Meiotic recombination: too much of a good thing?

Proper chromosome segregation in meiosis requires the right number and distribution of crossovers. Recent work in budding yeast has revealed a meiosis-specific role for RecQ helicase in limiting crossovers, distinct from its known somatic role in maintaining genome stability.     

p53 and ageing: too much of a good thing?

A recent report by Tyner et al.(1) suggests that p53 is bad for longevity. Heterozygotic mice carrying a p53 mutation that apparently enhances the stability of the wild-type protein showed shorter lifespans and faster ageing while also developing fewer tumours. This fits with the idea that cellular ageing is the price paid for better protection against unlimited proliferation of cancer cells. But other work shows that there is a strong positive association between DNA repair-mediated protection against cancer and ageing. So what are we to make of the new data with regard to overall understanding of the mechanisms of ageing?     

Tumour escape: antitumour effectors too much of a good thing?

Although even spontaneous tumours are immunogenic and are commonly infiltrated by tumour antigen-specific T cells (at least in melanoma), most tumours are not completely rejected by the host, and cancer progresses. There is a growing realisation that many responses defined as antitumour effector mechanisms act as double-edged swords and under different conditions either become ineffective or even protumorigenic. Examples are interleukin 2 (also proapoptotic for activated T cells), interferon (by induction of ligands for T and NK cell inhibitory receptors), angiogenesis inhibition (by hypoxia-mediated induction of growth factors promoting metastasis), and macrophage free radical-mediated cytotoxicity (by inhibiting T cells). Immune selection pressure itself, resulting in outgrowth of resistant tumour variants could also be viewed in this light. On the other hand, knowledge of the many tumour escape pathways offers the theoretical possibility of reconstituting antitumour immunity. Tumour escape from immunosurveillance represents the last series of hurdles to be overcome in formulating truly effective cancer immunotherapy, but given the immense plasticity of the tumour cell, and the complex balance between pro- and antitumour activity of the very same effector pathways, this remains a major challenge.This article is based on presentations made at the first Cancer Immunology and Immunotherapy Summer School, 8–13 September 2003, Ionian Village, Bartholomeio, Peloponnese, Greece.     

Salt intake in Amazonian ants: too much of a good thing?

Although herbivory is widespread among insects, plant tissues rarely provide the optimal balance of nutrients for insect growth and reproduction. As a result, many herbivorous insects forage elsewhere for particular amino acids and minerals. Recent studies have shown that both herbivory and recruitment to sodium are commonplace among tropical rainforest ants, but little is known about how ants regulate their sodium intake at the individual and colony levels. In social insects, foragers may respond not only to their own nutritional deficiencies but also to those of their nestmates, who may have different nutritional requirements depending on their developmental stage, sex, or caste. Here, we investigate how salt stress among rainforest ants affects their preferences for salt and subsequent survival. We found that ants recruited more to salt than to any other bait type tested, confirming the strong preference for salt of ants in this region. Initially, we observed similarly high recruitment to salt among workers of the arboreal, herbivorous/omnivorous ant species Camponotus mirabilis. However, when provided with unrestricted access to high concentrations of salt, C. mirabilis workers suffered significantly higher mortality relative to controls, suggesting that C. mirabilis workers forage for sodium to the point of toxicity. Nonetheless, surviving workers showed reduced preference for salt at the end of the experiment, so some but not all individuals were able to regulate their salt intake beneath lethal dosages. We discuss how salt intake regulation may depend on colony members other than workers.     

Complement-regulatory proteins in severe malaria: too little or too much of a good thing?

Data from several laboratories suggest that erythrocyte complement-regulatory proteins, in particular complement receptor 1 (CR1), are important in the pathogenesis of severe malaria. Additional studies suggest that the levels of expression of CR1 and the complement regulator CD55 on erythrocytes vary with age, being low in young children and increasing with age. It is proposed that the interplay between the rate at which immunity develops during malaria exposure and the changes in levels of erythrocyte complement-regulatory proteins that occur with age might contribute to the differences in epidemiology of severe malaria-associated anaemia and cerebral malaria.     

Subjectivity and flexibility in invasion terminology: too much of a good thing?

