A proteomic view of the Plasmodium falciparum life cycle

The completion of the Plasmodium falciparum clone 3D7 genome provides a basis on which to conduct comparative proteomics studies of this human pathogen. Here, we applied a high-throughput proteomics approach to identify new potential drug and vaccine targets and to better understand the biology of this complex protozoan parasite. We characterized four stages of the parasite life cycle (sporozoites, merozoites, trophozoites and gametocytes) by multidimensional protein identification technology. Functional profiling of over 2,400 proteins agreed with the physiology of each stage. Unexpectedly, the antigenically variant proteins of var and rif genes, defined as molecules on the surface of infected erythrocytes, were also largely expressed in sporozoites. The detection of chromosomal clusters encoding co-expressed proteins suggested a potential mechanism for controlling gene expression.     

Late DNA replication in the sex chromosomes ofDidelphis virginiana

Zusammenfassung Autoradiographisch wurde die späte DNS-Synthese derX- undY-Chromosomen vonDidelphis virginiana (Virginia Opossum) in Knochenmarkzellen untersucht. Die weiblichen Tiere zeigen typische späte Reduplikationsmuster in einemX, die männlichen das späte Reduplikationsmuster inX undY und inY allein.

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This study was supported in part by research grant No. AM-02504 and training grant No. Tl-AM-5277, National Institutes of Health. Dr.Reiss was a predoctoral trainee, National Institute of Arthritis and Metabolic Diseases, U.S. Public Health Service.     

Automatic monitoring of forecast errors

This paper evaluates a variety of automatic monitoring schemes to detect biased forecast errors. Backward cumulative sum (cusum) tracking signals have been recommended in previous research to monitor exponential smoothing models. This research shows that identical performance can be had with much simpler tracking signals. The smoothed-error signal is recommended for α = 0.1, although its performance deteriorates badly as α is increased. For higher α values, the simple cusum signal is recommended. A tracking signal based on the autocorrelation in errors is recommended for forecasting models other than exponential smoothing, with one exception. If the time series has a constant variance, the backward cusum should give better results.     

Isolation of a feline leukaemia provirus containing the oncogene myc from a feline lymphosarcoma

The molecular mechanism by which feline leukaemia virus (FeLV) induces lymphoid malignancy in domestic cats is largely unknown. Using the insertional activation model of c-myc by avian leukosis virus in the induction of bursal lymphoma in chickens, we have now characterized the c-myc locus in feline tissues and investigated the possibility that FeLV may also insert within feline c-myc. We used the 1.5 kilobase (kb) PstI fragment of MC29 v-myc in Southern blot analysis to characterize the structure of the c-myc locus in the DNA of 31 naturally occurring feline lymphomas. Analysis of a cloned c-myc gene from one lymphoma demonstrated that sequences homologous to v-myc occupy 2.6 kb of feline DNA in which a putative intron of 0.5 kb separates sequences homologous to the 5' and 3' exons represented in avian v-myc. We also observed in the DNA of this lymphoma tumour-specific fragments homologous to v-myc. Characterization of these molecularly cloned myc-hybridizing fragments revealed the presence of at least two identical FeLV proviruses 5.5 kb in length, each containing long terminal repeats enclosing a spliced version of the feline myc gene.     

Hedgehog signalling in prostate regeneration, neoplasia and metastasis

Metastatic cancers adopt certain properties of normal cells in developing or regenerating organs, such as the ability to proliferate and alter tissue organization. We find here that activity of the Hedgehog (Hh) signalling pathway, which has essential roles in developmental patterning, is required for regeneration of prostate epithelium, and that continuous pathway activation transforms prostate progenitor cells and renders them tumorigenic. Elevated pathway activity furthermore distinguishes metastatic from localized prostate cancer, and pathway manipulation can modulate invasiveness and metastasis. Pathway activity is triggered in response to endogenous expression of Hh ligands, and is dependent upon the expression of Smoothened, an essential Hh response component that is not expressed in benign prostate epithelial cells. Monitoring and manipulating Hh pathway activity may thus offer significant improvements in diagnosis and treatment of prostate cancers with metastatic potential.