The effect of maternal immunization on female oxidative status, yolk antioxidants and offspring survival in a songbird.

Immune defense involves inflammatory reactions in which immune cells produce reactive oxygen species (ROS) to fight pathogens. ROS may however cause damage to the host if they are not balanced by antioxidant defenses. Therefore, one should expect individuals undergoing an immune reaction to use antioxidants to prevent oxidative stress. Antioxidants are vital compounds that provide important protection against oxidative damage of embryos and newly hatched chicks. Thus, during egg laying a female that contracted an infection may face a trade-off between the allocation of antioxidants into self-maintenance and into her offspring via the eggs. In our study we investigated whether immunized females face this trade-off and consequently modify the antioxidant allocation into the eggs and whether this allocation affects offspring performance. We injected female zebra finches (Taeniopygia guttata) with lipopolysaccharide prior to egg laying while some females were left unimmunized. We removed the second egg of each clutch, while we allowed the other eggs to hatch. We assessed oxidative stress in females 24h after immunization, yolk antioxidant capacity of the second egg of the clutch and survival success of the offspring until adulthood. Compared to controls, immunized females had higher oxidative damage, but similar plasma non-enzymatic antioxidant levels. The treatment did not affect yolk antioxidants, clutch size, laying date and offspring survival. However, we found a positive correlation between yolk antioxidant capacity and offspring survival, irrespective of the treatment. Our study suggests that our immune challenge may not have changed female strategy of antioxidant allocation between self-maintenance and offspring survival.

Experimentally increased reproductive effort alters telomere length in the blue tit (Cyanistes caeruleus).

Telomeres have recently been suggested to play important role in ageing and are considered to be a reliable ageing biomarkers. The life history theory predicts that costs of reproduction should be expressed in terms of accelerated senescence, and some empirical studies do confirm such presumption. Thus, a link between reproductive effort and telomere dynamics should be anticipated. Recent studies have indeed demonstrated that reproduction may trigger telomere loss, but actual impact of reproductive effort has not received adequate attention in experimental studies. Here, we experimentally manipulated reproductive effort by increasing the brood size in the wild blue tit (Cyanistes caeruleus). We show that parents attending enlarged broods experienced larger yearly telomere decay in comparison to control birds attending unaltered broods. In addition, we demonstrate that the change in telomere length differs between sexes, but this effect was independent from our treatment. To our knowledge, this is the first experimental study in the wild revealing that telomere dynamics may be linked to reproductive effort. Thus, telomere shortening may constitute one of the potential proximate mechanisms mediating the costs of reproduction.

The receptor tyrosine kinase Axl regulates cell-cell adhesion and stemness in cutaneous squamous cell carcinoma.

Axl is a receptor tyrosine kinase (RTK) upregulated in various tumors including cutaneous squamous cell carcinoma (SCC). Axl expression correlates with poor prognosis and induction of epithelial-mesenchymal transition (EMT), hence we hypothesized that Axl is involved in the disruption of cell-cell adhesion to allow invasion and chemotherapy resistance of the cancer stem cell population. Cutaneous SCC cell lines with stable knockdown of Axl were generated using retroviral vectors. Axl depletion altered expression of intercellular junction molecules increasing cell-cell adhesion with downregulation of Wnt and TGFßR signaling. Furthermore, Axl expression correlated with the expression of putative cancer stem cell markers, CD44 and ALDH1, increased resistance to chemotherapy drugs, enhanced sphere formation ability and expression of EMT features by cancer stem cells. Axl depletion resulted in loss of tumor formation in an in vivo zebrafish xenograft model. In conclusion, these data suggest that abrogation of Axl results in loss of cancer stem cell properties indicating a role for Axl as a therapeutic target in chemotherapy-resistant cancer.

Determinants of distribution and prevalence of avian malaria in blue tit populations across Europe: separating host and parasite effects.

