Genetic Analysis of a Rat Model of Aerobic Capacity and Metabolic Fitness

Aerobic capacity is a strong predictor of all-cause mortality and can influence many complex traits. To explore the biological basis underlying this connection, we developed via artificial selection two rat lines that diverge for intrinsic (i.e. inborn) aerobic capacity and differ in risk for complex disease traits. Here we conduct the first in-depth pedigree and molecular genetic analysis of these lines, the high capacity runners (HCR) and low capacity runners (LCR). Our results show that both HCR and LCR lines maintain considerable narrow-sense heritability (h²) for the running capacity phenotype over 28 generations (h² = 0.47 ± 0.02 and 0.43 ± 0.02, respectively). To minimize inbreeding, the lines were maintained by rotational mating. Pedigree records predict that the inbreeding coefficient increases at a rate of <1% per generation, ~37-38% slower than expected for random mating. Genome-wide 10K SNP genotype data for generations 5, 14, and 26 demonstrate substantial genomic evolution: between-line differentiation increased progressively, while within-line diversity deceased. Genome-wide average heterozygosity decreased at a rate of <1% per generation, consistent with pedigree-based predictions and confirming the effectiveness of rotational breeding. Linkage disequilibrium index r² decreases to 0.3 at ~3 Mb, suggesting that the resolution for mapping quantitative trait loci (QTL) can be as high as 2-3 cM. To establish a test population for QTL mapping, we conducted an HCR-LCR intercross. Running capacity of the F1 population (n=176) was intermediate of the HCR and LCR parentals (28 pairs); and the F2 population (n=645) showed a wider range of phenotypic distribution. Importantly, heritability in the F0-F2 pedigree remained high (h²~0.6). These results suggest that the HCR-LCR lines can serve as a valuable system for studying genomic evolution, and a powerful resource for mapping QTL for a host of characters relevant to human health.     

Retracted: Tusk shells in trouble? Physiology and behavior in response to changing temperature in a scaphopod (Mollusca: Scaphopoda: Dentaliida)

Scaphopods (tusk shells) are infaunal marine predators that occur at locally high densities in coastal and deep‐sea mud habitats, and as consumers of foraminifera they are important in carbon cycling. We investigated oxygen metabolism and burying behavior of the scaphopod Rhabdus rectius and its responses to altered temperatures. These are the first measurements of oxygen uptake rates for any member of this taxonomic class. In response to elevated temperatures, oxygen uptake rates increased, but the ability of animals to bury themselves in sediment was compromised. Female scaphopods were significantly larger than males and, when corrected for body mass, oxygen uptake rates were consistently higher for female individuals than for males. This is consistent with previous anecdotal observations of females in other scaphopod species being larger and potentially more active. In conditions of declining oxygen availability, individuals of Rhabdus rectius showed strong oxyregulatory ability by maintaining the same oxygen uptake rate displayed in normoxic conditions. The ability to maintain normal metabolic functioning even in conditions of oxygen limitation would benefit a species living in a benthic environment that may be prone to temporary or transient anoxic events. Yet the decrease in normal escape response in moderately elevated temperatures indicates these animals may be at risk from rising sea temperatures.     

Social perspectives on the use of reference conditions in restoration of fire‐adapted forest landscapes

As approaches to ecological restoration become increasingly large scale and collaborative, there is a need to better understand social aspects of restoration and how they influence land management. In this article, we examine social perspectives that influence the determination of ecological reference conditions in restoration. Our analysis is based on in‐depth interviews with diverse stakeholders involved in collaborative restoration of fire‐adapted forest landscapes. We conducted interviews with 86 respondents from six forest collaboratives that are part of the U.S. Forest Service's Collaborative Forest Landscape Restoration Program. Collaboratives use a variety of approaches to develop reference conditions, including historic, contemporary, and future scenarios. Historical conditions prior to European settlement (nineteenth century or “pre‐settlement” conditions), or prior to more recent grazing, logging, and exclusion of fire, were the predominant type of reference used in all sites. Stakeholders described benefits and limitations of reference conditions. Primary benefits include (1) providing a science‐based framework for bringing stakeholders together around a common vision; (2) gaining social understanding and acceptance of the underlying need for restoration; and (3) serving to neutralize otherwise value‐laden discussions about multiple, sometimes competing, resource objectives. Limitations stem from (1) concerns over social conflict when reference conditions are perceived to contradict other stakeholder values and interests, (2) differing interpretations of reference condition science, (3) inappropriate application or over‐generalization of reference information, and (4) limited relevance of historical references for current and future conditions in some ecosystems. At the same time, collaboratives are adopting innovative strategies to address conceptual and methodological limitations of reference conditions.     

