Characterization of chimpanzee TCRV gene polymorphism: how old are human TCRV alleles?

 The functional relevance of the majority of human T-cell receptor A and B variable region gene polymorphisms is controversial. Studies of human and nonhuman primate major histocompatibility complex (MHC) class I and II polymorphisms show that allelic lineages predate human speciation and indicate that selection favors the long-term maintenance of these advantageous mutations. We investigated at the DNA level whether 15 human TCRA and B polymorphisms exist in contemporary chimpanzee populations. Polymorphisms consisted of variable region replacements, a recombination signal sequence base change, and silent mutations. With one exception, none of these human TCR polymorphisms were observed in contemporary chimpanzees. Investigation of the same polymorphisms in a range of other nonhuman primates showed little evidence of the existence of human polymorphism prespeciation. Chimpanzee TCRAV and BV regions were however polymorphic for variation so far not observed in human groups. Levels of mitochondrial and nuclear DNA sequence variation in contemporary chimpanzees suggest that population bottlenecks have not been a feature of chimpanzee evolution and it is therefore probable that most human TCR polymorphisms have evolved in the estimated five million years since the speciation of human and chimpanzees. Thus, over the evolutionary time period studied, ancient TCRA and B polymorphisms have not been maintained by selection to the same degree as postulated for MHC polymorphisms. Received: 13 June 1997 / Received: 25 July 1997     

Faulty old ideas about translational regulation paved the way for current confusion about how microRNAs function

Despite a recent surge of reports about how microRNAs might regulate translation, the question has not been answered. The proposed mechanisms contradict one another, and none is supported by strong evidence. This review explains some deficiencies in the experiments with microRNAs. Some of the problems are traceable to bad habits carried over from older studies of translational regulation, here illustrated by discussing two models involving mRNA binding proteins. One widely-accepted model, called into doubt by recent findings, is the maskin hypothesis for translational repression of cyclin B1 in Xenopus oocytes. The second dubious model postulates repression of translation of ceruloplasmin by mRNA binding proteins. A big fault in the latter case is reconstructing the imagined mechanism before looking carefully at the real thing--a criticism that applies also to studies with microRNAs. Experiments with microRNAs often employ internal ribosome entry sequences (IRESs) as tools, necessitating brief discussion of that topic. A sensitive new assay reveals that many putative IRESs promote expression of downstream cistrons via splicing rather than internal initiation of translation. Recent claims about the biological importance of IRES-binding proteins--including suggestions that these proteins might serve as targets for cancer therapy--are not supported by any meaningful evidence. The bottom line is that older studies of mRNA binding proteins and putative IRESs have created a confusing picture of translational regulation which is not helpful when trying to understand how microRNAs might work. The obvious biological importance of microRNAs makes it essential to understand how they do what they do. Fresh ways of thinking and looking are needed.     

Flavonols: old compounds for old roles

Background

New roles for flavonoids, as developmental regulators and/or signalling molecules, have recently been proposed in eukaryotic cells exposed to a wide range of environmental stimuli. In plants, these functions are actually restricted to flavonols, the ancient and widespread class of flavonoids. In mosses and liverworts, the whole set of genes for flavonol biosynthesis – CHS, CHI, F3H, FLS and F3′H – has been detected. The flavonol branch pathway has remained intact for millions of years, and is almost exclusively involved in the responses of plants to a wide array of stressful agents, despite the fact that evolution of flavonoid metabolism has produced >10 000 structures.

Scope

Here the emerging functional roles of flavonoids in the responses of present-day plants to different stresses are discussed based on early, authoritative views of their primary functions during the colonization of land by plants. Flavonols are not as efficient as other secondary metabolites in absorbing wavelengths in the 290–320 nm spectral region, but display the greatest potential to keep stress-induced changes in cellular reactive oxygen species homeostasis under control, and to regulate the development of individual organs and the whole plant. Very low flavonol concentrations, as probably occurred in early terrestrial plants, may fully accomplish these regulatory functions.

Conclusions

During the last two decades the routine use of genomic, chromatography/mass spectrometry and fluorescence microimaging techniques has provided new insights into the regulation of flavonol metabolism as well as on the inter- and intracellular distribution of stress-responsive flavonols. These findings offer new evidence on how flavonols may have performed a wide array of functional roles during the colonization of land by plants. In our opinion this ancient flavonoid class is still playing the same old and robust roles in present-day plants.     

