Natural selection then and now

One often reads the following claims: (1) The modern conception of natural selection differs from Darwin's own conception only with respect to incidental features; (2) Natural selection is a very simple idea with enormous explanatory power. Both claims are problematic. R.A. Fisher famously argued that given a particulate view of inheritance, selection could proceed in a powerful manner even with frequent crossing, small fitness advantages and a low mutation rate. This is quite different from Darwin's view, which (roughly translated into a modern idiom) insists on infrequent crossing, large fitness advantages and a high mutation rate. The modern conception of natural selection is not the same as Darwin's, unless we describe natural selection in the most abstract manner. When so described, the ability of natural selection to account for adaptation is questionable.     

Seaweeds,then and now

An historical overview of meetings of the International Seaweed Symposium is presented. A summary of attempts since 1952 to establish a seaweed industry in British Columbia is given. A brief review of recent developments in the area in relation to a seaweed industry is outlined.     

The cell cycle: now live and in color

When observing living cells, only mitosis is easily distinguishable from other phases of the cell cycle. In this issue, Sakaue-Sawano et al. (2008) present a method to visually distinguish cells at different phases of the cell cycle by the expression of colored fusion proteins that are under the control of the ubiquitin ligases SCF and APC.     

Carcinogenicity and mutagenicity testing, then and now.

Cancer is a dread disease worldwide. Mortality of individuals suffering from cancer is high, despite the current improved methods of precocious detection, surgery and therapy. Prevention of cancer is the recognized goal of many activities in cancer research. This aim was recognized early to involve the bioassay of environmental chemicals or mixtures. The first such study involved application of coal tar to the ear of rabbits, and later on to the skin of mice. Subsequently, laboratory rats were introduced, and hamsters were utilized as a substitute for the unwieldy tests in rabbits. Investigators also became concerned with the mechanisms of carcinogenesis, and more definitive approaches to carcinogen bioassay in laboratory animals, as possible indicators of cancer risk in humans. These tests were expensive and lengthy, and did not serve the important purpose of accurately measuring risk of cancer to humans. Once it was realized that DNA and the genetic apparatus might be a key target, rapid bioassays in bacterial and mammalian cell systems were introduced successfully. Thus, batteries of tests are now available to detect effectively human cancer risks, and provide novel approaches to determine the underlying mechanisms, as a sound basis for cancer prevention.     

Proton pump inhibitory therapy: then and now.

Proton pump inhibitors (PPIs) have been established as the new "gold standard" for traditional acid-inhibitory treatment of the so called "peptic" diseases. Due to the high antisecretory and ulcer-healing potency of omeprazole, no major improvements of the efficacy in ulcer healing and pain relief can be expected. Pantoprazole, as a further development in PPIs, is characterized by improved pharmacokinetic behavior as well as by higher tissue selectivity and binding specificity and by a very low potential to interact with the cytochrome P450 enzyme system. These characteristics may provide the basis for a low potential for side effects and for a more favorable interaction profile, although the clinical relevance of these potential advantages remains to be proven. Reflux esophagitis will also remain a domain for the traditional use of PPIs in the future. However, in the treatment of gastroduodenal ulcers, the acid inhibitory potential of PPIs will be used mainly to facilitate the eradication of H. pylori.     

Inevitable glutathione,then and now

Glutathione a predominant tripeptide thiol compound of many prokaryotes and eukaryotes, is synthesized from its precursor amino acids eg. gamma-glutamate, cysteine and glycine. It is mainly involved in detoxication mechanisms through conjugation reactions. Other functions include thiol transfer, destruction of free radicals and metabolism of various exogenous and endogenous compounds. It becomes mandatory for a cell to manage high concentration of intracellular GSH to protect itself from chemical/dug abuse. Glutathione dependent enzymes viz: glutathione-S-transferases, glutathione peroxidase, glutathione reductase and gamma-glutamate transpeptidase facilitate protective manifestations. Liver serves as a glutathione-generating factor which supplies the kidney and intestine with other constituents of glutathione resynthesis. The principal mechanism of hepatocyte glutathione turnover appears to be cellular efflux. Kidney too plays an important role in organismic GSH homeostasis. Role of GSH in organs like lung, intestine and brain has recently been described. GSH involvement in programmed cell death has also been indicated. Immense interest makes the then "thee glutathione" as "inevitable glutathione". This article describes the role of this vital molecule in cell physiology and detoxication mechanisms in particular.     

