DNA and the chromosome – varied targets for chemotherapy

The nucleus of the cell serves to maintain, regulate, and replicate the critical genetic information encoded by the genome. Genomic DNA is highly associated with proteins that enable simple nuclear structures such as nucleosomes to form higher-order organisation such as chromatin fibres. The temporal association of regulatory proteins with DNA creates a dynamic environment capable of quickly responding to cellular requirements and distress. The response is often mediated through alterations in the chromatin structure, resulting in changed accessibility of specific DNA sequences that are then recognized by specific proteins. Anti-cancer drugs that target cellular DNA have been used clinically for over four decades, but it is only recently that nuclease specific drugs have been developed to not only target the DNA but also other components of the nuclear structure and its regulation. In this review, we discuss some of the new drugs aimed at primary DNA sequences, DNA secondary structures, and associated proteins, keeping in mind that these agents are not only important from a clinical perspective but also as tools for understanding the nuclear environment in normal and cancer cells

Quick Start Guide to Soil Methods for Ecologists

Increasingly biologists and ecologists are becoming aware of the vital importance of soil to processes observed above ground and are incorporating soil analyses into their research. Because of the dynamic and heterogeneous nature of soil, proper incorporation of soil analysis into ecological studies requires knowledge and planning. Unfortunately, many ecologists may not be current (or trained at all) in soil science.We provide this review, based on our cumulative \u3e60 years of work in soil science,to help familiarize researchers with essential information to appropriately incorporate soil analyses into ecological studies. Specifically, we provide a brief introduction into soils and then discuss issues related to soil sterilization, choosing a soil for a greenhouse project, sampling soils, and soil analyses

Ancient expansion of the Hox cluster in Lepidoptera generated four homeobox genes implicated in extra-embryonic tissue formation

Gene duplications within the conserved Hox cluster are rare in animal evolution, but in Lepidoptera an array of divergent Hox-related genes (Shx genes) has been reported between pb and zen. Here, we use genome sequencing of five lepidopteran species (Polygonia c-album, Pararge aegeria, Callimorpha dominula, Cameraria ohridella, Hepialus sylvina) plus a caddisfly outgroup (Glyphotaelius pellucidus) to trace the evolution of the lepidopteran Shx genes. We demonstrate that Shx genes originated by tandem duplication of zen early in the evolution of large clade Ditrysia; Shx are not found in a caddisfly and a member of the basally diverging Hepialidae (swift moths). Four distinct Shx genes were generated early in ditrysian evolution, and were stably retained in all descendent Lepidoptera except the silkmoth which has additional duplications. Despite extensive sequence divergence, molecular modelling indicates that all four Shx genes have the potential to encode stable homeodomains. The four Shx genes have distinct spatiotemporal expression patterns in early development of the Speckled Wood butterfly (Pararge aegeria), with ShxC demarcating the future sites of extraembryonic tissue formation via strikingly localised maternal RNA in the oocyte. All four genes are also expressed in presumptive serosal cells, prior to the onset of zen expression. Lepidopteran Shx genes represent an unusual example of Hox cluster expansion and integration of novel genes into ancient developmental regulatory networks

Information retention and overload in first-time hearing aid users: an interactive multimedia educational solution

Purpose: An educational intervention to improve knowledge of hearing aids and communication in first-time hearing aid users was assessed. This intervention was based on the concept of reusable learning objects (RLOs). Method: A randomized controlled trial was conducted. One group received the educational intervention, and the other acted as a control group. RLOs were delivered online and through DVD for television and personal computer. Knowledge of both practical and psychosocial aspects of hearing aids and communication was assessed using a free-recall method 6 weeks postfitting. Results: Knowledge of both practical and psychosocial issues was significantly higher in the group that received the RLOs than in the control group. Moderate to large effect sizes indicated that these differences were clinically significant. Conclusion: An educational intervention that supplements clinical practice results in improved knowledge in first-time hearing aid users

Tissue oxygenation with graded dissolved oxygen delivery during cardiopulmonary bypass

AbstractBackground: Intravascular perfluorochemical emulsions together with a high oxygen tension may increase the delivery of dissolved oxygen to useful levels. The hypothesis of this study is that increasing the dissolved oxygen content of blood with incremental doses of a perfluorochemical emulsion improves tissue oxygenation during cardiopulmonary bypass in a dose-related fashion. Methods and Results: Oxygen utilization was studied in a profoundly anemic canine model of hypothermic cardiopulmonary bypass. Forty-two dogs (mean ± standard error of the mean). Cardiopulmonary bypass was begun and resulted in a hematocrit of 9.4% + 0.6%. A standard primng solution was used in the control group (n = 12), and the test groups received 1.35 gm perfluorochemical · kg-1 (n = 10 dogs), or 5.4 gm perfluorochemical · kg-1 (n = 10 dogs), 2.7 gm perfluorochemical · kg-1(n = 10 dogs) through the venous return cannula. Each animal underwent a series of randomized pump flows (0.25,0.5, 1.0, 1.5, 2.0, and 3.0 L · min-1 · m-2 ) at 32° C. After the randomized flows were completed at 32° C, the temperature was raised to 38° C and cardiopulmonary bypass was discontinued. Mortality from cardiac failure on separation from cardiopulmonary bypass was 42% in the control group and 20% in perfluorochemical-treated groups. The mean perfluorochemical dose was higher in surviviors than in nonsurvivors (2.9 + 0.4 versus 1.3 + 0.5 gm perfluorochemical · kg-1; p < 0.05). No differences in oxygen consumption or transbody lactate gradient were found between groups during cardiopulmonary bypass. Analysis of mixed venous oxygen tension (a surrogate measure for tissue oxygenation) as a function of cardiopulmonary bypass flow normalized to body surface area showed that the control group had significantly lower mixed venous oxygen tension (p < 0.05) than the perfluorochemical emulsion-treated groups. Furthermore, the differences were related to the perfluorochemical emulsion dose. These differences in mixed venous oxygen tension continued after termination of cardiopulmonary bypass. The coronary sinus oxygen tension and cardiac arterial-venous oxygen content differences during and after cardiopulmonary bypass were similar among the control and perfluorochemical emulsion-treated animals. Dissolved oxygen consumption during and after cardiopulmonary bypass was calculated. Dissolved oxygen consumption increased in the perfluorochemical-treated animals in a perfluorochemical dose-related manner and was significantly higher in perfluoro-chemical-treated animals than in the control animals (p < 0.05). Conclusions: Graded increases in mixed venous oxygen tension during cardiopulmonary bypass were observed in response to graded increases in the dissolved oxygen delivery. These data suggest that enhancing oxygenation with perfluorochemical-dissolved oxygen is an effective temporary substitute for the use of hemoglobin-bound oxygen during cardiopulmonary bypass. Perfluorochemical-dissolved oxygen may be particularly beneficial in the setting of multiple hypoxic stresses. (J THORAC CARDIOVASC SURG 1995;110: 774-85)J THORAC CARDIOVASC SURG 1995;110:1-85