Signaling in a polluted world: oxidative stress as an overlooked mechanism linking contaminants to animal communication

The capacity to communicate effectively with other individuals plays a critical role in the daily life of an individual and can have important fitness consequences. Animals rely on a number of visual and non-visual signals, whose production brings costs to the individual. The theory of honest signaling states that these costs are higher for low than for high-quality individuals, which prevents cheating and makes signals, such as skin and plumage colouration, indicators of individual’s quality or condition. The condition-dependent nature of signals makes them ideally suited as indicators of environmental quality, implying that signal production might be affected by contaminants. In this mini-review article, we have made the point that oxidative stress (OS) is one overlooked mechanism linking exposure to contaminants to signaling because (i) many contaminants can influence the individual’s oxidative balance, and (ii) generation of both visual and non-visual signals is sensitive to oxidative stress. To this end, we have provided the first comprehensive review on the way both non-organic (heavy metals, especially mercury) and organic (persistent organic pollutants) contaminants may influence either OS or sexual signaling. We have also paid special attention to emerging classes of pollutants like brominated flame-retardants and perfluoroalkoxy alkanes in order to stimulate research in this area. We have finally provided suggestions and warnings for future work on the links among OS, sexual signaling and contaminant exposure

Pre- and post-natal stress programming: from genes to physiology

In a variety of vertebrate species, early life environmental cues are important drivers of an individual’s phenotypic trajectories, priming physiological pathways, with consequences for growth, reproductive-related traits and lifespan. These phenotypic responses are believed to be adaptive in the short-term, but may impinge on health and survival over the long-term. Much of the work in this field has focused on the potential constraints imposed on animals after exposure to early life adversities, including nutritional deficit, sibling competition, and high predator pressure. Such stressful experiences can result in direct, but also indirect (via the maternal route) increases in the exposure to glucocorticoid stress hormones in the developing individuals. Glucocorticoids, whose production and secretion is regulated by the Hypothalamic-Pituitary-Adrenal axis (HPA axis), have been hypothesised to be the main candidates mediating the programming effects of developmental stress. Earlier predictions based on this assumption came from studies conducted in mammals. In mammals it is particularly difficult to manipulate exposure to circulating hormones in developing individuals because of the physiological intimacy between mother and offspring via the placenta and lactation. Here, I circumvent this complicating factor by using the precocial Japanese quail as a study species. In chapter 2 I measure corticosterone (B, the main avian glucocorticoid) stress responses to a standardised environmental stressor in growing quail aged 8- and 16-days-old. The results are consistent with those previously reported in other precocial birds, showing that the magnitude of the stress response (i.e. peak B within 30 min period) is higher in the 8- than the 16-day-old hatchlings. I find no differences in baseline B concentrations between the two groups. I then describe the main experiment in which I elevate B concentrations in ovo and/or in the endogenous circulation of the hatchlings (oral B administration from day 5 to day 19 post-hatching) in order to obtain four distinct phenotypes: pre-hatching B-treated birds, post-hatching B-treated birds, both pre- and post-hatching B-treated birds, and controls. I examine the specific and combined effects of pre- and post-hatching B on (1) growth trajectories and physiological stress responses before sexual maturity (post-hatch day 22) and upon adulthood (post-hatch day 64); (2) adult gene expression patterns within the hippocampus and hypothalamus, and (3) oxidative stress in the blood and the brain in the adults. The main results of Chapter 3 show that post-hatching B, regardless of pre-hatching experiences, decrease HPA axis responsiveness in the juveniles, but only in the female quail; whilst pre-hatching stress, when not combined with post-hatching B, increase HPA responsiveness in both sexes upon adulthood. I also show that both pre- and post-hatching B induce short-term alterations in triglyceride basal concentrations, which are linked with the sex and basal glucose concentrations of the birds; the effects of pre-hatching B exposure were visible also upon adulthood with sex-specific alterations on basal glucose concentrations. Overall these results suggest that early life stress can trigger both transient and permanent physiological changes, depending on the sex and the quality of both the pre- and post-hatching environment. In Chapter 4 I show that the gene expression responses to pre- and post-hatching B are overall subtle, results similar to those reported in previous genomic studies that have manipulated early life rearing environments. The effects are, however, distinguishable, strongly tissue-specific and involve well characterised key candidate genes in the regulation of the HPA axis. These data also suggest important novel regulatory mechanisms, likely linked with cellular redox state, which may be driving the long-term effects of developmental stress. Finally, in chapter 5, I show that developmental B induces alterations in the basal antioxidant defences upon adulthood. The magnitude of these effects, once more, depends upon the timing of exposure, interactions between the pre- and post-hatching B and the tissue examined. As there are no differences in terminal oxidative damage, these results suggest that the B-treated birds could avoid oxidative stress via altering body oxidative defences. In summary, my findings throughout this thesis, illustrate the complexity of glucocorticoid programming and the importance of integrating analyses at multiple levels, from physiology to genome-wide investigations. The results of this thesis also strengthen the importance of examining the effects of early life stress over differing life stages in order to consider the overall balance of costs and benefits that may ultimately affect Darwinian fitness and survival

