The genetic basis and experimental evolution of inbreeding depression in Caenorhabditis elegans.

Determining the genetic basis of inbreeding depression is important for understanding the role of selection in the evolution of mixed breeding systems. Here, we investigate how androdioecy (a breeding system characterized by partial selfing and outcrossing) and dioecy (characterized by obligatory outcrossing) influence the experimental evolution of inbreeding depression in Caenorhabditis elegans. We derived inbred lines from ancestral and evolved populations and found that the dioecious lineages underwent more extinction than androdioecious lineages. For both breeding systems, however, there was selection during inbreeding because the diversity patterns of 337 single-nucleotide polymorphisms (SNPs) among surviving inbred lines deviated from neutral expectations. In parallel, we also followed the evolution of embryo to adult viability, which revealed similar starting levels of inbreeding depression in both breeding systems, but also outbreeding depression. Under androdioecy, diversity at a neutral subset of 134 SNPs correlated well with the viability trajectories, showing that the population genetic structure imposed by partial selfing affected the opportunity for different forms of selection. Our findings suggest that the interplay between the disruptions of coevolved sets of loci by outcrossing, the efficient purging of deleterious recessive alleles with selfing and overdominant selection with outcrossing can help explain mixed breeding systems.

The standard of neutrality: still flapping in the breeze?

Abstract Neutrality plays an important role as a null model in evolutionary biology. Recent theoretical advances suggest that neutrality is not a unitary concept, and we identify three distinct forms of neutrality. Eu-neutrality means that types do not differ in any measurable way and is thus the idealized form of neutrality. However, individuals or species that do differ in important ways can behave neutrally under some circumstances, both broadening and complicating the applicability of the concept of neutrality. Our second two types of neutrality address two quite different forms of context-dependent neutrality. Circum-neutrality means that two character states have the same direct effect on fitness but do not evolve neutrally because of differences in their circumstances. Iso-neutrality means that two types are equivalent in some population or ecological contexts but not in others, producing an isocline. Confounding of these different definitions has created significant confusion about which models are truly neutral, why some models behave neutrally even when there are large differences in reproductive outputs, and what these different views of neutrality mean to practicing biologists. These complications call into question the acceptance of neutral models as null models and suggest that a better approach is to compare the predictions of models that differ in sources of stochasticity and degree of selection.

[Regenerative medicine: stem cells, cellular and matricial interactions in the reconstruction of skin and cornea by tissue engineering]. / La médecine régénératrice : les cellules souches, les interactions cellulaires et matricielles dans la reconstruction cutanée et cornéenne par génie tissulaire.

Considering that there is a shortage of organ donor, the aim of tissue engineering is to develop substitutes for the replacement of wounded or diseased tissues. Autologous tissue is evidently a preferable transplant material for long-term graft persistence because of the unavoidable rejection reaction occuring against allogeneic transplant. For the production of such substitutes, it is essential to control the culture conditions for post-natal human stem cells. Furthermore, histological organization and functionality of reconstructed tissues must approach those of native organs. For self-renewing tissues such as skin and cornea, tissue engineering strategies must include the preservation of stem cells during the in vitro process as well as after grafting to ensure the long-term regeneration of the transplants. We described a tissue engineering method named the self-assembly approach allowing the production of autologous living organs from human cells without any exogenous biomaterial. This approach is based on the capacity of mesenchymal cells to create in vitro their own extracellular matrix and then reform a tissue. Thereafter, various techniques allow the reorganization of such tissues in more complex organ such as valve leaflets, blood vessels, skin or cornea. These tissues offer the hope of new alternatives for organ transplantation in the future. In this review, the importance of preserving stem cells during in vitro expansion and controlling cell differentiation as well as tissue organization to ensure quality and functionality of tissue-engineered organs will be discussed, while focusing on skin and cornea.

Anguilla rostrata glass eel migration and recruitment in the estuary and Gulf of St Lawrence.

