Ecoacoustic monitoring of lake sturgeon (Acipenser fulvescens) spawning and its relation to anthropogenic noise

Lake sturgeon (Acipenser fulvescens) are endangered in the Laurentian Great Lakes with increasing binational efforts to establish spawning grounds to aid restoration. While SCUBA surveys can document spawning activity, these are labour-intensive and may disrupt spawning. We used passive acoustic monitoring to quantify spawning sounds of lake sturgeon as a first step to developing remote sensing of sturgeon spawning grounds. Acipenser sp. are known to make a variety of sounds including, “thunders” (aka drums), which have been documented in A. fulvescens during spawning. We quantified drums from a known spawning bed. We recorded 5 different potential sturgeon sounds but only quantified drums as a marker for spawning activity. Drums were low frequency with average frequency peaks at 40 and 92 Hz and a rapid drop-off thereafter. There was no relationship between calling activity and water temperature but calling activity increased as the summer progressed. Call production was most active from 0600 to 1500 h with little calling activity during nighttime recordings. The presence of low frequency boat sounds did correlate with a reduction in maximum calling rate so it is possible that commercial shipping may disrupt sturgeon communication, but more research is necessary to separate correlational from causative effects. These recordings represent a promising approach to map sturgeon spawning activity and show the potential effect of human activity on communication in this threatened species.     

Antiviral TRIMs: friend or foe in autoimmune and autoinflammatory disease?

The concept that viral sensing systems, via their ability to drive pro-inflammatory cytokine and interferon production, contribute to the development of autoimmune and autoinflammatory disease is supported by a wide range of clinical and experimental observations. Recently, the tripartite motif-containing proteins (TRIMs) have emerged as having key roles in antiviral immunity - either as viral restriction factors or as regulators of pathways downstream of viral RNA and DNA sensors, and the inflammasome. Given their involvement in these pathways, we propose that TRIM proteins contribute to the development and pathology of autoimmune and autoinflammatory conditions, thus making them potential novel targets for therapeutic manipulation.     

ISG15 is critical in the control of Chikungunya virus infection independent of UbE1L mediated conjugation

Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L^−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15^−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15^−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection.     

Paternal Genetic Effects on Offspring Swimming Performance Vary with Age of Juvenile Chinook Salmon, Oncorhynchus tshawytscha

While fish swimming behaviour has been extensively studied, the parental genetic basis of this critical behaviour has been rarely examined, especially past the earliest stages of development. We used a quantitative genetic breeding design to measure the critical swimming speed (U-crit) of offspring (15 and 18 weeks post-hatch) from 36 families of Chinook salmon (Oncorhynchus tshawytscha), a species with a nonresource-based mating system. We investigated the roles of dam, sire, and dam × sire on offspring U-crit, and estimated contributions of additive and nonadditive genetic effects and maternal effects to phenotypic variation in U-crit at both ages. We also used existing ‘high-survival’ and ‘low-survival’ lines of Chinook to determine if these two lines show differences in U-crit. At 15 weeks, there were no significant genetic effects, but at 18 weeks there were significant sire effects. Furthermore, additive genetic effects increased from 26 to 100 % from 15 to 18 weeks post-hatch. The two survival lines also showed differences in U-crit at 18 weeks post-hatch, with higher U-crit associated with “high-survival” sires. Collectively, the present study provides evidence for increasing importance of paternal identity (additive genetic variation) on swimming as juvenile offspring age. Given that mortality is high in young Pacific salmon and swimming ability is crucial, the sire effects could potentially shape survival though subsequent developmental stages. The change in the magnitude of effects in the present study indicates that future research should investigate genetic effects across multiple stages for better understanding of how phenotypic traits could respond to selection.     

High-resolution analysis of cis-acting regulatory networks at the α-globin locus

We have combined the circular chromosome conformation capture protocol with high-throughput, genome-wide sequence analysis to characterize the cis-acting regulatory network at a single locus. In contrast to methods which identify large interacting regions (10–1000 kb), the 4C approach provides a comprehensive, high-resolution analysis of a specific locus with the aim of defining, in detail, the cis-regulatory elements controlling a single gene or gene cluster. Using the human α-globin locus as a model, we detected all known local and long-range interactions with this gene cluster. In addition, we identified two interactions with genes located 300 kb (NME4) and 625 kb (FAM173a) from the α-globin cluster.     