From the backyard to the backcountry: how ecological and biological traits explain the escape of garden plants into Mediterranean old fields

To explain current ornamental plant invasions, or predict future ones, it is necessary to determine which factors increase the probability of an alien species becoming invasive. Here, we focused on the early phases of ornamental plant invasion in order to identify which plant features and cultivation practices may favor the escape of ornamental plants from domestic gardens to abandoned agricultural land sites in the Mediterranean Region. We used an original approach which consisted in visiting 120 private gardens in an urbanizing rural area of the French Mediterranean backcountry, and then visited surrounding old fields to determine which planted species had escaped out of the gardens. We built a database of 407 perennial ornamental alien species (most of which were animal-dispersed), and determined nineteen features that depicted the strength of species’ propagule pressure within gardens, the match between species requirements and local physical environment, and each species’ reproductive characteristics. Using standard and phylogenetic logistic regression, we found that ornamental alien plants were more likely to have escaped if they were planted in gardens’ margins, if they had a preference for dry soil, were tolerant to high-pH or pH-indifferent, and if they showed a capacity for clonal growth. Focusing only on animal-dispersed plants, we found that alien plants were more likely to have escaped if they were abundant in gardens and showed preference for dry soil. This suggests that gardening practices have a primary impact on the probability of a species to escape from cultivation, along with species pre-adaptation to local soil conditions, and capacity of asexual reproduction. Our results may have important implications for the implementation of management practices and awareness campaigns in order to limit ornamental plants to becoming invasive species in Mediterranean landscapes.     

Ubiquitin biology: an old dog learns an old trick

Regulated protein degradation in eukaryotes occurs principally through covalent tagging of substrates with ubiquitin, thereby targeting them for destruction by 26S proteasomes. Classical allostery has now been added to the repertoire of mechanisms that can modulate ubiquitin tagging, allowing feed-forward regulation to be achieved through targeted protein destruction.     

Evaluating how we evaluate

Evaluation of scientific work underlies the process of career advancement in academic science, with publications being a fundamental metric. Many aspects of the evaluation process for grants and promotions are deeply ingrained in institutions and funding agencies and have been altered very little in the past several decades, despite substantial changes that have taken place in the scientific work force, the funding landscape, and the way that science is being conducted. This article examines how scientific productivity is being evaluated, what it is rewarding, where it falls short, and why richer information than a standard curriculum vitae/biosketch might provide a more accurate picture of scientific and educational contributions. The article also explores how the evaluation process exerts a profound influence on many aspects of the scientific enterprise, including the training of new scientists, the way in which grant resources are distributed, the manner in which new knowledge is published, and the culture of science itself.     

Very old DNA

The verification of DNA sequences obtained from very old tissue sources as indeed ancient is a major point of discussion in the ancient DNA field. Proper controls and the use of the phylogenetic approach are the general methods employed for verification of the ancient DNA. Most studies have reported the recovery of extremely small amounts of nucleic acids which are sheared into rather small fragments. In addition, problems such as ‘PCR jumping’ can produce spurious sequence information. These observations suggest that random amplification techniques and the development of primers for highly informative but short target regions are essential for the further development of the ancient DNA field.     

Understanding how morphogens work

In this article, we describe the mechanisms by which morphogens in the Xenopus embryo exert their long-range effects. Our results are consistent with the idea that signalling molecules such as activin and the nodal-related proteins traverse responding tissue not by transcytosis or by cytonemes but by movement through the extracellular space. We suggest, however, that additional experiments, involving real-time imaging of morphogens, are required for a real understanding of what influences signalling range and the shape of a morphogen gradient.     

Antioxidant enzymes in erythrocytes from old and diet restricted old rats

Diet restriction, prolonging the lifespan of rodents, represents an interesting model for gerontological studies. We analyzed the activity of antioxidant enzymes, Superoxide Dismutase, Catalase and Glutathione Peroxidase in erythrocytes from young, old and old food restricted Wistar rats. Diet restriction was applied feeding the animals on every-other-day schedule starting from the age of 3.5 months. The age-dependent decrease of Catalase and Glutathione Peroxidase activities was prevented by food restriction, whereas Superoxide Dismutase activity was not influenced either by aging and dietary intervention. Present results support the hypothesis that diet restriction increases the protection of cell structure against the peroxidative damage, preserving the activity of antioxidant enzymes.     

The analgesia produced by food deprivation in 4-month old, 14-month old, and 24-month old rats

The analgesia produced by 24 hr of food deprivation was examined in 4-mo, 14-mo, and 24-mo old rats. To assess opioid and hormonal involvement in food deprivation induced analgesia, different groups of rats from each age group were injected with naltrexone (7 mg/kg), dexamethasone (0.4 mg/kg), or equivolume saline. Results revealed that food deprivation produced an equivalent analgesic response in each saline-treated age group. Also, naltrexone and dexamethasone were equally potent in blocking food deprivation induced analgesia in each age group. These results demonstrated that food deprivation activates an endogenous opioid-mediated analgesic system that involves hormonal factors and that this system does not change in function with increasing age.