This study describes catches of Anguilla rostrata glass eels and associated oceanographic conditions in the St Lawrence Estuary and Gulf. Ichthyoplankton survey data suggest that they enter the Gulf primarily in May, migrate at the surface at night, and disperse broadly once they have passed Cabot Strait. They arrive in estuaries beginning at about mid-June and through the month of July. Migration extends west up to Québec City, in the freshwater zone of the St Lawrence Estuary, 1000 km west of Cabot Strait. Anguilla rostrata glass eels travel between Cabot Strait and receiving estuaries at a straight-line ground speed of c. 10-15 km day(-1). Catches of fish per unit effort in estuaries in the St Lawrence system are much lower than those reported for the Atlantic coast of Canada. Low abundance of A. rostrata glass eels in the St Lawrence system may be due to cold surface temperatures during the migration period which decrease swimming capacity, long distances from the spawning ground to Cabot Strait and from Cabot Strait to the destination waters (especially the St Lawrence River), complex circulation patterns, and hypoxic conditions in bottom waters of the Laurentian Channel and the St Lawrence Estuary.

Rules of nonallelic noncomplementation at the synapse in Caenorhabditis elegans.

Nonallelic noncomplementation occurs when recessive mutations in two different loci fail to complement one another, in other words, the double heterozygote exhibits a phenotype. We observed that mutations in the genes encoding the physically interacting synaptic proteins UNC-13 and syntaxin/UNC-64 failed to complement one another in the nematode Caenorhabditis elegans. Noncomplementation was not observed between null alleles of these genes and thus this genetic interaction does not occur with a simple decrease in dosage at the two loci. However, noncomplementation was observed if at least one gene encoded a partially functional gene product. Thus, this genetic interaction requires a poisonous gene product to sensitize the genetic background. Nonallelic noncomplementation was not limited to interacting proteins: Although the strongest effects were observed between loci encoding gene products that bind to one another, interactions were also observed between proteins that do not directly interact but are members of the same complex. We also observed noncomplementation between genes that function at distant points in the same pathway, implying that physical interactions are not required for nonallelic noncomplementation. Finally, we observed that mutations in genes that function in different processes such as neurotransmitter synthesis or synaptic development complement one another. Thus, this genetic interaction is specific for genes acting in the same pathway, that is, for genes acting in synaptic vesicle trafficking.

Female choice via indicator traits easily evolves in the face of recombination and migration.

Species that exist in heterogeneous environments experience selection for specialization that is opposed by the homogenizing forces of migration and recombination. Migration tends to reduce associations between alleles and habitats, whereas recombination tends to break down associations among loci. The idea that heterogeneity should favor the evolution of isolating mechanisms has motivated evolutionary studies of reduced migration, habitat preference, and assortative mating. However, costly female choice of high-quality males can also evolve in heterogeneous populations and is not hindered by either recombination or migration. When information on male fitness is available through indicator traits, female choice based on these traits increases associations between female choice alleles and locally adapted alleles. Not only does female choice evolve in a heterogeneous environment, it acts to enhance the level of genetic variation and is thus self-reinforcing. The amount of female choice at equilibrium depends on how well mixed the habitats are, how much information on male genotype is available, and how different the habitats are. Female choice reaches the highest levels for intermediate levels of heterogeneity, because at such levels of heterogeneity there is both a high risk and high cost of mismating.

Can behavioural constraints alter the stability of signalling equilibria?

In traditional models of signalling one class of individual, the signaller, presents a signal which another class of individual, the receiver, examines. Receivers are typically assumed to have fitness returns that depend on their ability to determine the utility of the signaller to them. Each signaller must decide what level to signal at, which is a function of the quality of the signaller. In addition, a signaller's quality is assumed to be synonymous with the signaller's utility to a receiver. However, there is no reason to believe that signalling costs are incurred in the same currency as the receivers are paid and, thus, no reason to believe that the relationship between signaller quality and utility is linear or even increasing. For instance, in signalling between prey and predators, the utility of a prey item may be its fat reserves, whereas an individual prey pays for signalling (and thus measures quality) in terms of increased risk of capture; quality and utility are synonymous only if a high risk of capture is associated with high fat reserves. In addition, several recent studies have documented increased signalling as utility decreases. If utility and quality are decoupled, so that increasing quality does not always mean increasing utility, then traditional signalling models predict that no signalling equilibrium will exist. I show that if receiver fitness is modelled by a set of behavioural responses, which have both costs and benefits, then a signalling equilibrium can sometimes be recovered. An example of signalling between mates is presented in order to demonstrate this equilibrium.

