931 resultados para EARLY ADAPTIVE RESPONSES


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Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease.

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CD4+ T cells play a crucial in the adaptive immune system. They function as the central hub to orchestrate the rest of immunity: CD4+ T cells are essential governing machinery in antibacterial and antiviral responses by facilitating B cell affinity maturation and coordinating the innate and adaptive immune systems to boost the overall immune outcome; on the contrary, hyperactivation of the inflammatory lineages of CD4+ T cells, as well as the impairments of suppressive CD4+ regulatory T cells, are the etiology of various autoimmunity and inflammatory diseases. The broad role of CD4+ T cells in both physiological and pathological contexts prompted me to explore the modulation of CD4+ T cells on the molecular level.

microRNAs (miRNAs) are small RNA molecules capable of regulating gene expression post-transcriptionally. miRNAs have been shown to exert substantial regulatory effects on CD4+ T cell activation, differentiation and helper function. Specifically, my lab has previously established the function of the miR-17-92 cluster in Th1 differentiation and anti-tumor responses. Here, I further analyzed the role of this miRNA cluster in Th17 differentiation, specifically, in the context of autoimmune diseases. Using both gain- and loss-of-function approaches, I demonstrated that miRNAs in miR-17-92, specifically, miR-17 and miR-19b in this cluster, is a crucial promoter of Th17 differentiation. Consequently, loss of miR-17-92 expression in T cells mitigated the progression of experimental autoimmune encephalomyelitis and T cell-induced colitis. In combination with my previous data, the molecular dissection of this cluster establishes that miR-19b and miR-17 play a comprehensive role in promoting multiple aspects of inflammatory T cell responses, which underscore them as potential targets for oligonucleotide-based therapy in treating autoimmune diseases.

To systematically study miRNA regulation in effector CD4+ T cells, I devised a large-scale miRNAome profiling to track in vivo miRNA changes in antigen-specific CD4+ T cells activated by Listeria challenge. From this screening, I identified that miR-23a expression tightly correlates with CD4+ effector expansion. Ectopic expression and genetic deletion strategies validated that miR-23a was required for antigen-stimulated effector CD4+ T cell survival in vitro and in vivo. I further determined that miR-23a targets Ppif, a gatekeeper of mitochondrial reactive oxygen species (ROS) release that protects CD4+ T cells from necrosis. Necrosis is a type of cell death that provokes inflammation, and it is prominently triggered by ROS release and its consequent oxidative stress. My finding that miR-23a curbs ROS-mediated necrosis highlights the essential role of this miRNA in maintaining immune homeostasis.

A key feature of miRNAs is their ability to modulate different biological aspects in different cell populations. Previously, my lab found that miR-23a potently suppresses CD8+ T cell cytotoxicity by restricting BLIMP1 expression. Since BLIMP1 has been found to inhibit T follicular helper (Tfh) differentiation by antagonizing the master transcription factor BCL6, I investigated whether miR-23a is also involved in Tfh differentiation. However, I found that miR-23a does not target BLIMP1 in CD4+ T cells and loss of miR-23a even fostered Tfh differentiation. This data indicate that miR-23a may target other pathways in CD4+ T cells regarding the Tfh differentiation pathway.

Although the lineage identity and regulatory networks for Tfh cells have been defined, the differentiation path of Tfh cells remains elusive. Two models have been proposed to explain the differentiation process of Tfh cells: in the parallel differentiation model, the Tfh lineage is segregated from other effector lineages at the early stage of antigen activation; alternatively, the sequential differentiation model suggests that naïve CD4+ T cells first differentiate into various effector lineages, then further program into Tfh cells. To address this question, I developed a novel in vitro co-culture system that employed antigen-specific CD4+ T cells, naïve B cells presenting cognate T cell antigen and BAFF-producing feeder cells to mimic germinal center. Using this system, I were able to robustly generate GC-like B cells. Notably, well-differentiated Th1 or Th2 effector cells also quickly acquired Tfh phenotype and function during in vitro co-culture, which suggested a sequential differentiation path for Tfh cells. To examine this path in vivo, under conditions of classical Th1- or Th2-type immunizations, I employed a TCRβ repertoire sequencing technique to track the clonotype origin of Tfh cells. Under both Th1- and Th2- immunization conditions, I observed profound repertoire overlaps between the Teff and Tfh populations, which strongly supports the proposed sequential differentiation model. Therefore, my studies establish a new platform to conveniently study Tfh-GC B cell interactions and provide insights into Tfh differentiation processes.

