Impact of demography on extinction/fixation events

In this article we consider diffusion processes modeling the dynamics of multiple allelic proportions (with fixed and varying population size). We are interested in the way alleles extinctions and fixations occur. We first prove that for the Wright–Fisher diffusion process with selection, alleles get extinct successively (and not simultaneously), until the fixation of one last allele. Then we introduce a very general model with selection, competition and Mendelian reproduction, derived from the rescaling of a discrete individual-based dynamics. This multi-dimensional diffusion process describes the dynamics of the population size as well as the proportion of each type in the population. We prove first that alleles extinctions occur successively and second that depending on population size dynamics near extinction, fixation can occur either before extinction almost surely, or not. The proofs of these different results rely on stochastic time changes, integrability of one-dimensional diffusion processes paths and multi-dimensional Girsanov’s tranform.

     

Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans

Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively.     

Seleno-independent glutathione peroxidases. More than simple antioxidant scavengers

Glutathione peroxidases (GPXs, EC 1.11.1.9) were first discovered in mammals as key enzymes involved in scavenging of activated oxygen species (AOS). Their efficient antioxidant activity depends on the presence of the rare amino-acid residue selenocysteine (SeCys) at the catalytic site. Nonselenium GPX-like proteins (NS-GPXs) with a Cys residue instead of SeCys have also been found in most organisms. As SeCys is important for GPX activity, the function of the NS-GPX can be questioned. Here, we highlight the evolutionary link between NS-GPX and seleno-GPX, particularly the evolution of the SeCys incorporation system. We then discuss what is known about the enzymatic activity and physiological functions of NS-GPX. Biochemical studies have shown that NS-GPXs are not true GPXs; notably they reduce AOS using reducing substrates other than glutathione, such as thioredoxin. We provide evidence that, in addition to their inefficient scavenging action, NS-GPXs act as AOS sensors in various signal-transduction pathways.     

Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart

Heart failure is a consequence of progressive deterioration of cardiac performance. Little is known about the role of impaired oxidative phosphorylation in the progression of the disease, since previous studies of mitochondrial injuries are restricted to end-stage chronic heart failure. The present study aimed at evaluating the involvement of mitochondrial dysfunction in the development of human heart failure. We measured the control of oxidative phosphorylation with high-resolution respirometry in permeabilized myocardial fibres from donor hearts (controls), and patients with no or mild heart failure but presenting with heart disease, or chronic heart failure due to dilated or ischemic cardiomyopathy. The capacity of the phosphorylation system exerted a strong limitation on oxidative phosphorylation in the human heart, estimated at 121 pmol O(2)s(-1)mg(-1) in the healthy left ventricle. In heart disease, a specific defect of the phosphorylation system, Complex I-linked respiration, and mass-specific fatty acid oxidation were identified. These early defects were also significant in chronic heart failure, where the capacities of the oxidative phosphorylation and electron transfer systems per cardiac tissue mass were decreased with all tested substrate combinations, suggesting a decline of mitochondrial density. Oxidative phosphorylation and electron transfer system capacities were higher in ventricles compared to atria, but the impaired mitochondrial quality was identical in the four cardiac chambers of chronic heart failure patients. Coupling was preserved in heart disease and chronic heart failure, in contrast to the mitochondrial dysfunction observed after prolonged cold storage of cardiac tissue. Mitochondrial defects in the phosphorylation system, Complex I respiration and mass-specific fatty acid oxidation occurred early in the development of heart failure. Targeting these mitochondrial injuries with metabolic therapy may offer a promising approach to delay the progression of heart disease.     

Sex differences in circulating antibodies in nestling Pied Flycatchers Ficedula hypoleuca

Sex differences in immune function are relatively well studied in vertebrate animals, although the patterns are not always clear in birds. The study of immune responses in nestlings of wild bird populations may constitute an appropriate way to investigate inherent intersexual differences while controlling for environmental conditions such as parasitism that affect male and female individuals growing in the same nest. We studied whether the cell‐mediated immune response, as measured by phytohaemagglutinin (PHA) injection, and the levels of circulating antibodies differ between sexes of Pied Flycatcher nestlings Ficedula hypoleuca. No sex differences in nestling cell‐mediated immune response were found, but females showed significantly higher levels of plasma immunoglobulins than males did. Although nestling birds may not have a fully functional humoral immune defence, our study indicates that sex differences in the humoral component exist at this early stage of life. Given the importance of antibodies in the fight against parasite, bacterial and viral infections, the intrinsic sex disparity in circulating antibodies may have important implications for the life history of each sex.     

