Effects of brownification and warming on algal blooms, metabolism and higher trophic levels in productive shallow lake mesocosms

An increase of dissolved organic carbon (DOC) in inland waters has been reported across the northern temperate region but the effects of this on whole lake ecosystems, often combined with other anthropogenic stressors like nutrient inputs and warming, are poorly known. The effects of these changes on different component of the ecosystem were assessed in an experiment using twenty-four large (3000L) outdoor mesocosms simulating shallow lakes. Two different temperature regimes (ambient and ambient +4 °C) combined with three levels of organic matter (OM, added as filtered peaty water), simulating the DOC increase that is predicted to take place over the next 4 to 21 years were used. Neither temperature nor OM had significant effects on net ecosystem production, respiration or gross primary production. Phytoplankton chlorophyll a concentration was not significantly affected by warming, however in summer, autumn and winter it was significantly higher in mesocosms receiving intermediate OM levels (July–Feb DOC concentrations 2–6 mg L−1). Summer cyanobacterial blooms were highest in intermediate, and lowest in the highest OM treatments. OM concentration also influenced total macroinvertebrate abundance which was greater in spring and summer in mesocosms with intermediate and high OM. Fish abundance was not significantly affected by OM concentration, but abundance was greater in ambient (55 fish subsample−1) compared to heated mesocosms (17 fish subsample−1) and maximum abundance occurred two weeks later compared to heated mesocosms. The results suggest that changes in OM may have a greater effect on shallow lakes than temperature and that phytoplankton, especially cyanobacteria, benefit from intermediate OM concentrations, therefore, nuisance algal blooms might increase in relatively clear shallow eutrophic lakes where DOC concentrations increase

Molecular Correlates of Social Dominance: A Novel Role for Ependymin in Aggression

Theoretical and empirical studies have sought to explain the formation and maintenance of social relationships within groups. The resulting dominance hierarchies have significant fitness and survival consequences dependent upon social status. We hypothesised that each position or rank within a group has a distinctive brain gene expression profile that correlates with behavioural phenotype. Furthermore, transitions in rank position should determine which genes shift in expression concurrent with the new dominance status. We used a custom cDNA microarray to profile brain transcript expression in a model species, the rainbow trout, which forms tractable linear hierarchies. Dominant, subdominant and submissive individuals had distinctive transcript profiles with 110 gene probes identified using conservative statistical analyses. By removing the dominant, we characterised the changes in transcript expression in sub-dominant individuals that became dominant demonstrating that the molecular transition occurred within 48 hours. A strong, novel candidate gene, ependymin, which was highly expressed in both the transcript and protein in subdominants relative to dominants, was tested further. Using antibody injection to inactivate ependymin in pairs of dominant and subdominant zebrafish, the subdominant fish exhibited a substantial increase in aggression in parallel with an enhanced competitive ability. This is the first study to characterise the molecular signatures of dominance status within groups and the first to implicate ependymin in control of aggressive behaviour. It also provides evidence for indirect genetic effect models in which genotype/phenotype of an individual is influenced by conspecific interactions within a group. The variation in the molecular profile of each individual within a group may offer a new explanation of intraspecific variation in gene expression within undefined groups of animals and provides new candidates for empirical study

Association of Forced Vital Capacity with the Developmental Gene <i>NCOR2</i>

Background Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. Methods Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 chi

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Context dependent differences in growth of two rainbow trout (Oncorhynchus mykiss) lines selected for divergent stress responsiveness

The relative growth of two lines of rainbow trout (Oncorhynchus mykiss) selectively bred for divergent plasma cortisol responsiveness to a confinement stressor (high-responders, HR; low-responders, LR) was evaluated over two generations (F1, F2), both when reared separately and when reared in co-culture. There was no significant difference in growth between the lines when reared separately. However, when reared in co-culture, the LR line significantly out-performed the HR line in both the F1 and F2 generations. It is likely that these results are related to the divergent behavioural attributes that characterise the HR and LR lines, rather than any differences in physiology. The growth disparity between the lines in co-culture may be linked to the greater degree of competitiveness/aggressiveness exhibited by fish of the LR line relative to those of the HR line, or to another as yet unidentified divergent behavioural trait. The implications of these results for the exploitation of the LR line in aquaculture are discussed

Functional genomics of stress responses in fish

Our understanding of the mechanisms underlying stress responses in fish remains fragmentary. However new insights into these mechanisms and their biological significance have been provided by investigation at the transcriptional level. Microarray technology has allowed the unbiased analysis of the transcriptome, providing a potentially system-wide overview of stress responses. In this review, we present recently published transcriptomic studies on stress responses in fish exposed to a range of environmental, xenobiotic, social, and aquacultural stressors. Overall, these studies highlight the complexity of transcript patients, have identified new genes whose expression is significantly modified after exposure to stressors, and have revealed both common and tissue-specific expression signatures. Some shortcomings can be identified, including lack of information on the longer-term compensatory or adaptive phases of the stress response, limitations on gene annotation, and the use of pooled mRNA preparations, which masks variation between individuals. Nonetheless, although the functional genomic analysis of stress responses in fish is still in its infancy, rapid growth in the number of studies and continued advances in technology and database content will inevitably lead to a fuller understanding of the processes involved and to the identification of novel stress indicators with diagnostic or predictive value

