Landscape-scale evaluation of genetic structure among barrier-isolated populations of coastal cutthroat trout, Oncorhynchus clarki clarki

Although the effects of extrinsic barriers to dispersal have increasingly been shown to play a large role in the structuring of contemporary genetic diversity, describing the relationship between landscape structure, stochastic disturbance, and genetic diversity remains a major challenge. Here, environmental features for 27 barrier-isolated populations (2,232 individuals) of coastal cutthroat trout from western Oregon are compared with data from seven microsatellite loci to examine how watershed-scale environmental factors shape genetic diversity. Isolated headwater populations of coastal cutthroat trout are strongly differentiated (mean Fst =0.33) but intrapopulation microsatellite genetic diversity (mean number of alleles per locus = 5, mean He = 0.60) was only moderate. Differences in genetic diversity of fish from the Coast Range (mean alleles = 47) and Cascade Mountains (mean alleles = 30) (P = 0.02) coincided with differences in regional landscape feature. Furthermore, scatter evident from isolation by distance plots within ecoregions indicated that population structure was primarily mediated by gene flow in the Coast Range, but in the Cascade Mountains, genetic drift the dominant factor influencing genetic patterns. Thus through comparisons between landscape structure and genetic diversity we demonstrate an example where physical landscape features play a substantial role in the structuring of genetic diversity

Marine bird aggregations associated with the tidally-driven plume and plume fronts of the Columbia River

Freshwater discharge from large rivers into the coastal ocean creates tidally-driven frontal systems known to enhance mixing, primary production, and secondary production. Many authors suggest that tidal plume fronts increase energy flow to fish-eating predators by attracting planktivorous fishes to feed on plankton aggregated by the fronts. However, few studies of plume fronts directly examine piscivorous predator response to plume fronts. Our work examined densities of piscivorous seabirds relative to the plume region and plume fronts of the Columbia River, USA. Common murres (Uria aalge) and sooty shearwaters (Puffinus griseus) composed 83% of all birds detected on mesoscale surveys of the Washington and Oregon coasts (June 2003-2006), and 91.3% of all birds detected on fine scale surveys of the plume region less than 40 km from the river mouth (May 2003 and 2006). Mesoscale comparisons showed consistently more predators in the central plume area compared to the surrounding marine area (murres: 10.1-21.5 vs. 3.4-8.2 birds km⁻²; shearwaters: 24.2-75.1 vs. 11.8-25.9 birds km⁻²). Fine scale comparisons showed that murre density in 2003 and shearwater density in both 2003 and 2006 were significantly elevated in the tidal plume region composed of the most recently discharged river water. Murres tended to be more abundant on the north face of the plume. In May 2003, more murres and shearwaters were found within 3 km of the front on any given transect, although maximum bird density was not necessarily found in the same location as the front itself. Predator density on a given transect was not correlated with frontal strength in either year. The high bird densities we observed associated with the tidal plume demonstrate that the turbid Columbia River plume does not necessarily provide fish with refuge from visual predators. Bird predation in the plume region may therefore impact early marine survival of Pacific salmon (Oncorhynchus spp.), which must migrate through the tidal plume and plume front to enter the ocean. Because murres and shearwaters eat primarily planktivorous fish such as the northern anchovy (Engraulis mordax), aggregation of these birds in the plume supports the hypothesis that it is the plume region as a whole, and not just the plume fronts, which enhances trophic transfer to piscivorous predators via planktivorous fishes.Keywords: Marine birds, River plumes, USA, Tidal fronts, Columbia River, Predator prey interactions, Forage fish, Salmon, Washington, Orego

Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in a mouse model of retinal vein occlusion

PurposeRetinal vein occlusion (RVO) is a sight-threatening condition typically treated with intravitreal injection of vascular endothelial growth factor (VEGF) antagonists. Treatment response to anti-VEGF therapies is highly variable, with poor visual outcomes and treatment response in patients with significant retinal nonperfusion following RVO. Recently, caspase-9 has been identified as a potent regulator of edema, gliosis, and neuronal dysfunction during acute retinal hypoxia. The purpose of this study was to compare the therapeutic effect of caspase-9 inhibition against VEGF-neutralization in an established mouse model of RVO.MethodsAdult male C57Bl/6 J mice were randomized to induction of RVO and treatment with either vehicle, intravitreal injection of anti-VEGF antibody, topical administration of a selective caspase-9 inhibitor (Pen1-XBir3), or a combination therapy. Animals were followed on days 1, 2, and 8 after RVO with fundus retinal imaging, and with optical coherence tomography (OCT) to capture retinal swelling, capillary nonperfusion (measured by disorganization of retinal inner layers, DRIL), hyperreflective foci (HRF), and retinal atrophy. Focal electroretinography (ERG) measurements were performed on day 7. Histology was performed on retinal sections from day 8.ResultsBoth VEGF neutralization and caspase-9 inhibition showed significant retinal protection from RVO compared to vehicle treatment arm. Retinal reperfusion of occluded veins was accelerated in eyes receiving caspase-9 inhibitor, but not significantly different from vehicle in the anti-VEGF group. Retinal edema was suppressed in all treatment groups, with approximately 2-fold greater edema reduction with caspase-9 inhibition compared to VEGF neutralization. HRF were reduced similarly across all treatment groups compared to vehicle. Retinal detachment was reduced only in eyes treated with caspase-9 inhibitor monotherapy. Caspase-9 inhibition reduced retinal atrophy and preserved ERG response; VEGF neutralization did not prevent neurodegeneration following RVO.ConclusionCaspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in the mouse laser-induced model of RVO

