The continuing evolution of weeds

Distinguished Economic Botanists’ address delivered 12 June 1990 at the 31st Annual Meeting of the Society for Economic Botany, University of Wisconsin, Madison (delayed publication resulting from illness of the author).     

ADHD in adults: a concept in evolution

Although attention-deficit/hyperactivity disorder (ADHD) has been recognized as a disorder affecting individuals across the life cycle since the end of the nineties, there is still considerable debate on how to conceptualize the disorder in adults, and on the best way to operationalize diagnostic criteria for this age range. In this comprehensive non-systematic review of the literature, we provide data about prevalence and presentation of ADHD in adulthood as well as discuss major problems in applying criteria developed for children in assessing adults (clinical utility, threshold of symptoms for diagnosis, full ADHD diagnosis in childhood, information source, and additional dimensions for diagnosis-executive functioning impairment and emotional impulsivity). In addition, we provide some recommendations for improving ADHD diagnostic criteria in adulthood.     

The concept of cellular evolution

Summary A central evolutionary question is whether the eucaryotic cytoplasm represents a line of descent that is separate from the typical bacterial line. It is argued on the basis of differences between their respective translation mechanisms that the two lines do represent separate phylogenetic trees in the sense that each line of descent independently evolved to a level of organization that could be called procaryotic. The two lines of descent, nevertheless shared a common ancestor, that was far simpler than the procaryote. This primitive entity is called a progenote, to recognize the possibility that it had not yet completed evolving the link between genotype and phenotype. This concept changes considerably the view one takes toward cellular evolution.     

The P2X7 receptor and intracellular pathogens: a continuing struggle

The purinergic receptor, P2X₇, has recently emerged as an important component of the innate immune response against microbial infections. Ligation of P2X₇ by ATP can stimulate inflammasome activation and secretion of proinflammatory cytokines, but it can also lead directly to killing of intracellular pathogens in infected macrophages and epithelial cells. Thus, while some intracellular pathogens evade host defense responses by modulating with membrane trafficking or cell signaling in the infected cells, the host cells have also developed mechanisms for inhibiting infection. This review will focus on the effects of P2X₇ on control of infection by intracellular pathogens, microbial virulence factors that interfere with P2X₇ activity, and recent evidence linking polymorphisms in human P2X₇ with susceptibility to infection.     

Ryanodine receptor mutations in arrhythmia: The continuing mystery of channel dysfunction

Mutations in RyR2 are causative of an inherited disorder which often results in sudden cardiac death. Dysfunctional channel behaviour has been the subject of many investigations varying from single channel analysis through to complex animal models. This review discusses recent advances in the field, describes the controversy surrounding the exact consequences of RyR2 mutation and how the disparate data may be reconciled. This heterogeneity of function with respect to the effects of polymorphisms, phosphorylation, cytosolic and luminal Ca²⁺ as well as inter-domain interactions may have important implications for the recent pharmaceutical therapies which have been put forward. We surmise that a comprehensive characterisation of mutations on a case-by-case basis may be beneficial for the development of specifically targeted therapies.     

Amphibian gastrulation: history and evolution of a 125 year-old concept.

The hypothetical gastraea concept, proposed by Haeckel (1874) to be an ancestral form common to all Metazoans, relied on the characterization of a gastrula stage in their embryonic development. The first steps that led to this characterization in Amphibian embryos fell into oblivion and deserve mention. Similarly, controversial debates about gastrula formation from the blastula, about simultaneous appearance of the three germ layers as opposed to a theoretical diploblastic embryo and about the occurrence of inward morphogenetic cell movements versus that of delamination processes, lasted for years. Following a half-century of polemic (1875-1925), Vogt's studies clearly and definitively established the reality and the complexity of morphogenetic movements, but this breakthrough long remained without further consequences. Holtfreter (1943,1944) illuminated unknown aspects of living gastrula cells and his observations helped to define many problems to be solved. During the second half of the 20th century, cell and molecular biology techniques, applied to the study of cell-cell and cell-matrix interactions, have brought new insights into the mechanisms of gastrula cell movements. Gene expression during these phenomena still remains an open question, as shown by a few recent studies: this situation strikingly contrasts with the many achievements that have been accomplished during the last decade in the analysis of induction phenomena during gastrulation.     

