Inhibitors of the heat shock response: biology and pharmacology

A number of human diseases can be linked to aberrations in protein folding which cause an imbalance in protein homeostasis. Molecular chaperones, including heat shock proteins, act to assist protein folding, stability and activity in the cell. Attention has begun to focus on modulating the expression and/or activity of this group of proteins for the treatment of a wide variety of human diseases. This review will describe the progress made to date in developing pharmacological modulators of the heat shock response, including both agents which affect the entire heat shock response and those that specifically target the HSP70 and HSP90 chaperone families.     

Conceptual biology,hypothesis discovery,and text mining: Swanson's legacy

Innovative biomedical librarians and information specialists who want to expand their roles as expert searchers need to know about profound changes in biology and parallel trends in text mining. In recent years, conceptual biology has emerged as a complement to empirical biology. This is partly in response to the availability of massive digital resources such as the network of databases for molecular biologists at the National Center for Biotechnology Information. Developments in text mining and hypothesis discovery systems based on the early work of Swanson, a mathematician and information scientist, are coincident with the emergence of conceptual biology. Very little has been written to introduce biomedical digital librarians to these new trends. In this paper, background for data and text mining, as well as for knowledge discovery in databases (KDD) and in text (KDT) is presented, then a brief review of Swanson's ideas, followed by a discussion of recent approaches to hypothesis discovery and testing. 'Testing' in the context of text mining involves partially automated methods for finding evidence in the literature to support hypothetical relationships. Concluding remarks follow regarding (a) the limits of current strategies for evaluation of hypothesis discovery systems and (b) the role of literature-based discovery in concert with empirical research. Report of an informatics-driven literature review for biomarkers of systemic lupus erythematosus is mentioned. Swanson's vision of the hidden value in the literature of science and, by extension, in biomedical digital databases, is still remarkably generative for information scientists, biologists, and physicians.     

The biology of the heat shock response in parasites

The heat shock response is a general homeostatic mechanism that protects cells and the entire organism from the deleterious effects of environmental stress. It has been shown that heat shock proteins play major roles in many cellular processes and have a unique role in several areas of cell biology, from chronic degenerative diseases to immunology and from cancer research to interactions between host and parasite. In this review, Bruno Maresca and Luisella Carratu deal with some of the unique characteristics of the heat shock response in parasitic organisms.     

Science and society: Asilomar and after: A decade of the new biology

In February 1975, in Pacific Grove, California, the Asilomar Conference took place, sponsored by the U.S. National Academy of Sciences and convened by the Academy's Committee on Recombinant DNA Molecules, of which Paul Berg was the Chairman. This conference recommended guidelines for recombinant DNA research, and the history of subsequent sets of guidelines formed the major theme of six articles that appeared in Vol. 1 of BioEssays, authored by Dewitt Stetten, Jr, with the collaboration of William Gartland and Bernard Talbot and entitled ‘The Road to Asilomar: Reminiscences of the Recombinant DNA Story’.¹ The U.S. National Research Council recently commissioned for its News Report (volume XXXV, March 1985, 1A–16A) a retrospective article on Asilomar, written by Susan Walton. That article is exerpted here with the permission of the National Research Council.     

The interferons: 50 years after their discovery, there is much more to learn

The interferons (IFNs) and their receptors represent a subset of the class 2 alpha-helical cytokines that have been in chordates for millions of years. This brief review focuses on the discovery and purification of interferons, cloning of human IFN-alpha and IFN-beta, interferon receptors, activities and therapeutic uses of interferons, and the side effects of interferons.     

Structure,properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding–unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA–RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.     

Double helix of the journal Cytology and Genetics: 50 years later

This survey paper contains a brief analysis of publications included in the current issue of the scientific journal Cytology and Genetics dedicated to its 50th anniversary. These papers reflect scientific achievements of their authors in the field of genetics and cell biology and underline the potential of these two biological disciplines, forming the double helix of the journal.     

Characterization of the heat shock response in cultured sugarcane cells : I. Physiology of the heat shock response and heat shock protein synthesis

Effect of heat shock on the growth of cultured sugarcane cells (Saccharum officinarum L.) was measured. Heat shock (HS) treatment at 36 to 38°C (2 hours) induced the development of maximum thermotolerance to otherwise nonpermissive heat stress at 54°C (7 minutes). Optimum thermotolerance was observed 8 hours after heat shock. Development of thermotolerance was initiated by treatments as short as 30 minutes at 36°C. Temperatures below 36°C or above 40°C failed to induce maximum thermotolerance. In vivo labeling revealed that HS at 32 to 34°C induced several high molecular mass heat shock proteins (HSPs). A complex of 18 kilodalton HSPs required at least 36°C treatment for induction. The majority of the HSPs began to accumulate within 10 minutes, whereas the synthesis of low molecular mass peptides in the 18 kilodalton range became evident 30 minutes after initiation of HS. HS above 38°C resulted in progressively decreased HSP synthesis with inhibition first observed for HSPs larger than 50 kilodaltons. Analysis of two-dimensional gels revealed a complex pattern of label incorporation including the synthesis of four major HSPs in the 18 kilodalton range and continued synthesis of constitutive proteins during HS.     

Morphogenesis after heat shock during the cell cycle ofLymnaea: A new interpretation

Summary The effect of a heat shock (37.0–38.0°C, 10 min) during the third and fourth cleavage cycles ofLymnaea was investigated. The sensitivity with respect to the duration of the cell cycle and morphogenesis appeared to be periodic. The cycle extension curve has three maxima: at the beginning of the cycle, at the G₂-phase, and at prometaphase. With regard to morphogenesis, the eggs become sensitive shortly before cleavage, when cleavage cannot be delayed any more.In eggs treated at the morphogenetically sensitive stages, mitotic abnormalities caused by an incomplete separation of the chromosomes during treatment were observed. Some cells were lethally affected, and the division chronology was abnormal in some embryos.It is concluded that heat shock disturbs a process relevant to the cell cycle. If applied before metaphase, an extension of the cell cycle permits a complete recovery and morphogenesis remains unaffected. If applied at metaphase or later, cell division is not delayed, but mitosis is seriously disturbed. This irreversible damage is the cause of abnormal morphogenesis. The type of malformation depends on the prospective significance of the affected blastomeres.