Human immunodeficiency virus induces phosphorylation of its cell surface receptor

AIDS is an immunoregulatory disorder characterized by depletion of the CD4+, helper/inducer lymphocyte population. The causative agent of this disease is the human immunodeficiency virus, HIV, which infects CD4+ cells and leads to cytopathic effects characterized by syncytia formation and cell death. Recent studies have demonstrated that binding of HIV to its cellular receptor CD4 is necessary for viral entry. We find that binding of HIV to CD4 induces rapid and sustained phosphorylation of CD4 which could involve protein kinase C. HIV-induced CD4 phosphorylation can be blocked by antibody against CD4 and monoclonal antibody against the HIV envelope glycoprotein gp120, indicating that a specific interaction between CD4 and gp120 is required for phosphorylation. Electron microscopy shows that a protein kinase C inhibitor does not impair binding of HIV to CD4+ cells, but causes an apparent accumulation of virus particles at the cell surface, at the same time inhibiting viral infectivity. These results indicate a possible role for HIV-induced CD4 phosphorylation in viral entry and identify a potential target for antiviral therapy.     

公寓建筑中自然通风的潜在利用

该研究旨在检验在公寓建筑中自然通风的潜在利用对机械通风系统换气率的影响，以便提出适当的关于换气率的建议，现场测量在13栋公寓单元进行．测量时住宅内外的压力差有所变化．采用实测数据，对4Pa压力差下的换气率提出预测，换气率在每小时0．18～0，41间变化．     

On the radioactivity of certain stable isotope-enriched substances

Résumé Des mesures de radioactivité de nombreux échantillons d'eau lourde et de substances deutérées de provenances les plus diverses ont montré que les substances de teneur élevée en deutérium (>99%) présentent une radioactivité spécifique de l'ordre de 5 µCi par gramme de deutérium, due au tritium d'origine naturelle concentré en meme temps que le deutérium. Le phénomène ne se limite pas aux isotopes de l'hydrogène. Il est de caractère général et comporte d'importances conséquences théoriques et pratiques.

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Financial support by the Swiss National Foundation for Scientific Research is acknowledged.     

Compensatory caspase activation in MPP+-induced cell death in dopaminergic neurons

Many have hypothesized that cell death in Parkinsons disease is via apoptosis and, specifically, by the mitochondrial-mediated apoptotic pathway. We tested this hypothesis using a mouse dopaminergic cell line of mesencephalic origin, MN9D, challenged with the Parkinsonism-causing neurotoxin MPP⁺ (1-methyl-4-phenylpyridinium ion). Apoptosis was the main mode of cell death when the cells were subjected to MPP⁺ treatment under serum-free conditions for 24 h. Caspase-3 and caspase-9, however, were not activated, thus indicating the existence of alternate or compensatory cell death pathway(s) in dopaminergic neuronal cells. Using caspase inhibitors, we demonstrated that these pathways involve caspase-2, –8, –6 and –7. A time-course study indicated that activation of caspase-2 and –8 occurred upstream of caspase-6 and caspase-7. Upon MPP⁺ challenge, the apoptosis-inducing factor was translocated from the mitochondria into the MN9D cytosol and nucleus. These results suggest the existence of alternative apoptotic pathways in dopaminergic neurons.Received 20 September 2004; received after revision 5 November 2004; accepted 22 November 2004     

Ambivalent effect of protein binding on computed distributions of metal ions complexed by ligands in blood plasma

Summary Although the absolute concentrations of metal complexes in blood plasma are controlled by protein binding, the percentage distribution of transition metal ions amongst low molecular weight ligands is not. Thus, computer simulations which omit protein equilibria can nevertheless afford reliable information about such metals in the biofluid.Acknowledgments. One of us (P. M. M.) thanks the University of Cape Town and the C. S. I. R. for financial assistance. Computations were performed on both of the University of Cape Town's UNIVAC 1106 system and the St. Andrews University's IBM 360/44. Address ofP. W. Linder: University of Cape Town, Rondebosch, Cape (South Africa).