Pyridopyrimidine based cannabinoid-1 receptor inverse agonists: Synthesis and biological evaluation

The synthesis, SAR and binding affinities are described for cannabinoid-1 receptor (CB1R) specific inverse agonists based on pyridopyrimidine and heterotricyclic scaffolds. Food intake and pharmacokinetic evaluation of several of these compounds indicate that they are effective orally active modulators of CB1R.     

Context-Dependent Links between Song Production and Opioid-Mediated Analgesia in Male European Starlings (Sturnus vulgaris)

Little is known about the neural mechanisms that ensure appropriate vocal behaviors within specific social contexts. Male songbirds produce spontaneous (undirected) songs as well as female-directed courtship songs. Opioid neuropeptide activity in specific brain regions is rewarding, at least in mammals, and past studies suggest that the opioid met-enkephalin in such areas is more tightly linked to undirected than female-directed song. Recent data using a song-associated place preference paradigm further suggest that production of undirected but not directed song is tightly linked to intrinsic reward. Opioids have analgesic properties. Therefore, if production of undirected song is closely linked to opioid-mediated reward, the production of undirected but not directed song should be associated with analgesia. Consistent with this prediction, in male starlings we identified a positive correlation between analgesia (decreased reactivity to a hot water bath) and undirected song (in non-breeding season condition males in affiliative flocks) but not female-directed song (in breeding season condition males presented with females). When breeding condition males were divided according to social status, a negative correlation was found in subordinate males (i.e. males that failed to acquire a nest box). These data are consistent with the hypotheses 1) that the production of undirected song is facilitated or maintained by opioids (and/or other neuromodulators that also induce analgesia) and 2) that production of female-directed song is not linked in the same way to release of the same neuromodulators. Results also demonstrate a link between analgesia and song in subordinate individuals lacking a nesting territory within the breeding season. Overall, the findings indicate that distinct neural mechanisms regulate communication in different social contexts and support the working hypothesis that undirected but not directed song is tightly linked to opioid release.     

The biostratigraphic and palaeoenvironmental significance of Lower Cambrian (Botomian) trilobites from the Ak-Kaya section of the Altai Mountains (southern Siberia,Russia)

The presence of one of the oldest records of polycystine Radiolaria in the Lower Cambrian sedimentary sequence of the Ak-Kaya section (Gorny Altai) requires a biostratigraphic dating. The trilobites found recently a few tens of meters below the radiolarian-bearing level belong to Calodiscus resimus Repina, Serrodiscus fossuliferus Repina and Alacephalus aff. contortus Repina; they suggest that this part of the Shashkunar Formation can be correlated with the lower part of the Botomian stage. The absence of eyes in the two former species suggests a mode of life buried in the fine pelagic sediments. Indications of the presence of a strongly developed musculature on the third species point to a palaeoenvironment characterized by a relatively high hydrodynamic regime.     

Regulation of Adherence and Virulence by the Entamoeba histolytica Lectin Cytoplasmic Domain, Which Contains a β2 Integrin Motif

Killing of human cells by the parasite Entamoeba histolytica requires adherence via an amebic cell surface lectin. Lectin activity in the parasite is regulated by inside-out signaling. The lectin cytoplasmic domain has sequence identity with a region of the β2 integrin cytoplasmic tail implicated in regulation of integrin-mediated adhesion. Intracellular expression of a fusion protein containing the cytoplasmic domain of the lectin has a dominant negative effect on extracellular lectin-mediated cell adherence. Mutation of the integrin-like sequence abrogates the dominant negative effect. Amebae expressing the dominant negative mutant are less virulent in an animal model of amebiasis. These results suggest that inside-out signaling via the lectin cytoplasmic domain may control the extracellular adhesive activity of the amebic lectin and provide in vivo demonstration of the lectin’s role in virulence.     