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During summer 2014 (mid-July - mid-September 2014), early life-stage Fucus vesiculosus were exposed to combined ocean acidification and warming (OAW) in the presence and absence of enhanced nutrient levels (OAW x N experiment). Subsequently, F. vesiculosus germlings were exposed to a final upwelling disturbance during 3 days (mid-September 2014). Experiments were performed in the near-natural scenario "Kiel Outdoor Benthocosms" including natural fluctuations in the southwestern Baltic Sea, Kiel Fjord, Germany (54°27 'N, 10°11 'W). Genetically different sibling groups and different levels of genetic diversity were employed to test to which extent genetic variation would result in response variation. The data presented here show the phenotypical response (growth and survival) of the different experimental populations of F. vesiculosus under OAW, nutrient enrichment and the upwelling event. Log effect ratios demonstrate the responses to enhanced OAW and nutrient concentrations relative to the ambient conditons. Carbon, nitrogen content (% DW) and C:N ratios were measured after the exposure of ambient and high nutrient levels. Abiotic conditions the OAW x nutrient experiment and the upwelling event, are shown.

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Climate change is expected to have wide-ranging impacts on urban areas and creates additional challenges for sustainable development. Urban areas are inextricably linked with climate change, as they are major contributors to it, while also being particularly vulnerable to its impacts. Climate change presents a new challenge to urban areas, not only because of the expected rises in temperature and sea-level, but also the current context of failure to fully address the institutional barriers preventing action to prepare for climate change, or feedbacks between urban systems and agents. Despite the importance of climate change, there are few cities in developing countries that are attempting to address these issues systematically as part of their governance and planning processes. While there is a growing literature on the risks and vulnerabilities related to climate change, as yet there is limited research on the development of institutional responses, the dissemination of relevant knowledge and evaluation of tools for practical planning responses by decision makers at the city level. This thesis questions the dominant assumptions about the capacity of institutions and potential of adaptive planning. It argues that achieving a balance between climate change impacts and local government decision-making capacity is a vital for successful adaptation to the impacts of climate change. Urban spatial planning and wider environmental planning not only play a major role in reducing/mitigating risks but also have a key role in adapting to uncertainty in over future risk. The research focuses on a single province - the biggest city in Vietnam - Ho Chi Minh City - as the principal case study to explore this argument, by examining the linkages between urban planning systems, the structures of governance, and climate change adaptation planning. In conclusion it proposes a specific framework to offer insights into some of the more practical considerations, and the approach emphasises the importance of vertical and horizontal coordination in governance and urban planning.

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Los indicadores de sostenibilidad climática constituyen herramientas fundamentales para complementar las políticas de ordenamiento del territorio urbano y pueden beneficiar la calidad de vida sus habitantes. En el presente trabajo se diseñó un indicador climático urbano para la ciudad de Bahía Blanca considerando variables meteorológicas y análisis de la percepción social. El mismo permitió delimitar la ciudad en cuatro regiones bien diferenciadas entre sí. A partir de entonces, se realizó una propuesta sostenible para mitigar los efectos adversos del clima a partir de la aplicación del método DPSIR. Las mismas estuvieron destinadas a mejorar las condiciones de vida de la población. Los resultados permitieron considerar que una pronta implementación de la misma junto con una activa participación de los actores sociales y los tomadores de decisiones es necesaria para mejorar las condiciones actuales en la que se encuentra la ciudad. Con las medidas propuestas, la población local sabrá cómo actuar ante la ocurrencia de distintos eventos extremos, eventos de desconfort climático, etc. Al ser un método sencillo, la metodología aplicada en este estudio puede replicarse en otras ciudades del mundo con el objetivo de mejorar la calidad de vida de los habitantes.

