H2O2 has been the most commonly used inducer for stress-induced premature senescence (SIPS), which shares features of replicative senescence. However, there is still uncertainty whether SIPS and replicative senescence differ or utilize different pathways. 'Young' human diploid fibroblasts (HDFs), treated with prolonged low doses of hydrogen peroxide, led to irreversible cellular senescence. Cel...

When Detroit cells are infected with poliovirus in the presence of 5/~g./ml. of actinomycin, cell-controlled RNA synthesis is blocked and 2-[14C]uridine is incorporated only into poliovirus-specific RNA. The addition of polyinosinic-polycytidylic acid (5/%/ml.) under such conditions results in the inhibition of synthesis of 35s intracellular, infectious poliovirus RNA. A high molecular weight f...

Hematopoietic reconstitution after stem cell transplantation requires excessive replicative activity because of the limited number of stem cells that are used for transplantation. Telomere shortening has been detected in hematopoietic cells after bone marrow transplantation. This has been thought to result from excessive replication of the stem cells, with putative concomitant reduction of thei...

This paper is the first part of a trilogy, which comprises a detailed study of a special type of functional organization and demonstrates its relevance with respect to the origin and evolution of life. Self-replicative macromolecules, such as RNA or DNA in a suitable environment exhibit a behavior, which we may call Darwinian and which can be formally represented by the concept of the quasispec...

Half a century is fast approaching since Hayflick and colleagues formally described the limited ability of normal human cells to proliferate in culture (Hayflick and Moorhead, 1961). This finding – that normal somatic cells, in contrast to cancer cells, cannot divide indefinitely – challenged the prevailing idea that cells from mortal multicellular organisms were intrinsically ‘immortal’ (Carre...

OBJECTIVE Telomerase plays a major role in the control of replicative capacity, a critical property for successful angiogenesis and maintenance of endothelial integrity. In this study, we examined the relationship between telomerase activity and endothelial cell proliferation as well as the regulation of this enzyme by fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-A ...

The genotype-phenotype (GP) map is a central concept in evolutionary biology as it describes the mapping of molecular genetic variation onto phenotypic trait variation. Our understanding of that mapping remains partial, especially when trying to link functional clustering of pleiotropic gene effects with patterns of phenotypic trait co-variation. Only on rare occasions have studies been able to...

Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HI...

Several studies have shown that cytotoxic T lymphocytes (CTLs) play an important role in controlling HIV/SIV infection. Notably, the observation of escape mutants suggests a selective pressure induced by the CTL response. However, it remains difficult to assess the definite role of the cellular immune response. We devise a computational model of HIV/SIV infection having a broad cellular immune ...

Acquired human immunodeficiency virus type 1(HIV-1) resistance to the fusion inhibitor enfuvirtide (ENF) is primarily associated with mutations within the highly conserved first heptad repeat (HR1) region of gp41. Viral env sequences, however, are remarkably variable, and the envelope genetic background could have an important impact on optimal expression of HR1 mutations. We have examined the ...