Multidimensionality and intra-individual variation in host manipulation by an acanthocephalan

Trophically-transmitted parasites frequently alter multiple aspects of their host's phenotype. Correlations between modified characteristics may suggest how different traits are mechanistically related, but these potential relationships remain unexplored. We recorded 5 traits from individual isopods infected with an acanthocephalan (Acanthocephalus lucii): hiding, activity, substrate colour preference, body (pereon) coloration, and abdominal (pleon) coloration. Infected isopods hid less and had darker abdominal coloration than uninfected isopods. However, in 3 different experiments measuring hiding behaviour (time-scales of observation: 1 h, 8 h, 8 weeks), these two modified traits were not correlated, suggesting they may arise via independent mechanisms. For the shorter experiments (1 h and 8 h), confidence in this null correlation was undermined by low experimental repeatability, i.e. individuals did not behave similarly in repeated trials of the experiment. However, in the 8-week experiment, hiding behaviour was relatively consistent within individuals, so the null correlation at this scale indicates, less equivocally, that hiding and coloration are unrelated. Furthermore, the difference between the hiding behaviour of infected and uninfected isopods varied over 8 weeks, suggesting that the effect of A. lucii infection on host behaviour changes over time. We emphasize the importance of carefully designed protocols for investigating multidimensionality in host manipulation.     

Behavior of Moose Relative to a Road Network

Abstract Roads often negatively affect terrestrial wildlife, via habitat loss or fragmentation, noise, and direct mortality. We studied moose (Alces alces) behavior relative to a road network, in an area with a history of moose-vehicle accidents, to determine when moose were crossing roadways or using areas near roads and to investigate if environmental factors were involved in this behavior. We tracked 47 adult moose with Global Positioning System collars in a study area crossed by highways and forest roads. We hypothesized that moose would avoid crossing roads but would make occasional visits to roadsides to feed on sodium-rich vegetation and avoid biting insects. Further, we expected moose avoidance to be greater for highways than forest roads. We recorded 196,710 movement segments but only observed 328 highway and 1,172 forest-road crossings (16 and 10 times lower than expected by chance). Moose usually avoided road proximity up to ≥500 m on each side but 20% of collared moose made visits to areas within 50 m of highways, which might have resulted from moose searching for sodium in vegetation and roadside salt pools. In fact, vegetation along highways had higher sodium concentrations and was browsed in similar proportions to vegetation in adjacent forest, despite moose avoidance of these zones. Moose, however, did not use areas near roads more during periods of biting insect abundance. Our results supported the hypothesis of scale-dependent selection by moose; avoidance of highways at a coarse scale may confer long-term benefits, whereas selection of highway corridors at finer scales may be part of a strategy to overcome short-term limiting factors such as sodium deficiency. We found a positive relationship between home-range size and the proportion of road axes they contained, suggesting that moose either compensated for habitat loss or made specific movements along highways to gather sodium. The presence of sodium along highways likely increases moose-vehicle accident risks. Removal of salt pools or use of a de-icing salt other than sodium chloride should render highway surroundings less attractive to moose.     

Lymphangiogenesis in post-natal tissue remodeling: lymphatic endothelial cell connection with its environment

The main physiological function of the lymphatic vasculature is to maintain tissue fluid homeostasis. Lymphangiogenesis or de novo lymphatic formation is closely associated with tissue inflammation in adults (i.e. wound healing, allograft rejection, tumor metastasis). Until recently, research on lymphangiogenesis focused mainly on growth factor/growth factor-receptor pathways governing this process. One of the lymphatic vessel features is the incomplete or absence of basement membrane. This close association of endothelial cells with the underlying interstitial matrix suggests that cell–matrix interactions play an important role in lymphangiogenesis and lymphatic functions. However, the exploration of interaction between extracellular matrix (ECM) components and lymphatic endothelial cells is in its infancy. Herein, we describe ECM–cell and cell–cell interactions on lymphatic system function and their modification occurring in pathologies including cancer metastasis.