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During the epoch when the first collapsed structures formed (6<z<50) our Universe went through an extended period of changes. Some of the radiation from the first stars and accreting black holes in those structures escaped and changed the state of the Intergalactic Medium (IGM). The era of this global phase change in which the state of the IGM was transformed from cold and neutral to warm and ionized, is called the Epoch of Reionization.In this thesis we focus on numerical methods to calculate the effects of this escaping radiation. We start by considering the performance of the cosmological radiative transfer code C2-Ray. We find that although this code efficiently and accurately solves for the changes in the ionized fractions, it can yield inaccurate results for the temperature changes. We introduce two new elements to improve the code. The first element, an adaptive time step algorithm, quickly determines an optimal time step by only considering the computational cells relevant for this determination. The second element, asynchronous evolution, allows different cells to evolve with different time steps. An important constituent of methods to calculate the effects of ionizing radiation is the transport of photons through the computational domain or ``ray-tracing''. We devise a novel ray tracing method called PYRAMID which uses a new geometry - the pyramidal geometry. This geometry shares properties with both the standard Cartesian and spherical geometries. This makes it on the one hand easy to use in conjunction with a Cartesian grid and on the other hand ideally suited to trace radiation from a radially emitting source. A time-dependent photoionization calculation not only requires tracing the path of photons but also solving the coupled set of photoionization and thermal equations. Several different solvers for these equations are in use in cosmological radiative transfer codes. We conduct a detailed and quantitative comparison of four different standard solvers in which we evaluate how their accuracy depends on the choice of the time step. This comparison shows that their performance can be characterized by two simple parameters and that the C2-Ray generally performs best.

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Thesis (Ph.D.)--University of Washington, 2016-08

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During the last years tropical forest has been a target of intense study especially due to its recent big scale destruction. Although a lot still needs to be explored, we start realizing how negative can the impact of our actions be for the ecosystem. Subsequently, the living community have been developing strategies to overcome this problem avoiding bottlenecks or even extinctions. Cooperative breeding (CB) has been recently pointed out as one of those strategies. CB is a breeding system where more than two individuals raise one brood. In most of the cases, extra individuals are offspring that delay their dispersal and independent breeding what allows them to help their parents raising their siblings in the subsequent breeding season. Such behavior is believed to be due, per example, to the lack of mates or breeding territories (ecological constraints hypothesis), a consequence of habitat fragmentation and/or disturbance. From this point, CB is easily promoted by a higher reproductive success of group vs pairs or single individuals. Accordingly, during this thesis I explore the early post-fledging survival of a cooperative breeding passerine, namely the impact of individual/habitat quality in its survival probability during the dependence period of the chicks. Our study species is the Cabanis’s greenbul (Phyllastrephus cabanisi), a medium-sized, brownish passerine, classified within the Pycnonotidae family. It is found over part of Central Africa in countries such as Angola, Democratic Republic of the Congo, Mozambique and Kenya, inhabiting primary and secondary forests, as well as woodland of various types up to 2700m of altitude. Previous studies have concluded that PC is a facultative cooperative breeder. This study was conducted in Taita Hills (TH) at the Eastern Arc Mountains (EAM), a chain of mountains running from Southeast Kenya to the South of Tanzania. TH comprises an area of 430 ha and has been suffering intense deforestation reflecting 98% forest reduction over the last 200 years. Nowadays its forest is divided in fragments and our study was based in 5of those fragments. We access the post-fledging survival through radio-telemetry. The juvenile survey was done through the breeding females in which transmitters were placed with a leg-loop technique. Ptilochronology is consider to be the study of feather growth bars and has been used to study the nutritional state of a bird. This technique considers that the feather growth rate is positively proportional to the individual capability of ingesting food and to the food availability. This technique is therefore used to infer for individual/habitat quality. Survival was lowest during the first 5 days post-fledging representing 53.3%. During the next 15 days, risk of predation decreased with only 14.3% more deceased individuals. This represents a total of only 33% survived individuals in the end of the 50 days. Our results showed yet a significant positive relationship between flock size and post-fledging survival as well as between ptilochronology values and post-fledgling survival. In practice, these imply that on this population, as bigger the flock, as greater the post fledging survival and that good habitat quality or good BF quality, will lead to a higher juvenile survival rate. We believe that CB is therefore an adaptive behaviour to the lack of mates/breeding territory originated from the mass forest destruction and disturbance. Such results confirms the critical importance of habitat quality in the post-fledging survival and, for the first time, demonstrates how flock size influences the living probability of the juveniles and therefore how it impacts the (local) population dynamics of this species. In my opinion, future research should be focus in disentangle individual and habitat quality from each other and verify which relationship exist between them. Such study will allow us to understand which factor has a stronger influence in the post-fledging survival and therefore redirect our studies in that direction. In order to confirm the negative impact of human disturbance and forest fragmentation, it would be of major relevance to compare the reproductive strategies and reproductive success of populations living in intact forests and disturbed patches.