Although avian malarial parasites are globally distributed, the factors that affect the geographical distribution and local prevalence of different parasite lineages across host populations or species are still poorly understood. Based on the intense screening of avian malarial parasites in nine European blue tit populations, we studied whether distribution ranges as well as local adaptation, host specialization and phylogenetic relationships can determine the observed prevalences within populations. We found that prevalence differed consistently between parasite lineages and host populations, indicating that the transmission success of parasites is lineage specific but is partly shaped by locality-specific effects. We also found that the lineage-specific estimate of prevalence was related to the distribution range of parasites: lineages found in more host populations were generally more prevalent within these populations. Additionally, parasites with high prevalence that were also widely distributed among blue tit populations were also found to infect more host species. These findings suggest that parasites reaching high local prevalence can also realize wide distribution at a global scale that can have further consequences for host specialization. Although phylogenetic relationships among parasites did not predict prevalence, we detected a close match between a tree based on the geographic distance of the host populations and the parasite phylogenetic tree, implying that neighbouring host populations shared a related parasite fauna.

Sex-specific heritability of cell-mediated immune response in the blue tit nestlings (Cyanistes caeruleus).

Here, we aimed at estimating sex-specific heritabilities of cell-mediated immune response (CMI) in the blue tit nestlings (Cyanistes caeruleus). To separate genetic and environmental components of the phenotypic variance in CMI (measured using phytohaemagglutinin assay), we performed a cross-fostering experiment. Additionally, controlled environmental variation was introduced by enlarging some broods. Our analyses revealed a significant genetic component (as approximated by the nest-of-origin term) of the phenotypic variance in immune response. More importantly, these genetic effects differed between sexes and experimentally manipulated brood sizes, as indicated by significant genotype-by-sex and genotype-by-environment interactions. We discuss possible causes of such sexual dimorphism in gene expression and suggest that sex- and environment-specific genetic interactions may contribute to the maintenance of genetic variability in traits related to immune functions.

Genetic and environmental variation in immune response of collared flycatcher nestlings.

This paper aims at partitioning genetic and environmental contribution to the phenotypic variance in nestling immune function measured with the hypersensitivity test after inoculation with phytohaemagglutinin. A cross-fostering experiment with artificial enlargement of some broods was conducted. Variation in nestling immune response was related to their common origin, which suggests heritable component of cell-mediated immunity. A common rearing environment also explained a significant part of variation. However, deterioration of rearing conditions as simulated by enlargement of brood size did not affect nestling immunocompetence, although it affected nestling body mass. Variation in body mass explained some of the variation in immune response related to rearing environment, which means that growth is more sensitive to the shifts in rearing conditions than the development of immune function. Heritable variation in immune response suggests that there should be potential for selection to operate and the micro evolutionary changes in immunity of flycatcher nestlings are possible.

Cell-mediated immunity predicts the probability of local recruitment in nestling blue tits.

We investigated whether the variation in T-cell-mediated immune function of blue tit nestlings affected their fledgling success and the probability of local survival. We studied the relationship between immune function and survival under two rearing conditions: control, unmanipulated, and experimentally enlarged broods. Brood enlargement had negative effects on nestling immune response. Immune response was positively related to fledgling success and it predicted the probability of local recruitment. However, the relationship between immune response and the probability of recruitment was significantly positive only among control broods and nonsignificant among enlarged broods. The effect of immune response on the recruitment probability was not affected by variation in body mass. Our study suggests that selection for immune responsiveness seems to be weak or even absent under unfavourable rearing conditions as simulated by brood size enlargement. Therefore, year-to-year environmental variation and environmental heterogeneity may constrain evolution towards higher immune responsiveness.

Age-related decline in humoral immune function in Collared Flycatchers.

Although immune function usually declines with age in humans and captive animals, little is known about whether immune function deteriorates with age in natural populations. Here we present evidence for such an age-related deterioration in humoral immune function from a wild population of the Collared Flycatcher (Ficedula albicollis). In this study, young (1-year old), mid-age (3-year old) and old (5-6-year old) females were challenged with a nonpathogenic antigen, sheep red blood cells (SRBC), while provisioning their nestlings. The level of antibodies against SRBC was measured thereafter. Old females showed markedly lower humoral immune response and produced fledglings of lower body mass in comparison with the other two age classes. Moreover, the age classes differed in the relationship between immune response and fledgling body mass with mid-age females showing a significant positive relationship while the relationship was negative but nonsignificant among young and old females. The results are discussed in light of existing theories of optimal resource allocation, ageing and the theory of terminal investment.

The mechanism of action of DNA photolyases.

Structural analysis, biochemistry and model studies have provided new insights into the mechanism of action of photolyases. The light-driven electron and energy transfer events that lead to the photolyase-catalyzed repair of lethal, mutagenic and carcinogenic UV-light-induced DNA lesions have all been examined in the past few years.