Chemical exposure and stress responses in UK fish - Part 2. Final report

Executive summary: 1. The neuroendocrine stress response is a critically important adaptive mechanism in all vertebrate animals. The response is activated by events or conditions that threaten or challenge the animal (stressors). When triggered, the stress response evokes a range of physiological, endocrinological and behavioural adjustments that collectively increase the animal’s likelihood of survival. A key outcome of the response is a rapid elevation in the concentration of the steroid hormone cortisol in the blood. Measurement of stress-induced cortisol concentrations can be employed as an index of the responsiveness of the stress axis to a stressor. 2. Because the stress response is dependent upon a neuroendocrine signalling cascade it is susceptible to modulation by chemicals that mimic the hormones involved, or interfere with their synthesis or metabolism, or influence hormone-receptor interactions. Interference with the function of the stress axis will compromise the ability of the animal to mount an appropriate response to stressors and can therefore be assumed to have implications for the fitness of the animal. The term fitness in this context means the combination of all those biological processes which confer the ability to survive to reproductive age and produce appropriate numbers of normal offspring. 3. Our field surveys of three-spined stickleback populations in NW England have shown that the magnitude of the stress response, measured as both stress-induced whole-body cortisol concentrations, and the stress-induced release of cortisol to water, varies with exposure to wastewater treatment works (WWTW) effluent. We interpret this as indicating that among the range of contaminants present in WWTW effluent, one or more act to alter the responsiveness of the stress axis by directly interfering with cognitive, biosynthetic, feedback, clearance, or signalling systems. 4. The number of sites in NW England contributing to these findings strongly suggests that modulation of the responsiveness of the stress axis by exposure to WWTW effluent is a widespread phenomenon and will likely be observed at similar sites throughout the UK and elsewhere, and in species of fish in addition to three-spined stickleback. Other aquatic vertebrates are also potentially at risk. 5. At sites with no upstream WWTW input we have previously observed unexplained between-site variation in the responsiveness of the stress axis among sticklebacks. This is shown to be related to variation in a range of physico-chemical water quality determinands. A similar range of water quality determinands is also associated with variation in the stress axis at WWTW-impacted sites. These observations suggest that the modulation of the stress axis of fish is not limited to rivers with identifiable WWTW discharges but is more widespread and encompasses fish in rivers considered to be free from effluent-derived endocrine-active contaminants. 6. Variation in stress responsiveness among fish at sites unaffected by WWTW discharges and at sites downstream of WWTWs is most likely attributable to (i) the presence of unidentified contaminants that occur together with, and in proportion to, water quality indicators and have specific functional effects on the stress axis of fish, or (ii) direct effects of one or more of the core range of water quality indices themselves. For example, nitrate has been shown to disrupt steroidogenesis in fish and our results show inter alia that stress-induced cortisol release in sticklebacks downstream of WWTW discharges was positively correlated with the mean concentration of nitrate in the rivers sampled. Although this is not confirmation of a causal relationship the observation warrants further investigation. 7. Preliminary data describing variation in the abundance of human mtDNA in water samples taken from sites not receiving WWTW effluent suggests that some sites identified as being unaffected by WWTW effluent may nonetheless be exposed to sewage pollution, and presumably therefore chemical contamination associated with sewage, from sources other than documented WWTWs. 8. Variation among water quality determinands, and effluent concentration, explains a large proportion of the variation in size (mass, length) among stickleback populations exposed to WWTW effluent. Most of these relationships are negative, even though it is to be expected that the nutrient inputs from WWTWs would lead to increased growth. Size is a major determinant of fitness in fish and these findings suggest that effluent exposure reduces fitness among fish residing downstream of WWTW discharges. It remains to be established whether the negative effects on size are mediated via contaminant effects on the stress axis, or as a result of direct effects on growth-related processes, or as a reflection of energetic costs associated with adaptive responses to contaminant challenge. 9. Sticklebacks translocated from WWTW effluent-impacted sites to pristine holding conditions retained the level of stress axis reactivity associated with their sites of origin for at least 5 months post-transfer indicating that these effects are not dependent upon acute ongoing exposure to WWTW effluent, or local environmental factors. Instead, variation in stress axis reactivity is a robust trait that may reflect local adaptations at a genetic level, effects of early developmental exposure, or persistent effects on the stress axis arising from epigenetic mechanisms. 10. In summary, this project has revealed previously unsuspected, major and widespread variation in the reactivity of the stress axis of a common freshwater fish species. For fish at sites downstream of WWTW discharges this modulation of the hormonal stress response is explained in part by variation in the concentration of treated sewage effluent to which they are exposed. For fish at sites ostensibly unaffected by WWTW discharges variation in the function of the stress axis is related to variation in a range of physico-chemical indices of water quality. These observations have potentially serious implications for the overall fitness of fish in UK rivers. Furthermore, given the highly conserved nature of hormonal stress responses across all the vertebrates, there may also be implications for other species. We recommend that further work on this subject should be considered, in particular to identify the causative substance(s), and to explore the full implications for the fitness of UK fish populations