Fishery-specific solutions to seabird bycatch in the U.S. West Coast sablefish fishery

Bird scaring lines (BSLs) protect longline fishing gear from seabird attacks, save bait, reduce incidental seabird mortality and are the most commonly prescribed seabird bycatch mitigation measure worldwide. We collaborated with fishermen to assess the efficacy of applying BSL regulations from the demersal longline sablefish fishery in Alaska to a similar fishery along the U.S West Coast. In contrast to Alaska, some U.S. West Coast vessels use floats along the line to keep hooks off the seafloor, where scavengers degrade the bait and the target catch. Our results confirmed that BSL regulations from Alaska were sufficient to protect baits from bird attacks on longlines without floats, but not baits on longlines with floats. Longlines with floats sank below the reach of albatrosses (2 m depth) at a distance astern (157.7 m ± 44.8 95% CI) that was 2.3 times farther than longlines without floats (68.8 m ± 37.8 95% CI). The floated longline distance was well beyond the protection afforded by BSLs, which is approximately 40 m of aerial extent. Black-footed albatross attacked floated longlines at rates ten times more (2.7 attacks/1000 hooks, 0.48–4.45 95%CI) than longlines without floats (0.20 attacks/1000 hooks, 0.01–0.36 95% CI). Retrospective analysis of NOAA Fisheries Groundfish Observer Program data suggested that seabird bycatch occurs in a few sablefish longline fishing sectors and a minority of vessels, but is not confined to larger vessels. Analysis also confirmed fishermen testimonials that night setting reduced albatross bycatch by an order of magnitude compared to daytime setting, without reducing target catch. Night setting could be an effective albatross bycatch prevention practice if applied to the U.S. West Coast sablefish longline fishery and provide a practical alternative for vessels that elect to use floated longlines. These results highlight the importance of understanding region-specific longline gear modifications to identify effective bycatch reduction tools and the value of working collaboratively with fishermen to craft solutions

Bee‑safe peptidomimetic acaricides achieved by comparative genomics

The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey beesafe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa miteselective acaricides, hence, expedited translational processes

Intranasal Delivery of Caspase-9 Inhibitor Reduces Caspase-6-Dependent Axon/Neuron Loss and Improves Neurological Function after Stroke

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.C.M.T.wassupported bythe American Heart Association and National Institutes of Health (NIH)GrantsNS035933 and NS43089. G.S.S. and S.J.S. were supported by NIH Grant CA69381. E.S.C. was supported by NIH Grant NS40409.Peer reviewe

AglH, a thermophilic UDP‑<i>N</i>‑acetylglucosamine‑1‑phosphate:dolichyl phosphate GlcNAc‑1‑phosphotransferase initiating protein<i> N</i>‑glycosylation pathway in <i>Sulfolobus acidocaldarius</i>, is capable of complementing the eukaryal Alg7

AglH, a predicted UDP-GlcNAc-1-phosphate:dolichyl phosphate GlcNAc-1-phosphotransferase, is initiating the protein N-glycosylation pathway in the thermoacidophilic crenarchaeon Sulfolobus acidocaldarius. AglH successfully replaced the endogenous GlcNAc-1-phosphotransferase activity of Alg7 in a conditional lethal Saccharomyces cerevisiae strain, in which the first step of the eukaryal protein N-glycosylation process was repressed. This study is one of the few examples of cross-domain complementation demonstrating a conserved polyprenyl phosphate transferase reaction within the eukaryal and archaeal domain like it was demonstrated for Methanococcus voltae (Shams-Eldin et al. 2008). The topology prediction and the alignment of the AglH membrane protein with GlcNAc-1-phosphotransferases from the three domains of life show significant conservation of amino acids within the different proposed cytoplasmic loops. Alanine mutations of selected conserved amino acids in the putative cytoplasmic loops II (D(100)), IV (F(220)) and V (F(264)) demonstrated the importance of these amino acids for cross-domain AlgH activity in in vitro complementation assays in S. cerevisiae. Furthermore, antibiotic treatment interfering directly with the activity of dolichyl phosphate GlcNAc-1-phosphotransferases confirmed the essentiality of N-glycosylation for cell survival

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead