ABSTRACT
Humans are social animals whose well-being is shaped by the ability to attract and connect with one another, often through brief interactions. In addition to physical features, a choreography of movements, physical reactions and subtle expressions may help promote attraction. Here, we measured the physiological dynamics between pairs of participants during real-life dating interactions outside the laboratory. Participants wore eye-tracking glasses with embedded cameras and devices to measure physiological signals including heart rate and skin conductance. We found that overt signals such as smiles, laughter, eye gaze or the mimicry of those signals were not significantly associated with attraction. Instead, attraction was predicted by synchrony in heart rate and skin conductance between partners, which are covert, unconscious and difficult to regulate. Our findings suggest that interacting partners' attraction increases and decreases as their subconscious arousal levels rise and fall in synchrony.
Subject(s)
Arousal , Facial Expression , Animals , Arousal/physiology , Fixation, Ocular , Heart Rate/physiology , HumansABSTRACT
This study reports the successful introduction into tumor cells of a ribozyme directed against an oncogene using a retroviral gene delivery system. A hammerhead ribozyme that selectively targets and cleaves the activated Ha-ras (V12Ras) oncogene was delivered using a retroviral vector and expressed under the control of a transfer RNA promoter in V12Ras-transformed 3T3 murine fibroblast and rat colon epithelial cells. The expression of V12Ras messenger RNA and V12Ras P21 protein was reduced by up to 100% and 75%, respectively, in cells transduced with functional ribozyme. Reductions in V12Ras expression correlated with the stable expression of the functional ribozyme in vivo and decreased tumorigenicity in nude mice. Ribozyme constructs containing identical antisense flanking regions, but a mutant catalytic center, did not attenuate V12Ras expression or decrease the tumorigenicity of transduced tumor cells. These data support the potential therapeutic role of antioncogene ribozymes.
Subject(s)
Gene Expression Regulation, Neoplastic/physiology , Gene Transfer Techniques , Genes, ras , RNA, Catalytic/physiology , Retroviridae/genetics , 3T3 Cells , Animals , Cell Division/genetics , Mice , Mice, Nude , Neoplasms/genetics , Polymerase Chain Reaction , RatsABSTRACT
Arabinofuranosyl-5-azacytosine (Ara-AC), a new compound structurally related to arabinofuranosylcytosine (Ara-C) and 5-azacytidine (5-AC), has demonstrated significant therapeutic activity against a wide spectrum of murine tumors and three human tumor xenografts in the NCI tumor panel. Studies on the activity of Ara-AC in these and other human tumor xenograft models were undertaken to define its potential anti-human-tumor profile more completely. Ara-AC demonstrated marked antitumor activity against human tumor xenografts, including leukemias and solid tumors that do not respond to Ara-C or 5-AC. An important finding was the demonstration that Ara-AC was as effective by the oral route as when given intraperitoneally. Furthermore, the compound demonstrated synergism when combined with cisplatin in the treatment of refractory solid tumors and also induced monocyte-type differentiation of promyelocytic leukemia (HL-60) cells in vitro. Ara-AC is a promising new compound that may have utility in the treatment of human cancer beyond that anticipated for a cytotoxic nucleoside.
Subject(s)
Antineoplastic Agents/therapeutic use , Azacitidine/therapeutic use , Neoplasms/drug therapy , Animals , Cell Transformation, Neoplastic/drug effects , Cytarabine/therapeutic use , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Mice , Mice, Nude , Neoplasm Transplantation , Stereoisomerism , Time Factors , Transplantation, Heterologous , Tumor Cells, Cultured/drug effectsABSTRACT
A subline of human colon carcinoma cells (WiDr/R) resistant to the cytotoxic effects of mitoxantrone in vitro, was developed by continuous exposure to increasing concentrations of drug. After 16 culture passages in the presence of mitoxantrone, a cell population emerged which was 30-40 times more resistant to the cytolytic effect of mitoxantrone than the mitoxantrone-sensitive parent (WiDr/S) line. Resistance to mitoxantrone was retained by WiDr/R cells propagated for more than 40 cell generations in mitoxantrone-free medium. Decreased drug sensitivity was strongly associated with reduced intracellular accumulation of mitoxantrone. Moderate differences in drug retention by sensitive and resistant cells were demonstrated. However, decreased uptake due to alterations at the cell membrane which impair transport of drug into the cell, reducing interaction with DNA, appears to be the principal basis of resistance in these cells.