Protein folding: then and now

Over the past three decades the protein folding field has undergone monumental changes. Originally a purely academic question, how a protein folds has now become vital in understanding diseases and our abilities to rationally manipulate cellular life by engineering protein folding pathways. We review and contrast past and recent developments in the protein folding field. Specifically, we discuss the progress in our understanding of protein folding thermodynamics and kinetics, the properties of evasive intermediates, and unfolded states. We also discuss how some abnormalities in protein folding lead to protein aggregation and human diseases.     

Anatomical terminology, then and now

Anatomical terminology, which had become chaotic by the nineteenth century, was codified in the BNA of 1895, when some 5,000 terms were carefully selected from among approximately 50,000 names. The BNA and its three major revisions (BR, INA, PNA) are here reviewed and placed in historical perspective. It is emphasized that many anatomical terms are very ancient and that the various nomenclatures are not 'new terminologies' but rather, for the most part, selections of already existing names. This can be seen clearly in the naming of the cranial nerves. Another example, the carpal and tarsal bones, is analysed in detail. Of the 8 carpal bones, for instance, the current names for 7 of them are those proposed by Henle in 1855. All the nomenclatures are, as they should be, in Latin, but it is understood that translations of many terms into other languages are necessary. Although views pro and con have been expressed, current usage favours the erect posture and the anatomical position as a basis, as well as the elimination of eponyms. In both teaching and research, the Nomina has been of great benefit in reducing drastically the number of unnecessary synonyms and in providing a coherent, internationally accepted system that is now the standard in anatomical textbooks. Hence, further use of the Nomina should be encouraged.     

The two-step model for translesion synthesis: then and now

The formation of base substitution mutations following exposure of bacteria to ultraviolet light and many other mutagens occurs during translesion synthesis opposite a photoproduct or other lesion in the template strand of DNA. This process requires the UmuD(2)' UmuC complex, only formed to a significant extent in SOS-induced cells. The "two-step" model proposed that there were two steps, insertion of a wrong base (misincorporation) and use of the misincorporated base as a primer for further chain extension (bypass). The original evidence suggested that UmuD(2)' UmuC was needed only for the second step and that in its absence other polymerases such as DNA polymerase III could make misincorporations. Now we know that the UmuD(2)' UmuC complex is DNA polymerase V and that it can carry out both steps in vitro and probably does both in vivo in wild-type cells. Even so, DNA polymerase III clearly has an important accessory role in vitro and a possibly essential role in vivo, the precise nature of which is not clear. DNA polymerases II and IV are also up-regulated in SOS-induced cells and their involvement in the broader picture of translesion synthesis is only now beginning to emerge. It is suggested that we need to think of the chromosomal replication factory as a structure through which the DNA passes and within which as many as five DNA polymerases may need to act. Protein-protein interactions may result in a cassette system in which the most appropriate polymerase can be engaged with the DNA at any given time. The original two-step model was very specific, and thus an oversimplification. As a general concept, however, it reflects reality and has been demonstrated in experiments with eukaryotic DNA polymerases in vitro.     

Transmembrane signaling,then and now: The decade of the eighties

The chronology of the major discoveries important in elucidating certain aspects of the molecular basis of transmembrane signaling is briefly reviewed. Recent developments linking cell stimulation and transformation are intimated.The author is the recipient of a Research Career Development Award (AI-00672) and a research grant (AI-28342) from the National Institute of Allergy and Infectious Diseases.