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The auxin receptor ABP1 directly regulates plasma membrane activities including the number of PIN-formed (PIN) proteins and auxin efflux transport. Red light (R) mediated by phytochromes regulates the steady-state level of ABP1 and auxin-inducible growth capacity in etiolated tissues but, until now, there has been no genetic proof that ABP1 and phytochrome regulation of elongation share a common mechanism for organ elongation. In far red (FR)-enriched light, hypocotyl lengths were larger in the abp1-5 and abp1/ABP1 mutants, but not in tir1-1, a null mutant of the TRANSPORT-INHIBITOR-RESPONSE1 auxin receptor. The polar auxin transport inhibitor naphthylphthalamic acid (NPA) decreased elongation in the low R: FR light-enriched white light (WL) condition more strongly than in the high red: FR light-enriched condition WL suggesting that auxin transport is an important condition for FR-induced elongation. The addition of NPA to hypocotyls grown in R-and FR-enriched light inhibited hypocotyl gravitropism to a greater extent in both abp1 mutants and in phyB-9 and phyA-211 than the wild-type hypocotyl, arguing for decreased phytochrome action in conjunction with auxin transport in abp1 mutants. Transcription of FR-enriched light-induced genes, including several genes regulated by auxin and shade, was reduced 3-5-fold in abp1-5 compared with Col and was very low in abp1/ABP1. In the phyB-9 mutant the expression of these reporter genes was 5-15-fold lower than in Col. In tir1-1 and the phyA-211 mutants shade-induced gene expression was greatly attenuated. Thus, ABP1 directly or indirectly participates in auxin and light signalling.