Comparison of Point-of-Use Technologies for Emergency Disinfection of Sewage-Contaminated Drinking Water

Four point-of-use disinfection technologies for treating sewage-contaminated well water were compared. Three systems, based on flocculant-disinfectant packets and N-halamine chlorine and bromine contact disinfectants, provided a range of 4.0 to >6.6 log₁₀ reductions (LR) of naturally occurring fecal indicator and heterotrophic bacteria and a range of 0.9 to >1.9 LR of coliphage.Disasters and flooding can overwhelm sanitation infrastructure, leading to sewage contamination of potable waters. This may be routine during the wet season in many parts of the world and spreads numerous waterborne diseases (21). Point-of-use (POU) water treatment has reduced the incidence of diarrheal disease when used for household drinking water (3, 4, 6, 13) and is now being promoted for disaster relief. While POU systems have recently been reviewed (14), to our knowledge there has been no direct, experimental comparison for treating actual sewage-contaminated waters. In this study, the efficacies of four POU disinfection systems (based on sodium dichloroisocyanurate [NaDCC] tablets, a flocculent-disinfectant powder, and chlorine and bromine contact disinfectant cartridges) in reducing the concentrations of six microbial indicators in well water contaminated with raw sewage were compared.The NaDCC tablets (67 mg; Aquatabs; Medentech, Wexford, Ireland), used for disinfection in low-turbidity water, have shown preliminary efficacy for routine household drinking water treatment (3, 4). The flocculant-disinfectant packet (4 g; PUR; Procter & Gamble Co., Cincinnati, OH) includes Fe₂(SO₄)₃, bentonite, Na₂CO₃, chitosan, polyacrylamide, KMnO₄, and Ca(OCl)₂ (13). It achieved >7.3 log₁₀ reductions (LR) of 24 bacteria species; >4.6 LR of poliovirus and rotavirus in EPA no. 2 test water (turbidity, >30 nephelometric turbidity units [NTU]) (15); and reduced diarrheal illness in Guatemala, Liberia, Kenya, and Pakistan (6, 7, 11, 13).HaloPure canisters (Eureka Forbes, Mumbai, India) contain N-halamine polymer disinfectant beads, poly[1,2-dichloro-5-methyl-5-(4′-vinylphenyl)hydrantoin] for chlorine canisters, and poly[1,2-dibromo-5-methyl-5-(4′-vinylphenyl)hydrantoin] for bromine canisters. Seeded laboratory trials achieved >6.8 LR for Escherichia coli and Staphylococcus aureus as water was passed through the canisters (2). The Cl-contact (producing residuals ranging from 0 to 0.6 mg/liter) and Br-contact (with residuals of 0.68 to 1.8 mg/liter) disinfectants achieved 2.9 LR and 5.0 LR of the bacteriophage MS2, respectively, and 27.5% and 88.5% reductions of the algal toxin microcystin, respectively (5).Sewage-contaminated water was prepared by mixing 9 liters of potable, nonchlorinated well water (pH 7.8; turbidity, 0.33 NTU; Williamston, MI) with 1 liter of raw sewage (City of East Lansing Wastewater Treatment Plant, MI) with an average pH of 6.6 ± 0.1, a biochemical oxygen demand of 144 ± 36 mg/liter, a concentration of total suspended solids of 146 ± 31 mg/liter, and a turbidity of 132 ± 12 NTU. Three disinfection trials were conducted at room temperature for each POU system on three different days to allow for variance in sewage strength. The turbidities of 1:10 dilutions of raw sewage averaged 7.5 ± 2.0 NTU. Table ​Table11 lists the indicator microorganism concentrations in the influent and effluent for each system.

TABLE 1.

Concentrations of influent and 30-min-effluent microorganisms for POU disinfectant systems treating sewage-contaminated water