Hormonal decline in elderly men and male menopause.

Much has been written about female menopause, but hormonal decline in men indicative of a similar menopause is a relatively new concept. Hormonal decline in men is a gradual and often occult process. Many men do not experience noticeable symptoms, but those who do usually experience a decline in sexual desire and ability that may be attributed to aging. Some men may hide these symptoms. Hormonal replacements and herbal therapies may be helpful. Nurses must conduct careful histories and physical examinations to elicit disclosure of symptoms of hormonal decline in this population.

Diversity of age-specific reproductive rates may result from ageing and optimal resource allocation.

This paper reports the results of a dynamic programming model which optimizes resource allocation to growth, reproduction and repair of somatic damage, based on the disposable soma theory of ageing. Here it is shown that different age-dependent patterns of reproductive rates are products of optimal lifetime strategies of resource partitioning. The array of different reproductive patterns generated by the model includes those in which reproduction begins at the maximum rate at maturity and then declines to the end of life, or increases up to a certain age and then drops. The observed patterns reflect optimal resource allocation shaped by the level of extrinsic mortality. A continuous decline in the reproductive rate from the start of reproduction is associated with high extrinsic mortality, and an early increase in the reproductive rate occurs under low extrinsic mortality. A long-lived organism shows a low reproductive rate early in life, and short-lived organisms start reproduction at the maximum rate.

Costs of incubation and immunocompetence in the collared flycatcher.

This paper investigates the costs of incubation in terms of reduced reproductive success and investigates whether incubation competes with immune function for resources. I performed a clutch size manipulation experiment in which two eggs were either removed from or added to the nests of collared flycatchers, Ficedula albicollis, for 1 week during incubation and subsequently returned to their original nests before hatching. To induce immune response, the females were challenged with sheep red blood cells. While the duration of incubation, hatching success and fledgling number did not differ between experimental groups, fledgling condition was significantly lower in broods that had been enlarged during incubation. Neither the females' condition nor their ability to respond to a novel antigen differed between treatments. The relationship between antibody production and female condition was significantly positive, but only among females incubating reduced clutches. I conclude that the costs of incubation in the collared flycatcher are not negligible and are manifested only at the chick-rearing phase.

Between Beveridge and Bismarck--options for health care financing in central and eastern Europe.

A government-run national health service (the Beveridge model) can provide care for all at a reasonable cost but cannot avoid the dangers of poor quality. An insurance-based system (the Bismarck model) can achieve high quality but cannot ensure care for all at an affordable cost. The best chance of achieving a reliable financial base for health services is to use a combination of both these approaches.

Primary amoebic meningoencephalitis: a report of two cases and antibiotic and immunologic studies.

In the summer of 1978, two children who had recently been swimming in freshwater lakes in Florida died from primary amoebic meningoencephalitis. Despite early and intensive treatment with amphotericin B, both patients died three to five days after the onset of illness. Amoebae were observed in wet preparations of cerebrospinal fluid and in sections of cerebral tissue and were identified as Naegleria fowleri by the indirect immunofluorescent antibody technique. The amoebae were highly virulent in mice. The isolate of N. fowleri was extremely sensitive in vitro to amphotericin B (minimal inhibitory concentration [MIC], 0.15 microgram/ml), somewhat sensitive to miconazole (MIC, 25 micrograms/ml), and resistant to rifampin (MIC, less than or equal to 100 micrograms/ml). Treatment with amphotericin B (7.5 mg/kg of body weight per day) administered intraperitoneally protected 60% of the mice. Lower doses of amphotericin B alone or in combination with miconazole (100 mg/kg) or rifampin (220 mg/kg) were not protective. These results suggest that amphotericin B remains the single effective agent in treatment of primary amoebic meningoencephalitis.

Nosocomial Klebsiella infections in an intensive care nursery.

Nosocomial infections in an intensive care nursery (ICN) due to kanamycin-resistant Klebsiella pneumoniae during a four-month period with an infection rate of 12% and mortality of 47% are reported. Emergence of this organism was thought to be due to the widespread use of kanamycin. Transmission probably occurred via hands of personnel contaminated during care of colonized or infected infants. Control measures advocated are better handwashing technic and discriminate use of antibiotics. This report emphasizes the need for awareness of this continuous threat and for infection surveillance in an ICN.