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Milk contains numerous bioactive substances including immunoglobulins, cytokines, growth factors and components that exert antibiotic and prebiotic activity (Field, 2005). Little is known about the biological effects of individual milk bioactives, despite the fact that natural milk improves intestinal development and immune system functions in neonates (Donovan et al., 1994; Field, 2005) relative to milk formula. Characterization of the biological effects of such components is important for optimal production of infant milk formulas to be used when mother’s milk is not available. Milk components with preliminary evidence of positive effects on the intestinal growth and mucosal immunity include osteopontin (OPN). Osteopontin is a phosphorylated acidic glycoprotein expressed by a number of different immune and non-immune cells and tissues (Sodek et al., 2000). It is also present in body fluids including blood, bile and milk (Sodek et al., 2000). Osteopontin is a multifunctional protein that is implicated in a wide number of biological processes including cell survival, bone remodeling, and immune modulatory functions (Sodek et al., 2000). Furthermore, Schack and colleagues (2009) demonstrated that the concentration of OPN in human milk is considerably higher than in bovine milk and infant formulas. Taken together, it is likely that OPN plays a role in the early development of gastrointestinal tract and mucosal immune responses in infants. Since the neonatal pig shares anatomical, physiological, immunological, and metabolic similarities with the human infants (Moughan, et al., 1992), they were selected as the animal model in our studies. Our first aim was to investigate the effects of OPN on piglet intestinal development. Newborn, colostrum-deprived piglets (n=27) were randomized to receive three treatments: formula with bovine OPN (OPN; 140 mg/L); formula alone (FF); or sow reared (SR) for 21 days. Body weight, intestinal weight and length, mucosal protein and DNA content, disaccharidase activity, villus morphology, and crypt cell proliferation were measured. Statistical significance was assigned at P<0.05. No significant effects of OPN were observed for body weight, intestinal weight and length. Mucosal protein content of SR piglets was lower than FF and OPN piglets in the duodenum, but higher than FF and OPN piglets in the ileum. No significant effects of diet in mucosal DNA content were detected for the three regions of the small intestine. Lactase and sucrase activities of SR piglets were higher than the two formula-fed groups in the duodenum, lower in the ileum. No significant effects of diet on lactase and sucrase activities were noted between two formula-fed groups in the duodenum and ileum. Jejunal lactase activity of FF piglets was higher than SR piglets, whereas no significant effect of diet was observed in jejunal sucrase activity among the three groups. Duodenal and ileal villus height and villus area of SR piglets were lower than two formula-fed groups, while OPN piglets did not differ from FF piglets. There was a significant effect of diet (P<0.0001) on jejunal crypt cell proliferation, with proliferation in OPN piglets being intermediate between that of FF and SR. In summary, supplemental OPN increased jejunal crypt cell proliferation, independent of evident morphological growth, and had a minor impact on disaccharidase activity in the small intestine of neonatal piglets. Rotavirus (RV) is the most common viral cause of severe gastroenteritis in infants and young children worldwide (Parashar et al., 2006). Maeno et al. (2009) reported that OPN knockout (OPN-KO) suckling mice were more susceptible to RV infection compared to wild-type (WT) suckling mice. To detect the role of OPN in intestinal immune responses of neonates, the goal of the second study was to evaluate whether supplemental OPN influenced the serum antibody responses to RV vaccination in neonatal piglets. Newborn, colostrum-deprived piglets were randomized into two dietary groups: formula with bovine OPN (OPN; 140 mg/L) and formula alone (FF) for 35 days. On d7, piglets in each dietary group were further randomized to receive rotavirus (RV) vaccination (Rotarix®) (FF+RV and OPN+RV) or remained non-vaccinated (FF+NV and OPN+NV). Booster vaccination was provided on d14. Blood samples were collected on d7, 14, 21, 28 and 35. RV-specific serum immunoglobulin (Ig) G, IgA, IgM and total serum IgG, IgA, IgM were measured by ELISA. Statistical significance was assigned at P<0.05, with trends reported as P<0.10. Body weight gain was unaffected by diet and/or vaccination. No significant effect of oral OPN supplementation was observed for RV-specific antibody responses and total Igs levels. After the combination of dietary groups, RV piglets had significantly higher RV-specific IgM concentrations compared to NV piglets. Although there were higher means of RV-specific IgG and RV-specific IgA concentrations in RV group than their counterparts in NV group, the difference did not reach statistical significance. RV-specific IgM reached a peak at d7 post booster vaccination (PBV), whereas the RV-specific IgG and IgA peaked later at PBV 14 or 21. Total Igs were unaffected by RV vaccination but were significantly increased over time, following similar pattern as RV-specific Igs. In summary, neonatal piglets generated weak antibody responses to RV vaccination. Supplemental OPN did not enhance RV-specific serum antibody responses and total serum Igs levels in neonatal piglets with or without RV vaccination. In conclusion, we observed normal developmental changes in the small intestine and serum Igs levels in neonatal piglets over time. Oral OPN supplementation showed minimal impacts on intestinal development and no effect on serum Igs levels. The role of supplemental OPN on the growth and development of infants is still inconclusive. Future studies should measure other physiological and immunological parameters by using different models of vaccination or infection.

