Despite the effectiveness of currently available human immunodeficiency virus type 1 (HIV-1) therapies, a continuing need exists for new drugs to treat HIV-1 infection. We investigated the mechanism by which 3-O-[3',3'-dimethylsuccinyl]-betulinic acid (DSB) inhibits HIV-1 replication. DSB functions at a late stage of the virus life cycle but does not inhibit the HIV-1 protease in vitro or inter...

Introduction: A high risk for development of severe side effects after radiotherapy may be correlated with high cellular radiosensitivity. To enhance radiation therapy efficiency a fast and reliable in-vitro test is desirable to identify radiosensitive patients. The aim of present study was to identify the mechanism of radiation induced DNA double-strand breaks (DSBs) and DSB r...

BACKGROUND Understanding suicidal behavior is an important component of assessing suicidality in psychiatric patients. GlaxoSmithKline (GSK) conducted a meta-analysis of randomized, placebo-controlled trials to compare suicidality in adult patients treated with paroxetine vs. placebo. The goal was to identify emergent clinical characteristics of patients with definitive suicidal behavior (DSB: ...

background: immunotoxins are comprised of both the cell targeting and the cell killing moieties. we previously established a new immunotoxin, i.e. shiga toxin granulocyte macrophage-colony stimulating factor (stxa1-gm-csf), comprises of catalytic domain of stx, as a killing moiety and gm-csf, as a cell targeting moiety. in this study, the ability of the immunotoxin to induce apoptosis and doubl...

Differences in ex vivo cell culture conditions can drastically affect stem cell physiology. We sought to establish an assay for measuring the effects of chemical, environmental, and genetic manipulations on the precision of repair at a single DNA double-strand break (DSB) in pluripotent and somatic human cells. DSBs in mammalian cells are primarily repaired by either homologous recombination (H...

Fibroblasts from patients with the severe laminopathy diseases, restrictive dermopathy (RD) and Hutchinson Gilford progeria syndrome (HGPS), are characterized by poor growth in culture, the presence of abnormally shaped nuclei and the accumulation of DNA double-strand breaks (DSB). Here we show that the accumulation of DSB and poor growth of the fibroblasts but not the presence of abnormally sh...

Wortmannin, an inhibitor of p110 PI 3-kinase, also inhibits DNA-dependent protein kinase, which is known to mediate DNA double strand break repair. It was recently demonstrated that wortmannin sensitized cells to ionizing radiation (IR) (Price and Youmell, Cancer Res., 56, 246-250, 1996). Wortmannin was used to determine if the potentiation of IR-induced cytotoxicity in Chinese hamster ovary ce...

A novel microwave photonic true-time-delay (TTD) system using carrier compensation technology is proposed and experimentally demonstrated. Wavelength division multiplexing combines ten lasers into a single beam. We separate one channel from the laser as compensating carrier, combined with time-delayed optical signals to be detected. Meanwhile, sideband are amplified effectively thanks carrier-s...

53BP1 is a key component of the genome surveillance network activated by DNA double strand breaks (DSBs). Despite its known accumulation at the DSB sites, the spatiotemporal aspects of 53BP1 interaction with DSBs and the role of other DSB regulators in this process remain unclear. Here, we used real-time microscopy to study the DSB-induced redistribution of 53BP1 in living cells. We show that w...

PURPOSE To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. METHODS AND MATERIALS The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related norm...