Walter and Eliza Hall Institute of Medical Research

About: Walter and Eliza Hall Institute of Medical Research is a nonprofit organization based out in Melbourne, Victoria, Australia. It is known for research contribution in the topics: Antigen & Immune system. The organization has 5012 authors who have published 10620 publications receiving 873561 citations.

The granulocyte-macrophage colony-stimulating factors.

Abstract: The granulocyte-macrophage colony-stimulating factors are well-characterized specific glycoproteins that interact to control the production, differentiation, and function of two related white cell populations of the blood, the granulocytes and monocyte-macrophages. Widely produced in the body, these regulators probably play an important role in resistance to infections. The proliferation of myeloid leukemia cells remains dependent on stimulation by colony-stimulating factors, although one of them also has the ability to suppress leukemic populations by inducing terminal differentiation.

Moderated statistical tests for assessing differences in tag abundance

Abstract: Motivation: Digital gene expression (DGE) technologies measure gene expression by counting sequence tags. They are sensitive technologies for measuring gene expression on a genomic scale, without the need for prior knowledge of the genome sequence. As the cost of sequencing DNA decreases, the number of DGE datasets is expected to grow dramatically. Various tests of differential expression have been proposed for replicated DGE data using binomial, Poisson, negative binomial or pseudo-likelihood (PL) models for the counts, but none of the these are usable when the number of replicates is very small. Results: We develop tests using the negative binomial distribution to model overdispersion relative to the Poisson, and use conditional weighted likelihood to moderate the level of overdispersion across genes. Not only is our strategy applicable even with the smallest number of libraries, but it also proves to be more powerful than previous strategies when more libraries are available. The methodology is equally applicable to other counting technologies, such as proteomic spectral counts. Availability: An R package can be accessed from http://bioinf.wehi.edu.au/resources/ Contact: smyth@wehi.edu.au Supplementary information: http://bioinf.wehi.edu.au/resources/

Pgh1 modulates sensitivity and resistance to multiple antimalarials in Plasmodium falciparum.

Abstract: Throughout the latter half of this century, the development and spread of resistance to most front-line antimalarial compounds used in the prevention and treatment of the most severe form of human malaria has given cause for grave clinical concern. Polymorphisms in pfmdr1, the gene encoding the P-glycoprotein homologue 1 (Pgh1) protein of Plasmodium falciparum, have been linked to chloroquine resistance1; Pgh1 has also been implicated in resistance to mefloquine and halofantrine2,3,4,5. However, conclusive evidence of a direct causal association between pfmdr1 and resistance to these antimalarials has remained elusive, and a single genetic cross has suggested that Pgh1 is not involved in resistance to chloroquine and mefloquine6. Here we provide direct proof that mutations in Pgh1 can confer resistance to mefloquine, quinine and halofantrine. The same mutations influence parasite resistance towards chloroquine in a strain-specific manner and the level of sensitivity to the structurally unrelated compound, artemisinin. This has important implications for the development and efficacy of future antimalarial agents.

Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease

Abstract: The biological functions of the BCL2 gene were investigated in transgenic mice harboring human BCL2 cDNA under the control of an immunoglobulin heavy chain enhancer (E mu). Mice of a representative transgenic strain, E mu-bcl-2-22, had a great excess of B lymphocytes, immunoglobulin-secreting cells, and serum immunoglobulins, attributable to increased longevity of B-lineage cells. Pre-B and plasma cells as well as B cells exhibited prolonged survival in culture. Immunized animals produced an amplified and protracted antibody response. Within the first year of life, most mice spontaneously produced antibodies to nuclear antigens, and 60% developed kidney disease, diagnosed as immune complex glomerulonephritis. Thus E mu-bcl-2-22 mice constitute a transgenic model for a systemic autoimmune disease resembling the human disorder systemic lupus erythematosus.