Invasions biologists have frequently debated whether the definition of invasive should include ecological and economic impacts. More recent criticisms posit that objective definitions are impossible in any absolute sense, while subjectivity is desirable for its flexibility and motivational qualities. We argue that such criticisms underestimate the extent of subjectivity already present in invasion biology. Ecological questions may be methodological if they relate directly to other ecological theories and models, or motivational if they focus on issues important to society as a whole. Motivational questions are important for engaging scientists, improving public understanding of science, and often have applied benefits. In contrast, methodological questions are constrained by established scientific theories, and are therefore more efficient for the development of scientific knowledge. Contrary to recent critiques, we suggest that greater objectivity is both achievable and desirable for the discipline of invasion biology and ecology generally.     

Alfy-dependent elimination of aggregated proteins by macroautophagy: Can there be too much of a good thing?

Degradation of different cargo by macroautophagy is emerging as a highly selective process which relies upon specific autophagy receptors and adapter molecules that link the cargo with the autophagic molecular machinery. We have recently reported that the large phsophatidylinositol-3-phosphate (PtdIns(3)P)-binding protein Alfy (Autophagy-linked FYVE protein) is required for selective degradation of aggregated proteins. Although depletion of Alfy inhibits Atg5-dependent aggregate degradation, overexpression of Alfy results in Atg5-dependent aggregate clearance and neuroprotection. Alfy-mediated degradation requires the ability of Alfy to directly interact with Atg5. This ability to interact with the core autophagic machinery may cause Alfy to diminish the responsiveness to nonselective autophagic degradation as measured by long-lived protein degradation. Thus, increasing Alfy-mediated protein degradation may be beneficial in some organs, but may be detrimental in others.Key words: autophagy, protein aggregates, neurodegeneration, Alfy, aggregation, degradation     

Mixed messages from multiple information sources on invasive species: a case of too much of a good thing?

Aim The increasing number and availability of online databases of alien species beg a question of their comparability given most do not adopt standard criteria in the definition of species status or taxonomic treatment and vary in their comprehensiveness. In this study, we compare the consistency of two major European databases for the regions they have in common. We assess whether they use consistent terminology to classify species status, provide similar taxonomic classification and coverage, deliver comparable estimates of alien richness per country and identify comparable correlates of alien richness. Location Northern Europe. Methods Data on the total number of alien species as well as the number of established alien species were extracted from the online databases DAISIE and NOBANIS for 13 European countries and classified into comparable taxonomic groups. Analyses across countries examined trends in alien species richness, correlations among taxonomic groups and the explanatory power of population density, country area and per capita GDP on alien species richness. Results Alien species richness, intertaxon correlations and the significance of individual drivers of invasion were all strongly database dependent. Differences were more marked for total numbers of aliens than established aliens. Over all taxonomic groups, DAISIE had lower species richness and fewer significant intertaxon correlations but presented a greater number of significant explanatory models of alien species richness. Trends in species richness were not generally correlated between the two databases with human population density being a more important driver in DAISIE while country area had greater explanatory power in NOBANIS. Main conclusions Considerable caution should be applied when collating data from different databases because often their underlying structure and content may differ markedly. For Europe, the analysis indicates that having two contrasting databases is not an ideal basis for implementing invasive species policy and moves should be made soon to establish a central pan‐European database.     

Too much of a good thing? Variety is confusing in mate choice

Choice variety is supposed to increase the likelihood that a chooser's preferences are satisfied. To assess the effects of variety on real-world mate choice, we analysed human dating decisions across 84 speed-dating events (events in which people go on a series of sequential 'mini-dates'). Results showed that choosers made fewer proposals (positive dating decisions) at events in which the available dates showed greater variety across such attributes as age, height, occupation and education, and this effect was particularly strong when choosers were confronted with a larger number of opposite-sex speed daters. Additionally, participants attending events in which the available options showed greater variety across these attributes were less likely to choose the consensually preferred mate option and more likely to choose no one at all. In contexts in which time is a limited resource, choice variety-rather than facilitating choice quality or increasing choosiness-is confusing and potentially detrimental to choice quality.     

Beta-carotene supplementation: a good thing, a bad thing, or nothing?