Scavenger receptor-A functions in phagocytosis of E. coli by bone marrow dendritic cells

Class-A scavenger receptors (SR-A) are cellular pattern recognition receptors that bind and traffic a variety of endogenous and microbial ligands. However, despite an emerging role for SR-A as a contributor to the innate immune system, little is known of the regulation or function of SR-A on dendritic cells (DCs). Here we show that SR-A expression is upregulated during murine DC differentiation and that SR-A expression levels correlate with the expression of the murine DC marker CD11c. Using bone marrow-derived DCs (BMDCs) from SR-A knockout (SR-A(-/-)) mice, we investigated the contribution of SR-A to BMDC particulate phagocytosis. Functional analyses demonstrated that SR-A is a critical phagocytic receptor for BMDC internalization of the gram-negative bacteria E. coli. SR-A(-/-) BMDCs were impaired in their ability to phagocytose bacteria, and this deficit varied with the bacteria:BMDC cell ratio. Microscopic and biochemical analyses revealed that SR-A is broadly distributed on the surface of BMDCs and is not physically associated with lipid rafts. However, cholesterol depletion demonstrated dependence of SR-A-mediated phagocytosis upon lipid rafts. These data demonstrate a functional contribution for SR-A in the BMDC phagocytic pathway.     

Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence

We have devised a strategy (called recombinase-mediated genomic replacement, RMGR) to allow the replacement of large segments (>100 kb) of the mouse genome with the equivalent human syntenic region. The technique involves modifying a mouse ES cell chromosome and a human BAC by inserting heterotypic lox sites to flank the proposed exchange interval and then using Cre recombinase to achieve segmental exchange. We have demonstrated the feasibility of this approach by replacing the mouse alpha globin regulatory domain with the human syntenic region and generating homozygous mice that produce only human alpha globin chains. Furthermore, modified ES cells can be used iteratively for functional studies, and here, as an example, we have used RMGR to produce an accurate mouse model of human alpha thalassemia. RMGR has general applicability and will overcome limitations inherent in current transgenic technology when studying the expression of human genes and modeling human genetic diseases.     

Modification of chicken avian β-defensin-8 at positively selected amino acid sites enhances specific antimicrobial activity

Antimicrobial peptides (AMPs), essential components of innate immunity, are found in a range of phylogenetically diverse species and are thought to act by disrupting the membrane integrity of microbes. In this paper, we used evolutionary signatures to identify sites that are most relevant during the functional evolution of these molecules and introduced amino acid substitutions to improve activity. We first demonstrate that the anti-microbial activity of chicken avian β-defensin-8, previously known as gallinacin-12, can be significantly increased against Escherichia coli, Listeria monocytogenes, Salmonella typhimurium, Salmonella typhimurium phoP− mutant and Streptococcus pyogenes through targeted amino acid substitutions, which confer increased peptide charge. However, by increasing the AMP charge through amino acid substitutions at sites predicted to be subject to positive selection, antimicrobial activity against Escherichia coli was further increased. In contrast, no further increase in activity was observed against the remaining pathogens. This result suggests that charge-increasing modifications confer increased broad-spectrum activity to an AMP, whilst positive selection at particular sites is involved in directing the antimicrobial response against specific pathogens. Thus, there is potential for the rational design of novel therapeutics based on specifically targeted and modified AMPs. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Population genetics without intraspecific data

A central goal of computational biology is the prediction of phenotype from DNA and protein sequence data. Recent models of sequence change use in silico prediction systems to incorporate the effects of phenotype on evolutionary rates. These models have been designed for analyzing sequence data from different species and have been accompanied by statistical techniques for estimating model parameters when the incorporation of phenotype induces dependent change among sequence positions. A difficulty with these efforts to link phenotype and interspecific evolution is that evolution occurs within populations, and parameters of interspecific models should have population genetic interpretations. We show, with two examples, how population genetic interpretations can be assigned to evolutionary models. The first example considers the impact of RNA secondary structure on sequence change, and the second reflects the tendency for protein tertiary structure to influence nonsynonymous substitution rates. We argue that statistical fit to data should not be the sole criterion for assessing models of sequence change. A good interspecific model should also yield a clear and biologically plausible population genetic interpretation.     

Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition

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