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Recent research on affective processing has suggested that low spatial frequency information of fearful faces provide rapid emotional cues to the amygdala, whereas high spatial frequencies convey fine-grained information to the fusiform gyrus, regardless of emotional expression. In the present experiment, we examined the effects of low (LSF, <15 cycles/image width) and high spatial frequency filtering (HSF, >25 cycles/image width) on brain processing of complex pictures depicting pleasant, unpleasant, and neutral scenes. Event-related potentials (ERP), percentage of recognized stimuli and response times were recorded in 19 healthy volunteers. Behavioral results indicated faster reaction times in response to unpleasant LSF than to unpleasant HSF pictures. Unpleasant LSF pictures and pleasant unfiltered pictures also elicited significant enhancements of P1 amplitudes at occipital electrodes as compared to neutral LSF and unfiltered pictures, respectively; whereas no significant effects of affective modulation were found for HSF pictures. Moreover, mean ERP amplitudes in the time between 200 and 500ms post-stimulus were significantly greater for affective (pleasant and unpleasant) than for neutral unfiltered pictures; whereas no significant affective modulation was found for HSF or LSF pictures at those latencies. The fact that affective LSF pictures elicited an enhancement of brain responses at early, but not at later latencies, suggests the existence of a rapid and preattentive neural mechanism for the processing of motivationally relevant stimuli, which could be driven by LSF cues. Our findings confirm thus previous results showing differences on brain processing of affective LSF and HSF faces, and extend these results to more complex and social affective pictures.

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NlmCategory="UNASSIGNED">We previously reported that TLR4(-/-) mice are refractory to mouse-adapted A/PR/8/34 (PR8) influenza-induced lethality and that therapeutic administration of the TLR4 antagonist Eritoran blocked PR8-induced lethality and acute lung injury (ALI) when given starting 2 days post infection. Herein we extend these findings: anti-TLR4- or -TLR2-specific IgG therapy also conferred significant protection of wild-type (WT) mice from lethal PR8 infection. If treatment is initiated 3 h before PR8 infection and continued daily for 4 days, Eritoran failed to protect WT and TLR4(-/-) mice, implying that Eritoran must block a virus-induced, non-TLR4 signal that is required for protection. Mechanistically, we determined that (i) Eritoran blocks high-mobility group B1 (HMGB1)-mediated, TLR4-dependent signaling in vitro and circulating HMGB1 in vivo, and an HMGB1 inhibitor protects against PR8; (ii) Eritoran inhibits pulmonary lung edema associated with ALI; (iii) interleukin (IL)-1β contributes significantly to PR8-induced lethality, as evidenced by partial protection by IL-1 receptor antagonist (IL-1Ra) therapy. Synergistic protection against PR8-induced lethality was achieved when Eritoran and the antiviral drug oseltamivir were administered starting 4 days post infection. Eritoran treatment does not prevent development of an adaptive immune response to subsequent PR8 challenge. Overall, our data support the potential of a host-targeted therapeutic approach to influenza infection.Mucosal Immunology advance online publication 27 January 2016; doi:10.1038/mi.2015.141.