Available data from several completed large-scale randomized trials indicate that beta-carotene supplementation for durations up to 12 years has no overall benefit in well-nourished populations on the incidence of cardiovascular disease or the middle-to-late stages of carcinogenesis. Several important questions, however, remain unanswered. The post-trial follow-up of completed trials, together with the results of several ongoing trials of beta-carotene supplementation, will contribute reliable information to the totality of evidence from basic research, animal studies, observational epidemiologic studies, and completed trials, thus allowing more rational clinical decisions for individual patients and policy decisions for the health of the general public.     

Pediatric psychopharmacology: too much or too little?

This paper provides a selective overview of the past, present and future of pediatric psychopharmacology. The acceptance of medication use in child psychiatry was based on the results of double‐blind, placebo‐controlled trials documenting the efficacy of drug treatments for attention‐deficit/hyperactivity disorder, enuresis, depression, anxiety disorders, obsessive‐compulsive disorder and psychoses. This period of success was followed by a series of challenges, including a growing awareness of the long‐term adverse effects of medications and of the inadequacy of long‐term drug surveillance. There is great concern today that children are being overtreated with medication, especially in the US. Further advances in pediatric psychopharmacology may come from examination of large medical data sets including both pharmacological and psychiatric information, which could lead to drug repurposing, as well as from preclinical translational studies such as those using human induced pluripotent stem cells.     

Too much of a good thing? Finding the most informative genetic data set to answer conservation questions

Molecular markers are a useful tool allowing conservation and population managers to shed light on genetic processes affecting threatened populations. However, as technological advancements in molecular techniques continue to evolve, conservationists are frequently faced with new genetic markers, each with nuanced variation in their characteristics as well as advantages and disadvantages for informing various questions. We used a well‐studied population of Tasmanian devils (Sarcophilus harrisii) from Maria Island, Tasmania, to illustrate the issues associated with combining multiple genetic data sets and to help answer a question posed by many population managers: which data set will provide the most precise and accurate estimates of the population processes we are trying to measure? We analysed individual heterozygosity (as internal relatedness, IR) of 96 individuals, calculated using four genetic marker types (putatively neutral microsatellites, major histocompatibility complex‐linked microsatellites, reduced representation sequencing, and candidate region resequencing). We found no correlation in IR values across marker types, suggesting that various genetic markers reflect different aspects of genomic diversity. In addition, some marker types were more informative than others for conservation decision‐making. Reduced representation sequencing provided the highest precision (lowest error) for estimating population‐level genetic diversity, and most closely reflected genome‐wide heterozygosity both theoretically and empirically. Within the conservation context, our results highlight important considerations when choosing a molecular technique for wildlife genetics.     

Why change a good thing? Revisiting the fleur-de-lis reconstruction of the breast

Although the latissimus flap is known for its simplicity and reliability, use of the fleur-de-lis pattern was plagued by undesirable T-shaped donor sites and small breast volumes in thin patients. We report a modified technique for optimal shaping of the standard latissimus with the successful application of a modified fleur-de-lis pattern. Because a "wet" tumescent infiltration was utilized and large amounts of subcutaneous fat were harvested, these changes permitted application to a wide variety of patients, with generous breast volumes reducing the size of the implant placed and resulting in excellent donor-site scars.This is a retrospective cohort study of 53 delayed or immediate reconstructions performed consecutively by the principal author (M.E.A.) on 48 patients at a university-based, urban hospital. Each case was analyzed between April of 1995 and February of 1999, with a follow-up from 2.5 to 44 months. All patients underwent injection of tumescent solution into the subcutaneous plane and harvest of large amounts of subcutaneous fat with the neurologically intact latissimus muscle. The last 25 reconstructions utilized the modified fleur-de-lis skin pattern, an inferiorly based vertical limb and replacement of skin deficiency in both axes.Of 11 perioperatively irradiated patients, none required skin grafting, whereas 6 percent of all native mastectomy flaps were grafted. There was one instance of minor distal tip flap necrosis in a nonirradiated patient. No implants became infected or were extruded. Donor sites were without wound complications and unveiled a 16 percent overall seroma rate.Through selective addition of harvested tissue, this modified technique, particularly the fleur-de-lis pattern, permits improved volume and projection in the inferior pole. The T-shaped donor-site closure is not only acceptable, but is also desirable, with reduced wound tension and minimization of dog-ear formation. With a relative paucity of complications, this conceptually ideal modification is technically simple and aesthetically comparable to our transverse rectus abdominis muscle flap results.