Environmental conditions can modulate the links among oxidative stress, age, and longevity

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2′-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age–related change

Pre- and post-natal stress programming : developmental exposure to glucocorticoids causes long-term brain-region specific changes to transcriptome in the precocial Japanese quail

Funding was provided by a Kelvin Smith PhD Scholarship from the University of Glasgow (VM, PH, JR, and KAS), and Biotechnology and Biological Sciences Research Council David Phillips Research Fellowship (K.A.S.).Exposure to stress during early development can permanently influence an individual's physiology and behavior, and affect its subsequent health. The extent to which elevated glucocorticoids cause such long-term “programming” remains largely untested. Here, using the Japanese quail as our study species, we independently manipulated exposure to corticosterone during pre- and/or post-natal development and investigated the subsequent effects on global gene expression profiles within the hippocampus and hypothalamus upon adulthood. Our results showed that the changes in transcriptome profiles in response to corticosterone exposure clearly differed between the hippocampus and the hypothalamus. We also showed that these effects depended on the developmental timing of exposure and identified brain-region specific gene expression patterns that were either (1) similarly altered by corticosterone regardless of the developmental stage in which hormonal exposure occurred, or (2) specifically and uniquely altered by either pre-natal or post-natal exposure to corticosterone. Corticosterone-treated birds showed alterations in networks of genes which included known markers of the programming actions of early life adversity (e.g. brain-derived neurotrophic factor, and mineralocorticoid receptor within the hippocampus; corticotropin-releasing hormone and serotonin receptors in the hypothalamus). Altogether, these findings provide for the first time experimental support to the hypothesis that exposure to elevated glucocorticoids during development may be a key hormonal signaling pathway through which the long-term phenotypic effects associated with early life adversity emerge and potentially persist throughout the lifespan. These data also highlight that stressors might have different long-lasting impacts on the brain transcriptome depending on the developmental stage in which they are experienced; more work is now required to relate these mechanisms to organismal phenotypic differences.Publisher PDFPeer reviewe

Intergenerational effects on offspring telomere length: interactions among maternal age, stress exposure and offspring sex

Offspring produced by older parents often have reduced longevity, termed the Lansing effect. Because adults usually have similar-aged mates, it is difficult to separate effects of maternal and paternal age, and environmental circumstances are also likely to influence offspring outcomes. The mechanisms underlying the Lansing effect are poorly understood. Variation in telomere length and loss, particularly in early life, is linked to longevity in many vertebrates, and therefore changes in offspring telomere dynamics could be very important in this context. We examined the effect of maternal age and environment on offspring telomere length in zebra finches. We kept mothers under either control (ad libitum food) or more challenging (unpredictable food) circumstances and experimentally minimized paternal age and mate choice effects. Irrespective of the maternal environment, there was a substantial negative effect of maternal age on offspring telomere length, evident in longitudinal and cross-sectional comparisons (average of 39% shorter). Furthermore, in young mothers, sons reared by challenged mothers had significantly shorter telomere lengths than sons reared by control mothers. This effect disappeared when the mothers were old, and was absent in daughters. These findings highlight the importance of telomere dynamics as inter-generational mediators of the evolutionary processes determining optimal age-specific reproductive effort and sex allocation