The concept of a changing receptor concentration: implications for the theory of drug action

Drugs are considered to produce their effects on biological tissues either by altering some physical property of cells or by interacting with specific cellular components, called receptors. Most drugs and endogenous neurotransmitters act on highly selective receptors located on the outer surface membrane of cells. These receptors were believed, until recently, to be stationary on the cell surface and to be present in unvarying numbers. Consequently, most early theorists modeled the drug-receptor interaction on the basis of stationary and static receptor molecules. The substantial advances in our understanding of drug action based on these models have partly justified this view. However, recent electron microscopic studies have revealed the presence of structures, including "coated" pits and vesicles, that appear to provide a mechanism by which cell surface receptors might be internalized in a process of endocytosis. The precise intracellular fate of these internalized receptors is unknown, but based on present understanding, it seems reasonable to believe that some are destroyed intracellularly whereas others are recycled to the cell surface. The importance of such processes to pharmacologic theory is a new awareness of a cellular pathway that is capable of internalizing drugs, receptors, or both. The implications of such a process to the theory of drug action extends to some unexplained drug phenomena such as down regulation, drug tolerance, tachyphyllaxis, and partial agonism. We present herein the theoretical framework for a model of drug action that incorporates the possibility of receptor internalization and subsequent degradation, recycling, or replacement.     

The structural evolution of a P2Y-like G-protein-coupled receptor

Based on the now available crystallographic data of the G-protein-coupled receptor (GPCR) prototype rhodopsin, many studies have been undertaken to build or verify models of other GPCRs. Here, we mined evolution as an additional source of structural information that may guide GPCR model generation as well as mutagenesis studies. The sequence information of 61 cloned orthologs of a P2Y-like receptor (GPR34) enabled us to identify motifs and residues that are important for maintaining the receptor function. The sequence data were compared with available sequences of 77 rhodopsin orthologs. Under a negative selection mode, only 17% of amino acid residues were preserved during 450 million years of GPR34 evolution. On the contrary, in rhodopsin evolution approximately 43% residues were absolutely conserved between fish and mammals. Despite major differences in their structural conservation, a comparison of structural data suggests that the global arrangement of the transmembrane core of GPR34 orthologs is similar to rhodopsin. The evolutionary approach was further applied to functionally analyze the relevance of common scaffold residues and motifs found in most of the rhodopsin-like GPCRs. Our analysis indicates that, in contrast to other GPCRs, maintaining the unique function of rhodopsin requires a more stringent network of relevant intramolecular constrains.     

The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping

The isolated retrograde-perfused Langendorff heart and the isolated ejecting heart have, over many decades, resulted in fundamental discoveries that form the underpinnings of our current understanding of the biology and physiology of the heart. These two experimental methodologies have proven invaluable in studying pharmacological effects on myocardial function, metabolism, and vascular reactivity and in the investigation of clinically relevant disease states such as ischemia-reperfusion injury, diabetes, obesity, and heart failure. With the advent of the genomics era, the isolated mouse heart preparation has gained prominence as an ex vivo research tool for investigators studying the impact of gene modification in the intact heart. This review summarizes the historical development of the isolated heart and provides a practical guide for the establishment of the Langendorff and ejecting heart preparations with a particular emphasis on the murine heart. In addition, current applications and novel methods of recording cardiovascular parameters in the isolated heart preparation will be discussed. With continued advances in methodological recordings, the isolated mouse heart preparation will remain physiologically relevant for the foreseeable future, serving as an integral bridge between in vitro assays and in vivo approaches.