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The ability to sensitively care for others’ wellbeing develops early in ontogeny and is an important developmental milestone for healthy social, emotional, and moral development. One facet of care for others, prosocial comforting, has been linked with important social outcomes such as peer acceptance and friendship quality, underscoring the importance of determining factors involved in the ability to comfort. Although social support has been linked with a number of important social outcomes, no study has directly examined whether felt social support can foster children’s positive behavior toward others. The purpose of the current investigation was to use an experimental priming paradigm to demonstrate that felt social support a) enhances children’s ability to respond prosocially to the distress of others and b) decreases children’s expressions of personal distress when faced with the distress of another person. Participants were 94 4-year-old children (M = 53.56 months, SD = 3.38 months; 52 girls). Children were randomly assigned to either view pictures of mothers and children in close, personal interactions (supportive social interaction condition), happy women and children in separate pictures, presented side-by-side (happy control condition), or pictures of colorful overlapping shapes (neutral control condition). Each set of 20 pictures was presented in the context of a categorization computer game that participants played 4 times throughout the course of the study. Immediately following the first three computer games, children were given the opportunity to comfort someone who was distressed; twice it was the adult experimenter working with the child, and once it was an unseen infant crying over a monitor that participants had been trained to use. Comforting behaviors and distress/arousal were coded in 10-second time segments and yielded a global comforting score and a distress proportion score for each task. Results indicated that priming condition had no effect on either prosocial comforting behavior or expressions of personal distress. I discuss these null findings in light of the available literatures on priming mental representations in children and on prosocial comforting, and suggest some future directions for continued investigation in both fields.

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Early life stages of many marine organisms are being challenged by climate change, but little is known about their capacity to tolerate future ocean conditions. Here we investigated a comprehensive set of biological responses of larvae of two commercially important teleost fishes, Sparus aurata (gilthead seabream) and Argyrosomus regius (meagre), after exposure to future predictions of ocean warming (+4 °C) and acidification (ΔpH= 0.5). The combined effect of warming and hypercapnia elicited a decrease in the hatching success (by 26.4 and 14.3 % for S. aurata and A. regius, respectively) and larval survival (by half) in both species. The length for newly-hatched larvae was not significantly affected, but a significant effect of hypercapnia was found on larval growth. However, while S. aurata growth was reduced (24.8–36.4 % lower), A. regius growth slightly increased (3.2–12.9 % higher) under such condition. Under acidification, larvae of both species spent less time swimming, and displayed reduced attack and capture rates of prey. The impact of warming on these behavioural traits was opposite but less evident. While not studied in A. regius, the incidence of body malformations in S. aurata larvae increased significantly (more than tripled) under warmer and hypercapnic conditions. These morphological impairments and behavioural changes are expected to affect larval performance and recruitment success, and further influence the abundance of fish stocks and the population structure of these commercially important fish species. However, given the pace of ocean climate change, it is important not to forget that species may have the opportunity to acclimate and adapt.

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Since 2008, massive mortality events of Pacific oysters (Crassostrea gigas) have been reported worldwide and these disease events are often associated with Ostreid herpesvirus type 1 (OsHV-1). Epidemiological field studies have also reported oyster age and other pathogens of the Vibrio genus are contributing factors to this syndrome. We undertook a controlled laboratory experiment to simultaneously investigate survival and immunological response of juvenile and adult C. gigas at different time-points post-infection with OsHV-1, Vibrio tasmaniensis LGP32 and V. aestuarianus. Our data corroborates epidemiological studies that juveniles are more susceptible to OsHV-1, whereas adults are more susceptible to Vibrio. We measured the expression of 102 immune-genes by high-throughput RT-qPCR, which revealed oysters have different transcriptional responses to OsHV-1 and Vibrio. The transcriptional response in the early stages of OsHV-1 infection involved genes related to apoptosis and the interferon-pathway. Transcriptional response to Vibrio infection involved antimicrobial peptides, heat shock proteins and galectins. Interestingly, oysters in the later stages of OsHV-1 infection had a transcriptional response that resembled an antibacterial response, which is suggestive of the oyster's microbiome causing secondary infections (dysbiosis-driven pathology). This study provides molecular evidence that oysters can mount distinct immune response to viral and bacterial pathogens and these responses differ depending on the age of the host.