bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS; EC 1.5.1.3 and EC 2.1.1.45, respectively) from two pyrimethamine-resistant clones of Plasmodium falciparum, HB3 and 7G8. We have also derived the sequence of the DHFR portion of the gene, by amplification using polymerase chain reaction, for the pyrimethamine-sensitive clone 3D7 and the pyrimethamine-resistant strains V-1, K-1, Csl-2, and Palo-alto. The deduced protein sequence of the resistant DHFR portion of the enzyme from HB3 contained a single amino acid difference from the pyrimethamine-sensitive clone 3D7. It is highly likely that this difference is involved in the mechanism of drug resistance in HB3. The sequence of the DHFR gene from other pyrimethamine-resistant strains contains the same amino acid difference from the sensitive clone 3D7. However, they all differ at one other site that may influence pyrimethamine resistance. The DHFR-TS gene is present as a single copy on chromosome 4 in all pyrimethamine-sensitive and pyrimethamine-resistant isolates tested. Therefore, the molecular basis of pyrimethamine resistance in the parasites tested is not amplification of the DHFR-TS gene.

499 citations

Journal ArticleDOI
TL;DR: Serological Cross-Reactions and Indications of a Glycolipid Anchor and the Hydrophobic Constituents are studied.
Abstract: CHARACTERIZATION OF GLYCOLIPID ANCHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Indications of a Glycolipid Anchor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . 5 Chemical Analysis . 5 The Ethanolamine-Glycan-Inositol Core . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Variations on the Core Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 The Hydrophobic Constituents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Serological Cross-Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1

493 citations

Journal ArticleDOI
TL;DR: The COOH terminus of the externally disposed variant surface glycoprotein (VSG) of the eukaryotic pathogenic protozoan Trypanosoma brucei strain 427 variant MITat 1.4 (117) is covalently linked to a novel phosphatidylinositol-containing glycolipid.

389 citations


Cited by
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Journal ArticleDOI
TL;DR: It is clear now that degradation of cellular proteins is a highly complex, temporally controlled, and tightly regulated process that plays major roles in a variety of basic pathways during cell life and death as well as in health and disease.
Abstract: Between the 1960s and 1980s, most life scientists focused their attention on studies of nucleic acids and the translation of the coded information. Protein degradation was a neglected area, conside...

3,990 citations

Journal Article
TL;DR: This volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of the instrument and its ancillary tools are simply and well presented.
Abstract: I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

3,197 citations

Journal ArticleDOI
07 Feb 1992-Cell
TL;DR: It is shown that a protein with a glycosylphosphatidyl inositol (GPI) anchor can be recovered from lysates of epithelial cells in a low density, detergent-insoluble form, supporting the model proposed by Simons and colleagues for sorting of certain membrane proteins to the apical surface after intracellular association with glycosphingolipids.

2,970 citations

Journal ArticleDOI
TL;DR: An analysis of aligned sequences of the four nuclear and two mitochondrial rRNA genes identified regions of these genes that are likely to be useful to address phylogenetic problems over a wide range of levels of divergence.
Abstract: Ribosomal DNA (rDNA) sequences have been aligned and compared in a number of living organisms, and this approach has provided a wealth of information about phylogenetic relationships. Studies of rDNA sequences have been used to infer phylogenetic history across a very broad spectrum, from studies among the basal lineages of life to relationships among closely related species and populations. The reasons for the systematic versatility of rDNA include the numerous rates of evolution among different regions of rDNA (both among and within genes), the presence of many copies of most rDNA sequences per genome, and the pattern of concerted evolution that occurs among repeated copies. These features facilitate the analysis of rDNA by direct RNA sequencing, DNA sequencing (either by cloning or amplification), and restriction enzyme methodologies. Constraints imposed by secondary structure of rRNA and concerted evolution need to be considered in phylogenetic analyses, but these constraints do not appear to impede seriously the usefulness of rDNA. An analysis of aligned sequences of the four nuclear and two mitochondrial rRNA genes identified regions of these genes that are likely to be useful to address phylogenetic problems over a wide range of levels of divergence. In general, the small subunit nuclear sequences appear to be best for elucidating Precambrian divergences, the large subunit nuclear sequences for Paleozoic and Mesozoic divergences, and the organellar sequences of both subunits for Cenozoic divergences. Primer sequences were designed for use in amplifying the entire nuclear rDNA array in 15 sections by use of the polymerase chain reaction; these "universal" primers complement previously described primers for the mitochondrial rRNA genes. Pairs of primers can be selected in conjunction with the analysis of divergence of the rRNA genes to address systematic problems throughout the hierarchy of life.

2,439 citations

01 Jan 2011
TL;DR: The sheer volume and scope of data posed by this flood of data pose a significant challenge to the development of efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data.
Abstract: Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

2,187 citations