Bio-Inspired Dielectric Resonator Antenna for Wideband Sub-6 GHz Range

Through the years, inspiration from nature has taken the lead for technological development and improvement. This concept firmly applies to the design of the antennas, whose performances receive a relevant boost due to the implementation of bio-inspired geometries. In particular, this idea holds in the present scenario, where antennas working in the higher frequency range (5G and mm-wave), require wide bandwidth and high gain; nonetheless, ease of fabrication and rapid production still have their importance. To this aim, polymer-based 3D antennas, such as Dielectric Resonator Antennas (DRAs) have been considered as suitable for fulfilling antenna performance and fabrication requirements. Differently from numerous works related to planar-metal-based antenna development, bio-inspired DRAs for 5G and mm-wave applications are at their beginning. In this scenario, the present paper proposes the analysis and optimization of a bio-inspired Spiral shell DRA (SsDRA) implemented by means of Gielis' superformula, with the goal of boosting the antenna bandwidth. The optimized SsDRA geometrical parameters were also determined and discussed based on its fabrication feasibility exploiting Additive Manufacturing technologies. The results proved that the SsDRA provides relevant bandwidth, about 2 GHz wide, and satisfactory gain (3.7 dBi and 5 dBi, respectively) at two different frequencies, 3.5 GHz and 5.5 GHz

Surface displaced alfa-enolase of Lactobacillus plantarum is a fibronectin binding protein

Background: Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals. Results: We show the identification of a Lactobacillus plantarum LM3 cell surface protein (48 kDa), which specifically binds to human fibronectin (Fn), an extracellular matrix protein. By means of mass spectrometric analysis this protein was identified as the product of the L. plantarum enoA1 gene, coding the EnoA1 alfa-enolase. Surface localization of EnoA1 was proved by immune electron microscopy. In the mutant strain LM3-CC1, carrying the enoA1 null mutation, the 48 kDa adhesin was not anymore detectable neither by anti-enolase Western blot nor by Fn-overlay immunoblotting assay. Moreover, by an adhesion assay we show that LM3-CC1 cells bind to fibronectin-coated surfaces less efficiently than wild type cells, thus demonstrating the significance of the surface displaced EnoA1 protein for the L. plantarum LM3 adhesion to fibronectin. Conclusion: Adhesion to host tissues represents a crucial early step in the colonization process of either pathogens or commensal bacteria. We demonstrated the involvement of the L. plantarum Eno A1 alfa-enolase in Fn-binding, by studying LM3 and LM3-CC1 surface proteins. Isolation of LM3-CC1 strain was possible for the presence of expressed enoA2 gene in the L. plantarum genome, giving the possibility, for the first time to our knowledge, to quantitatively compare adhesion of wild type and mutant strain, and to assess doubtless the role of L. plantarum Eno A1 as a fibronectin binding protein. © 2009 Castaldo et al; licensee BioMed Central Ltd

Nuclear role for human Argonaute-1 as an estrogen-dependent transcription coactivator

In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers.Moreover, we show that AGO1 interacts with ERα and that this interaction is also increased by E2 treatment, but occurs in the absence of RNA. We show that AGO1 acts positively as a coactivator in estradiol-triggered transcription regulation by promoting ERα binding to its enhancers. Consistently, AGO1 depletion decreases long-range contacts between ERα enhancers and their target promoters. Our results point to a role of AGO1 in transcriptional regulation in human cells that is independent from small RNA binding.Fil: Gómez Acuña, Luciana Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Nazer, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Rodríguez Seguí, Santiago Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Pozzi, María Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Buggiano, Valeria Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Marasco, Luciano Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Agirre, Eneritz. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: He, Cody. University of Chicago; Estados UnidosFil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person