Differential side effect profile of triazolam versus flurazepam in elderly patients undergoing rehabilitation therapy.

Patients (aged 65 years or older) who were hospitalized for rehabilitation therapy after a cerebrovascular accident or other acute debilitating condition participated in a 6-week controlled clinical trial. After a 2-week period of receiving nightly single-blind placebo, patients were randomly allocated to receive either triazolam (0.125 mg) or flurazepam hydrochloride (15 mg) nightly under double-blind conditions. For the final 2 weeks, patients again received single-blind placebo. The study groups' were comparable in their performance on four psychomotor tests done in the morning during the initial placebo period. Triazolam-treated patients showed subsequent improvement on the tests, consistent with practice effects, whereas flurazepam recipients showed performance impairment during treatment. Triazolam-flurazepam differences were significant in the card-sorting and arithmetic tests, and they approached significance for the Purdue pegboard test. Blind ratings by physical therapists indicated significant impairment among flurazepam recipients in their capacity to cooperate with and participate in the rehabilitation tasks; the impairment persisted into the post-treatment placebo period. Similar flurazepam-triazolam differences, although not significant, were reported by occupational therapy and nursing staff members. The findings suggest that the kinetic differences between flurazepam and triazolam may have clinical implications in elderly patients undergoing rehabilitation therapy.

Sources of stochasticity in models of sex allocation in spatially structured populations.

There are many ways to include stochastic effects in models of sex allocation evolution. These include variability in the number of mating partners and fecundity in a rich literature that goes back 20 years. The effects of variance in the fecundity and number of mating partners have typically been considered separately from the stochastic effects of mortality. However, I show that these processes produce mathematically equivalent models with subtly different biological details. These scenarios differ in the way that information becomes available to individuals because the parents often have information on mating partners while they are making sex allocation decisions, but must make these decisions before brood mortality takes place. This makes it possible to test which mechanism, stochastic mortality or variation in mating partners, is responsible for observed sex ratios. Alternatively, asymmetric variance between sexual functions can cause skewed sex allocation, even in the absence of local mate competition. This allows the evolution of either female- or male-biased sex ratios depending on which sexual function is more variable.

The ESS under spatial variation with applications to sex allocation.

I derive a new approximation which uses the backward Kolmogorov equation to describe evolution when individuals have variable numbers of offspring. This approximation is based on an explicit fixed population size assumption and therefore differs from previous models. I show that for individuals to accept an increase in the variance of offspring number, they must be compensated by an increase in mean offspring number. Based on this model and any given set of feasible alleles, an evolutionary stable strategy (ESS) can be found. Four types of ESS are possible and can be discriminated by graphical methods. These ESS values depend on population size, but population size can be reinterpreted as deme size in a structured population. I adapt this theory to the problem of sex allocation under variable returns to male and female function and derive the ESS sex allocation strategy. I show that allocation to the more variable sexual function should be reduced, but that this effect decreases as population size increases and as variability decreases. These results are compared with results from exact matrix models and computer simulations, all of which show strong congruence.

Survey of hospital systems and common serious medication errors.

The Institute for Safe Medication Practices and the University of Illinois at Chicago, College of Pharmacy, undertook a hospital survey of medical-surgical hospitals to determine systems-oriented factors that allow the highest level of medication safety. The study incorporated a peer-reviewed and pretested questionnaire, which focused on critical information necessary to yield quality data for comparison. Through analysis, it was shown that over one third of all medication errors reported in the survey involve just six categories--allergies, insulin, heparin, opiates, PCA devices, and potassium concentrates.

Medication error prevention: profiling one of pharmacy's foremost advocacy efforts for advice on error prevention.

Medication errors have become a growing concern with the increase in the number of critically ill patients, in the complexity of drug therapy and in the use of more potent, dangerous drugs. The Institute for Safe Medication Practices (ISMP), a nonprofit organization founded three years ago, is in the forefront of medication error prevention efforts. Working with practitioners, regulatory agencies, healthcare institutions, professional organizations and the pharmaceutical industry, both nationally and internationally, ISMP provides timely and accurate medication safety information through its educational programs, site-reviews, and ongoing publications. This article reviews the work of ISMP and offers recommendations for managers to begin error prevention strategies.